Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00633893
Collaborator
Pfizer (Industry)
2,711
429
3
51
6.3
0.1
Study Details
Study Description
Brief Summary
The purpose is to evaluate the effects of an investigational blood thinner, apixaban, in preventing venous thromboembolic (VTE) recurrence or death in patients who have completed their intended treatment for deep vein thrombosis (DVT) or pulmonary embolism (PE)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2711 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Safety and Efficacy Trial Evaluating the Use of Apixaban for the Extended Treatment of Deep Vein Thrombosis and Pulmonary Embolism
Study Start Date
:
May 1, 2008
Actual Primary Completion Date
:
Aug 1, 2012
Actual Study Completion Date
:
Aug 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 2.5 mg |
Drug: Apixaban
Tablets, Oral, twice daily, 12 months
Other Names:
|
| Experimental: 2 5.0 mg |
Drug: Apixaban
Tablets, Oral, twice daily, 12 months
Other Names:
|
| Active Comparator: 3 0 mg |
Drug: Placebo
Tablets, Oral, twice daily, 12 months
|
Outcome Measures
Primary Outcome Measures
- Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
- Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 months]
VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
Secondary Outcome Measures
- Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
- Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event.
- Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
- Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
- Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation).
- Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
- Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation [Day 1 up to 12 Months]
DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
- Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation [Day 1 up to 12 Months]
All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
- Adjudicated Major Bleeding During the Treatment Period - Treated Population [Day 1 up to 12 Months]
Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
- Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants [Day 1 up to 12 Months]
Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
- Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants [Day 1 up to 12 months]
Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
- Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants [Day 1 up to 12 months]
All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
- Adjudicated Total Bleeding During the Treatment Period - Treated Participants [Day 1 up to 12 months]
All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
- Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints.
- Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
- Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
- Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
- Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint.
- Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
- Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation [Day 1 up to 12 Months]
DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women ≥ 18 years of age;
-
Clinical diagnosis of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE);
-
Anticoagulant treatment completed
-
No recurrence of Venous Thromboembolism (VTE)
Exclusion Criteria:
-
Subjects with indications for long-term treatment with a vitamin K antagonist
-
Active bleeding or high risk for serious bleeding
-
Short life expectancy
-
Uncontrolled high blood pressure
-
Impaired kidney or liver function
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alabama Clinical Therapeutics, Llc | Birmingham | Alabama | United States | 35235 |
| 2 | Cardiovascular Consultants, Ltd. | Phoenix | Arizona | United States | 85032 |
| 3 | Robert J. Bloomberg, Md, Pc | Tempe | Arizona | United States | 85283 |
| 4 | Fort Smith Lung Center | Fort Smith | Arkansas | United States | 72901 |
| 5 | Beaver Medical Group | Banning | California | United States | 92220 |
| 6 | Scripps Clinic/Scripps Health And Green Hospital | La Jolla | California | United States | 92037 |
| 7 | Healthcare Partners Medical Group | Los Angeles | California | United States | 90015 |
| 8 | Mission Internal Medical Group | Mission Viejo | California | United States | 92691 |
| 9 | Desert Med Grp Inc, Dba Desert Oasis Healthcare Med Group | Palm Springs | California | United States | 92262 |
| 10 | Indus Clinical Research Institute, Inc. | Pomona | California | United States | 91767 |
| 11 | Kaiser Permanente Medical Center | San Francisco | California | United States | 94118 |
| 12 | Stanford University Medical Center | Stanford | California | United States | 94305 |
| 13 | Harbor Ucla Medical Center | Torrance | California | United States | 90509 |
| 14 | Progressive Clinical Research | Vista | California | United States | 92083 |
| 15 | Rocky Mountain Internal Medicine | Aurora | Colorado | United States | 80012 |
| 16 | New West Physicians | Golden | Colorado | United States | 80401 |
| 17 | Alfieri Cardiology | Newark | Delaware | United States | 19713 |
| 18 | Bay Pines Va Healthcare Systems | Bay Pines | Florida | United States | 33744 |
| 19 | Research Alliance, Inc. | Clearwater | Florida | United States | 33756 |
| 20 | St. Francis Sleep Allergy & Lung Institute | Clearwater | Florida | United States | 33765 |
| 21 | Berma Research Group | Fort Lauderdale | Florida | United States | 33316 |
| 22 | Healthworx | Hollywood | Florida | United States | 33021 |
| 23 | Hematology Oncology Associates | Loxahatchee | Florida | United States | 33470 |
| 24 | South Miami Heart Center | Miami | Florida | United States | 33143 |
| 25 | Physicians Regional Medical Group | Naples | Florida | United States | 34119 |
| 26 | Richard A. Mclean M.D., P.A. | Plantation | Florida | United States | 33317 |
| 27 | Tampa Clinical Research | Tampa | Florida | United States | 33624 |
| 28 | Primary Care Of The Treasure Coast, Inc. | Vero Beach | Florida | United States | 32960 |
| 29 | Cleveland Clinic Florida | Weston | Florida | United States | 33331 |
| 30 | Vascular Surgical Associates, Pc | Austell | Georgia | United States | 30106 |
| 31 | Atlanta Institute For Medical Research, Inc | Decatur | Georgia | United States | 30030 |
| 32 | Gwinnett Biomedical Research | Lawrenceville | Georgia | United States | 30046 |
| 33 | Boise Orthopedic Clinic | Boise | Idaho | United States | 83706 |
| 34 | Saltzer Medical Group | Nampa | Idaho | United States | 83686 |
| 35 | Infectious Disease Of Indiana Psc | Carmel | Indiana | United States | 46032 |
| 36 | Office Of:Eugene C. Fletcher, Md | New Albany | Indiana | United States | 47150 |
| 37 | Heartland Vascular Medicine And Surgery | Windsor Heights | Iowa | United States | 50324 |
| 38 | Kentucky Lung Clinic | Hazard | Kentucky | United States | 41701 |
| 39 | Owensboro Heart & Vascular | Owensboro | Kentucky | United States | 42303 |
| 40 | Pen Bay Medical Center | Rockport | Maine | United States | 04856 |
| 41 | Anne Arundel Health System Research Institute, Inc. | Annapolis | Maryland | United States | 21401 |
| 42 | Cape Cod Research Institute | Hyannis | Massachusetts | United States | 02601 |
| 43 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 44 | William Beaumont Hospital | Royal Oak | Michigan | United States | 48073 |
| 45 | Veterans Affairs Medical Center | Kansas City | Missouri | United States | 64128 |
| 46 | Mercury Street Medical Group, Pllc | Butte | Montana | United States | 59701 |
| 47 | Great Falls Clinic, Llp | Great Falls | Montana | United States | 59405 |
| 48 | Internal Medical Associates Of Grand Island, P.C | Grand Island | Nebraska | United States | 68803 |
| 49 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131 |
| 50 | Kaleida Health System | Buffalo | New York | United States | 14209 |
| 51 | Goshen Medical Associates | Goshen | New York | United States | 10924 |
| 52 | Sjh Cardiology Associates | Liverpool | New York | United States | 13088 |
| 53 | Richmond University Medical Center | Staten Island | New York | United States | 10310 |
| 54 | New York Medical College | Valhalla | New York | United States | 10595 |
| 55 | Thomas L. Ortel, Md, Phd | Durham | North Carolina | United States | 27710 |
| 56 | Valley Internal Medicine | Fayetteville | North Carolina | United States | 28304 |
| 57 | Rex Healthcare | Raleigh | North Carolina | United States | 27607 |
| 58 | Piedmont Healthcare/Research | Statesville | North Carolina | United States | 28625 |
| 59 | Whiteville Medical Associates, P.A. | Whiteville | North Carolina | United States | 28472 |
| 60 | Wilmington Medical Research | Wilmington | North Carolina | United States | 28401 |
| 61 | Akron General Medical Center | Akron | Ohio | United States | 44307 |
| 62 | Community Health Care, Inc. | Canal Fulton | Ohio | United States | 44614 |
| 63 | Valley Medical Research | Centerville | Ohio | United States | 45459 |
| 64 | Ohio State University Medical Center | Columbus | Ohio | United States | 43210 |
| 65 | Remington Davis Inc. | Columbus | Ohio | United States | 43215 |
| 66 | Jobst Vascular Center At The Toledo Hospital | Toledo | Ohio | United States | 43606 |
| 67 | Cor Clinical Research, Llc | Oklahoma City | Oklahoma | United States | 73103 |
| 68 | Pma Medical Specialists | Phoenixville | Pennsylvania | United States | 19460 |
| 69 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 70 | Charleston Hematology Oncology Associates, Pa | Charleston | South Carolina | United States | 29414 |
| 71 | Greenville Hospital System | Greenville | South Carolina | United States | 29615 |
| 72 | Three Rivers Medical Associates, Pa | Irmo | South Carolina | United States | 29063 |
| 73 | Clinical Research Authority, Llc | Murrells Inlet | South Carolina | United States | 29576 |
| 74 | Palmetto Clinical Research | Summerville | South Carolina | United States | 29485 |
| 75 | Holston Medical Group | Bristol | Tennessee | United States | 37620 |
| 76 | Holston Medical Group | Kingsport | Tennessee | United States | 37660 |
| 77 | Amarillo Heart Clinical Research Institute Inc. | Amarillo | Texas | United States | 79106 |
| 78 | Corsicana Medical Research | Corsicana | Texas | United States | 75110 |
| 79 | Ankur Doshi, Md | Houston | Texas | United States | 77024 |
| 80 | Northwest Heart Center | Tomball | Texas | United States | 77375 |
| 81 | Tanner Clinic | Layton | Utah | United States | 84041 |
| 82 | University Of Utah Hospital | Salt Lake City | Utah | United States | 84132 |
| 83 | University Of Virginia Health System | Charlottesville | Virginia | United States | 22908 |
| 84 | Sentara York Clinical Research | Norfolk | Virginia | United States | 23510 |
| 85 | Lake Washington Vascular, Pllc | Bellevue | Washington | United States | 98004 |
| 86 | Franciscan Research Center | Tacoma | Washington | United States | 98405 |
| 87 | Medical Assoicates Inc. | Menomonee Falls | Wisconsin | United States | 53051 |
| 88 | Local Institution | Capital Federal | Buenos Aires | Argentina | C1426ANZ |
| 89 | Local Institution | Ciudad Autonoma De Buenos Aire | Buenos Aires | Argentina | 1093 AAS |
| 90 | Local Institution | Ciudad Autonoma De Buenos Aire | Buenos Aires | Argentina | C1180AAX |
| 91 | Local Institution | Ciudad Autonoma De Buenos Aire | Buenos Aires | Argentina | C1437JCP |
| 92 | Local Institution | Ciudad De Buenos Aires | Buenos Aires | Argentina | C1034ACO |
| 93 | Local Institution | Ciudad De Buenos Aires | Buenos Aires | Argentina | C1181ACH |
| 94 | Local Institution | Coronel Suarez | Buenos Aires | Argentina | B7540GHD |
| 95 | Local Institution | La Plata | Buenos Aires | Argentina | 1900 |
| 96 | Local Institution | La Plata | Buenos Aires | Argentina | B1902COI |
| 97 | Local Institution | Mar Del Plata | Buenos Aires | Argentina | 7600 |
| 98 | Local Institution | San Martin | Buenos Aires | Argentina | B1650CSQ |
| 99 | Local Institution | Rosario | Santa Fe | Argentina | S2000CVB |
| 100 | Local Institution | Rosario | Santa Fe | Argentina | S2000DSV |
| 101 | Local Institution | Rosario | Santa Fe | Argentina | S2002KDS |
| 102 | Local Institution | Buenos Aires | Argentina | C1122AAL | |
| 103 | Local Institution | Buenos Aires | Argentina | C1280AEB | |
| 104 | Local Institution | Buenos Aires | Argentina | C1431FWO | |
| 105 | Local Institution | Cordoba | Argentina | 5000 | |
| 106 | Local Institution | Cordoba | Argentina | X5000JHQ | |
| 107 | Local Institution | Corrientes | Argentina | 3400 | |
| 108 | Local Institution | Garran | Australian Capital Territory | Australia | 2605 |
| 109 | Local Institution | Kogarah | New South Wales | Australia | 2217 |
| 110 | Local Institution | Lismore | New South Wales | Australia | 2480 |
| 111 | Local Institution | St Leonards | New South Wales | Australia | 2065 |
| 112 | Local Institution | Herston | Queensland | Australia | 4029 |
| 113 | Local Institution | Kippa Ring | Queensland | Australia | 4021 |
| 114 | Local Institution | Woolloongabba | Queensland | Australia | 4102 |
| 115 | Local Institution | Adelaide | South Australia | Australia | 5000 |
| 116 | Local Institution | Bedford Park | South Australia | Australia | 5042 |
| 117 | Local Institution | Launceston | Tasmania | Australia | 7250 |
| 118 | Local Institution | Box Hill | Victoria | Australia | 3128 |
| 119 | Local Institution | Clayton | Victoria | Australia | 3168 |
| 120 | Local Institution | Footscray | Victoria | Australia | 3011 |
| 121 | Local Institution | Parkville | Victoria | Australia | 3050 |
| 122 | Local Institution | Richmond | Victoria | Australia | 3121 |
| 123 | Local Institution | Ringwood East | Victoria | Australia | 3135 |
| 124 | Local Institution | Windsor | Victoria | Australia | 3181 |
| 125 | Local Institution | Perth | Western Australia | Australia | 6000 |
| 126 | Local Institution | Graz | Austria | 8036 | |
| 127 | Local Institution | Innsbruck | Austria | A-6020 | |
| 128 | Local Institution | Vienna | Austria | 1090 | |
| 129 | Local Institution | Vienna | Austria | 1100 | |
| 130 | Local Institution | Wien | Austria | 1090 | |
| 131 | Local Institution | Wien | Austria | 1140 | |
| 132 | Local Institution | Salvador | Bahia | Brazil | 40144 900 |
| 133 | Local Institution | Brasilia | Distrito Federal | Brazil | 70335 |
| 134 | Local Institution | Belo Horizonte - Mg | Minas Gerais | Brazil | 30130 |
| 135 | Local Institution | Belo Horizonte - Mg | Minas Gerais | Brazil | 30150 |
| 136 | Local Institution | Curitiba | Parana | Brazil | 80030 |
| 137 | Local Institution | Curitiba | Parana | Brazil | 80050 |
| 138 | Local Institution | Curitiba | Parana | Brazil | 80810 |
| 139 | Local Institution | Curitiba | Parana | Brazil | 81520 |
| 140 | Local Institution | Rio Janeiro | Rio De Janeiro | Brazil | 22280 |
| 141 | Local Institution | Port Alegre | Rio Grande Do Sul | Brazil | 90020 |
| 142 | Local Institution | Porto Alegre | Rio Grande Do Sul | Brazil | 90035 |
| 143 | Local Institution | Porto Alegre | Rio Grande Do Sul | Brazil | 90610 |
| 144 | Local Institution | Porto Alegre | Rio Grande Do Sul | Brazil | 9110270 |
| 145 | Local Institution | Botucatu | Sao Paulo | Brazil | 18618 |
| 146 | Local Institution | Campinas | Sao Paulo | Brazil | 13083 |
| 147 | Local Institution | Santo Andre - Sp | Sao Paulo | Brazil | 09060 |
| 148 | Local Institution | Sao Jose Do Rio Preto | Sao Paulo | Brazil | 15015 |
| 149 | Local Institution | Sao Jose Do Rio Preto | Sao Paulo | Brazil | 15090 |
| 150 | Local Institution | Rio De Janeiro | Brazil | 20551 | |
| 151 | Local Institution | Sao Paulo | Brazil | 01323 | |
| 152 | Local Institution | Sao Paulo | Brazil | 01509 | |
| 153 | Local Institution | Sao Paulo | Brazil | 04005 | |
| 154 | Local Institution | Sao Paulo | Brazil | 05403 | |
| 155 | Local Institution | Edmonton | Alberta | Canada | T5H 4B9 |
| 156 | Local Institution | Edmonton | Alberta | Canada | T5X 3N5 |
| 157 | Local Institution | Edmonton | Alberta | Canada | Tsa 4l8 |
| 158 | Local Institution | Kelowna | British Columbia | Canada | V1Y 9L8 |
| 159 | Local Institution | Victoria | British Columbia | Canada | V8R 4R2 |
| 160 | Local Institution | Hamilton | Ontario | Canada | L8L 2X2 |
| 161 | Local Institution | Hamilton | Ontario | Canada | L8S 4K1 |
| 162 | Local Institution | Toronto | Ontario | Canada | M5G 2C4 |
| 163 | Local Institution | Waterloo | Ontario | Canada | N2J 1C4 |
| 164 | Local Institution | Windsor | Ontario | Canada | N8X 5A6 |
| 165 | Local Institution | Montreal | Quebec | Canada | H1T 2M4 |
| 166 | Local Institution | Montreal | Quebec | Canada | H3G 1A4 |
| 167 | Local Institution | Montreal | Quebec | Canada | H3T 1M5 |
| 168 | Local Institution | Pointe- Claire | Quebec | Canada | H9R 3J1 |
| 169 | Local Institution | St. Jerome | Quebec | Canada | J7Z 5T3 |
| 170 | Local Institution | Quebec | Canada | G1V 4G5 | |
| 171 | Local Institution | Temuco | Araucania | Chile | 4781173 |
| 172 | Local Institution | Punta Arenas | Magallanes Antartica | Chile | 6212296 |
| 173 | Local Institution | Independencia | Metropolitana | Chile | XXXXX |
| 174 | Local Institution | Santiago | Metropolitana | Chile | 7500520 |
| 175 | Local Institution | Santiago | Metropolitana | Chile | 7600448 |
| 176 | Local Institution | Santiago | Metropolitana | Chile | 7980378 |
| 177 | Local Institution | Santiago | Metropolitana | Chile | 8330024 |
| 178 | Local Institution | Vina Del Mar | Valparaiso | Chile | 2520000 |
| 179 | Local Institution | Kladno | Czech Republic | 272 59 | |
| 180 | Local Institution | Litomysl | Czech Republic | 570 14 | |
| 181 | Local Institution | Mestec Kralove | Czech Republic | 289 03 | |
| 182 | Local Institution | Ostrava Vitkovice | Czech Republic | 703 00 | |
| 183 | Local Institution | Plzen | Czech Republic | 323 33 | |
| 184 | Local Institution | Praha 13 | Czech Republic | 158 00 | |
| 185 | Local Institution | Praha 1 | Czech Republic | 110 00 | |
| 186 | Local Institution | Praha 1 | Czech Republic | 118 33 | |
| 187 | Local Institution | Praha 2 | Czech Republic | 120 00 | |
| 188 | Local Institution | Praha 2 | Czech Republic | 121 11 | |
| 189 | Local Institution | Praha 2 | Czech Republic | 128 08 | |
| 190 | Local Institution | Praha 4 | Czech Republic | 140 21 | |
| 191 | Local Institution | Usti Nad Orlici | Czech Republic | 562 18 | |
| 192 | Local Institution | Arhus C | Denmark | 8000 | |
| 193 | Local Institution | Braedstrup | Denmark | 8740 | |
| 194 | Local Institution | Esbjerg | Denmark | 6700 | |
| 195 | Local Institution | Frederiksberg | Denmark | 2000 | |
| 196 | Local Institution | Hellerup | Denmark | 2900 | |
| 197 | Local Institution | Herning | Denmark | 7400 | |
| 198 | Local Institution | Hilleroed | Denmark | 3400 | |
| 199 | Local Institution | Naestved | Denmark | 4700 | |
| 200 | Local Institution | Silkeborg | Denmark | 8600 | |
| 201 | Local Institution | Arras | France | 62022 | |
| 202 | Local Institution | Besancon | France | 25000 | |
| 203 | Local Institution | Brest Cedex | France | 29609 | |
| 204 | Local Institution | Clamart | France | 92141 | |
| 205 | Local Institution | Clermont-Ferrand Cedex 01 | France | 63003 | |
| 206 | Local Institution | Dijon | France | 21079 | |
| 207 | Local Institution | Grenoble | France | 38043 | |
| 208 | Local Institution | Le Kremlin-Bicetre | France | 94275 | |
| 209 | Local Institution | Lille Cedex | France | 59020 | |
| 210 | Local Institution | Limoges Cedex | France | 87042 | |
| 211 | Local Institution | Lyon Cedex 03 | France | 69437 | |
| 212 | Local Institution | Nantes | France | 44093 | |
| 213 | Local Institution | Saint-Priest En Jarez | France | 42270 | |
| 214 | Local Institution | Toulouse Cedex 9 | France | 31059 | |
| 215 | Local Institution | Vernon | France | 27200 | |
| 216 | Local Institution | Berlin | Germany | 10117 | |
| 217 | Local Institution | Berlin | Germany | 10787 | |
| 218 | Local Institution | Berlin | Germany | 14050 | |
| 219 | Local Institution | Bochum | Germany | 44791 | |
| 220 | Local Institution | Bonn | Germany | 53115 | |
| 221 | Local Institution | Cologne | Germany | 50937 | |
| 222 | Local Institution | Dortmund | Germany | 44137 | |
| 223 | Local Institution | Dresden | Germany | 01067 | |
| 224 | Local Institution | Dresden | Germany | 01307 | |
| 225 | Local Institution | Erfurt | Germany | 99089 | |
| 226 | Local Institution | Frankfurt | Germany | 60596 | |
| 227 | Local Institution | Gottingen | Germany | 37075 | |
| 228 | Local Institution | Karlsbad | Germany | 76307 | |
| 229 | Local Institution | Krefeld | Germany | 47805 | |
| 230 | Local Institution | Ludwigshafen | Germany | 67063 | |
| 231 | Local Institution | Mannheim | Germany | 68161 | |
| 232 | Local Institution | Mannheim | Germany | 68165 | |
| 233 | Local Institution | Mannheim | Germany | 68167 | |
| 234 | Local Institution | Munchen | Germany | 80331 | |
| 235 | Local Institution | Munich | Germany | 80336 | |
| 236 | Local Institution | Hong Kong | Hong Kong | ||
| 237 | Local Institution | Shatin, N.T | Hong Kong | ||
| 238 | Local Institution | Hyderabad | Andhra Pradesh | India | 500 082 |
| 239 | Local Institution | Hyderabad | Andhra Pradesh | India | 500034 |
| 240 | Local Institution | Ahmedabad | Gujarat | India | 380006 |
| 241 | Local Institution | Gurgaon | Haryana | India | 122001 |
| 242 | Local Institution | Bangalore | Karnataka | India | 560054 |
| 243 | Local Institution | Bengaluru | Karnataka | India | 560017 |
| 244 | Local Institution | Kochi | Kerala | India | 682041 |
| 245 | Local Institution | Pune | Maharashtra | India | 411001 |
| 246 | Local Institution | Mohali | Punjab | India | 160062 |
| 247 | Local Institution | Ludhiana | Tagore Nagar | India | 141001 |
| 248 | Local Institution | Chennai | Tamil Nadu | India | 600 006 |
| 249 | Local Institution | Ahmedabad | India | 380015 | |
| 250 | Local Institution | Bangalore, Karnataka | India | 560034 | |
| 251 | Local Institution | Bangalore | India | 560052 | |
| 252 | Local Institution | Chennai | India | 600 003 | |
| 253 | Local Institution | Chennai | India | 600 006 | |
| 254 | Local Institution | New Dehli | India | 110025 | |
| 255 | Local Institution | Afula | Israel | 18101 | |
| 256 | Local Institution | Givataim | Israel | 53488 | |
| 257 | Local Institution | Hadera | Israel | 38101 | |
| 258 | Local Institution | Haifa | Israel | 31048 | |
| 259 | Local Institution | Haifa | Israel | 31096 | |
| 260 | Local Institution | Holon | Israel | 58100 | |
| 261 | Local Institution | Jerusalem | Israel | 91031 | |
| 262 | Local Institution | Kfar Saba | Israel | 44281 | |
| 263 | Local Institution | Kiryat Hadassah | Israel | 91120 | |
| 264 | Local Institution | Nahariya | Israel | 22100 | |
| 265 | Local Institution | Petach-Tikva | Israel | 49100 | |
| 266 | Local Institution | Safed | Israel | 13100 | |
| 267 | Local Institution | Tel Aviv | Israel | 64239 | |
| 268 | Local Institution | Tel Hashomer | Israel | 52621 | |
| 269 | Local Institution | Bollate | Italy | 20021 | |
| 270 | Local Institution | Bologna | Italy | 40138 | |
| 271 | Local Institution | Chieti Scalo | Italy | 66013 | |
| 272 | Local Institution | Cosenza | Italy | 87100 | |
| 273 | Local Institution | Ferrara | Italy | 44100 | |
| 274 | Local Institution | Firenze | Italy | 50134 | |
| 275 | Local Institution | Genova | Italy | 16128 | |
| 276 | Local Institution | Milano | Italy | 20132 | |
| 277 | Local Institution | Padova | Italy | 35128 | |
| 278 | Local Institution | Palermo | Italy | 90127 | |
| 279 | Local Institution | Pavia | Italy | 27100 | |
| 280 | Local Institution | Perugia | Italy | 06132 | |
| 281 | Local Institution | Piacenza | Italy | 29100 | |
| 282 | Local Institution | Pisa | Italy | 56124 | |
| 283 | Local Institution | Roma | Italy | 00168 | |
| 284 | Local Institution | Rozzano (Mi) | Italy | 20089 | |
| 285 | Local Institution | San Daniele Del Friuli (Ud) | Italy | 33038 | |
| 286 | Local Institution | Udine | Italy | 33100 | |
| 287 | Local Institution | Venezia | Italy | 30122 | |
| 288 | Local Institution | Vicenza | Italy | 36100 | |
| 289 | Local Institution | Vittorio Veneto (Tv) | Italy | 31029 | |
| 290 | Local Institution | Busan | Korea, Republic of | 602-702 | |
| 291 | Local Institution | Jongno-Gu | Korea, Republic of | 110-774 | |
| 292 | Local Institution | Seoul | Korea, Republic of | 120752 | |
| 293 | Local Institution | Seoul | Korea, Republic of | 135-710 | |
| 294 | Local Institution | Seoul | Korea, Republic of | 137-040 | |
| 295 | Local Institution | Seoul | Korea, Republic of | 138736 | |
| 296 | Local Institution | Tijuana | Baja California | Mexico | 22500 |
| 297 | Local Institution | Mexico | Distrito Federal | Mexico | 06726 |
| 298 | Local Institution | Leon | Guanajuato | Mexico | 37320 |
| 299 | Local Institution | Guadalajara | Jalisco | Mexico | 44130 |
| 300 | Local Institution | Guadalajara | Jalisco | Mexico | 44200 |
| 301 | Local Institution | Guadalajara | Jalisco | Mexico | 44280 |
| 302 | Local Institution | Zapopan | Jalisco | Mexico | 45200 |
| 303 | Local Institution | Monterrey | Nuevo Leon | Mexico | 64000 |
| 304 | Local Institution | Monterrey | Nuevo Leon | Mexico | 64710 |
| 305 | Local Institution | Culiacan | Sinaloa | Mexico | 80020 |
| 306 | Local Institution | Culiacan | Sinaloa | Mexico | 80230 |
| 307 | Local Institution | Xalapa | Veracruz | Mexico | 91020 |
| 308 | Local Institution | Aguascalientes | Mexico | 20230 | |
| 309 | Local Institution | Chihuahua | Mexico | 31203 | |
| 310 | Local Institution | Durango | Mexico | 34080 | |
| 311 | Local Institution | Puebla | Mexico | 72000 | |
| 312 | Local Institution | Queretaro | Mexico | 76000 | |
| 313 | Local Institution | San Luis Potosi | Mexico | 78200 | |
| 314 | Local Institution | San Luis Potosi | Mexico | 78240 | |
| 315 | Local Institution | Alesund | Norway | 6026 | |
| 316 | Local Institution | Fredrikstad | Norway | 1606 | |
| 317 | Local Institution | Gjettum | Norway | 1346 | |
| 318 | Local Institution | Gjovik | Norway | 2819 | |
| 319 | Local Institution | Hamar | Norway | 2318 | |
| 320 | Local Institution | Oslo | Norway | 0407 | |
| 321 | Local Institution | Cavite | Philippines | 4114 | |
| 322 | Local Institution | Davao City | Philippines | 8000 | |
| 323 | Local Institution | Pasig City | Philippines | 1600 | |
| 324 | Local Institution | Quezon City | Philippines | 1102 | |
| 325 | Local Institution | Arkonska 4 | Poland | 71455 | |
| 326 | Local Institution | Bialystok | Poland | 15-276 | |
| 327 | Local Institution | Bydgoszcz | Poland | 85-168 | |
| 328 | Local Institution | Bydgoszcz | Poland | 85-650 | |
| 329 | Local Institution | Bydgoszcz | Poland | 85-681 | |
| 330 | Local Institution | Gdansk | Poland | 80-803 | |
| 331 | Local Institution | Gdynia | Poland | 81-348 | |
| 332 | Local Institution | Gdynia | Poland | 81-423 | |
| 333 | Local Institution | Lodz | Poland | 90-153 | |
| 334 | Local Institution | Lublin | Poland | 20-081 | |
| 335 | Local Institution | Lublin | Poland | 20-718 | |
| 336 | Local Institution | Poznan | Poland | 61-848 | |
| 337 | Local Institution | Przeworsk | Poland | 37-200 | |
| 338 | Local Institution | Szczecin | Poland | 70-111 | |
| 339 | Local Institution | Tarnobrzeg | Poland | 39-400 | |
| 340 | Local Institution | Warsawa | Poland | 02-776 | |
| 341 | Local Institution | Warsaw | Poland | 01-809 | |
| 342 | Local Institution | Warsaw | Poland | 02-005 | |
| 343 | Local Institution | Warszawa | Poland | 01-138 | |
| 344 | Local Institution | Warszawa | Poland | 02-018 | |
| 345 | Local Institution | Wroclaw | Poland | 51-124 | |
| 346 | Local Institution | Wroclaw | Poland | 53-114 | |
| 347 | Local Institution | Guarda | Portugal | 6301-857 | |
| 348 | Local Institution | Lisboa | Portugal | 1769-001 | |
| 349 | Local Institution | San Juan | Puerto Rico | 00909 | |
| 350 | Local Institution | San Juan | Puerto Rico | 00921 | |
| 351 | Local Institution | Baia Mare | Romania | 430031 | |
| 352 | Local Institution | Bucharest | Romania | 022328 | |
| 353 | Local Institution | Bucharest | Romania | 030171 | |
| 354 | Local Institution | Bucharest | Romania | 050098 | |
| 355 | Local Institution | Targu Mures | Romania | 540136 | |
| 356 | Local Institution | Arkhangelsk | Russian Federation | 163045 | |
| 357 | Local Institution | Kemerovo | Russian Federation | 650002 | |
| 358 | Local Institution | Moscow | Russian Federation | 105077 | |
| 359 | Local Institution | Moscow | Russian Federation | 111539 | |
| 360 | Local Institution | Moscow | Russian Federation | 119049 | |
| 361 | Local Institution | Moscow | Russian Federation | 127473 | |
| 362 | Local Institution | Novosibirsk | Russian Federation | 630055 | |
| 363 | Local Institution | Novosibirsk | Russian Federation | 630090 | |
| 364 | Local Institution | Rostov-On Don | Russian Federation | 344022 | |
| 365 | Local Institution | Ryazan | Russian Federation | 390026 | |
| 366 | Local Institution | Saint Petersburg | Russian Federation | 192242 | |
| 367 | Local Institution | Saint-Petersburg | Russian Federation | 196247 | |
| 368 | Local Institution | Saint-Petersburg | Russian Federation | 199106 | |
| 369 | Local Institution | Samara | Russian Federation | 443010 | |
| 370 | Local Institution | Saratov | Russian Federation | 410012 | |
| 371 | Local Institution | Saratov | Russian Federation | 410028 | |
| 372 | Local Institution | St Petersburg | Russian Federation | 194044 | |
| 373 | Local Institution | Tomsk | Russian Federation | 634012 | |
| 374 | Local Institution | Yaroslavl | Russian Federation | 150062 | |
| 375 | Local Institution | Singapore | Singapore | 169608 | |
| 376 | Local Institution | Singapore | Singapore | 308433 | |
| 377 | Local Institution | Bloemfontein | Free State | South Africa | 9301 |
| 378 | Local Institution | Centurion | Gauteng | South Africa | 0157 |
| 379 | Local Institution | Parktown | Gauteng | South Africa | 2193 |
| 380 | Local Institution | Pretoria | Gauteng | South Africa | 0083 |
| 381 | Local Institution | Pretoria | Gauteng | South Africa | 0084 |
| 382 | Local Institution | Durban | Kwa Zulu Natal | South Africa | 4001 |
| 383 | Local Institution | Pietermaritzburg | Kwa Zulu Natal | South Africa | 3201 |
| 384 | Local Institution | Bellville | Western Cape | South Africa | 7530 |
| 385 | Local Institution | George | Western Cape | South Africa | 6529 |
| 386 | Local Institution | Somerset West | Western Cape | South Africa | 7130 |
| 387 | Local Institution | Worcester | Western Cape | South Africa | 6850 |
| 388 | Local Institution | Torrevieja | Alicante | Spain | 03186 |
| 389 | Local Institution | Badalona | Barcelona | Spain | 08916 |
| 390 | Local Institution | Majadahonda | Madrid | Spain | 28222 |
| 391 | Local Institution | San Sebastian De Los Reyes | Madrid | Spain | 28702 |
| 392 | Local Institution | Cadiz | Spain | 11009 | |
| 393 | Local Institution | Getafe | Spain | 28905 | |
| 394 | Local Institution | Girona | Spain | 17007 | |
| 395 | Local Institution | L'Hospitalet De Llobregat | Spain | 08907 | |
| 396 | Local Institution | Leon | Spain | 24008 | |
| 397 | Local Institution | Madrid | Spain | 28007 | |
| 398 | Local Institution | Madrid | Spain | 28029 | |
| 399 | Local Institution | Madrid | Spain | 28040 | |
| 400 | Local Institution | Madrid | Spain | 28041 | |
| 401 | Local Institution | Mourente | Spain | 36071 | |
| 402 | Local Institution | Pamplona | Spain | 31008 | |
| 403 | Local Institution | Salamanca | Spain | 37007 | |
| 404 | Local Institution | Sant Boi De Llobregat | Spain | 08830 | |
| 405 | Local Institution | Tarragona | Spain | 43007 | |
| 406 | Local Institution | Toledo | Spain | 45071 | |
| 407 | Local Institution | Valencia | Spain | 46026 | |
| 408 | Local Institution | Chernihiv | Ukraine | 14034 | |
| 409 | Local Institution | Dnipropetrovsk | Ukraine | 49000 | |
| 410 | Local Institution | Donetsk | Ukraine | 83045 | |
| 411 | Local Institution | Ivano-Frankivsk | Ukraine | 76008 | |
| 412 | Local Institution | Ivano-Frankivsk | Ukraine | 76018 | |
| 413 | Local Institution | Kharkiv | Ukraine | 61018 | |
| 414 | Local Institution | Kyiv | Ukraine | 03680 | |
| 415 | Local Institution | Lviv | Ukraine | 79010 | |
| 416 | Local Institution | Odesa | Ukraine | 65117 | |
| 417 | Local Institution | Ternopil | Ukraine | 46000 | |
| 418 | Local Institution | Vinnytsia | Ukraine | 21018 | |
| 419 | Local Institution | Zaporizhzhia | Ukraine | 69035 | |
| 420 | Local Institution | Aberdeen | Aberdeenshire | United Kingdom | AB25 2ZN |
| 421 | Local Institution | Romford | Essex | United Kingdom | RM7 0AG |
| 422 | Local Institution | London | Greater London | United Kingdom | SE5 9RS |
| 423 | Local Institution | London | Greater London | United Kingdom | SW17 0QT |
| 424 | Local Institution | Manchester | Greater Manchester | United Kingdom | M23 9LT |
| 425 | Local Institution | Hull | Humberside | United Kingdom | HU3 2JZ |
| 426 | Local Institution | Nottingham | Nottinghamshire | United Kingdom | NG7 2UH |
| 427 | Local Institution | Bury St. Edmunds | Suffolk | United Kingdom | IP30 9QU |
| 428 | Local Institution | Coventry | West Midlands | United Kingdom | CV2 2DX |
| 429 | Local Institution | Dudley | West Midlands | United Kingdom | DY1 2HQ |
Sponsors and Collaborators
- Bristol-Myers Squibb
- Pfizer
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00633893
Other Study ID Numbers:
- CV185-057
- EUDRACT: 2007-004953-27
First Posted:
Mar 12, 2008
Last Update Posted:
Nov 25, 2013
Last Verified:
Oct 1, 2013
Study Results
Participant Flow
| Recruitment Details | First participant, first visit: 16 May 2008; Last participant, last visit: 24 August 2012. |
|---|---|
| Pre-assignment Detail | 2711 enrolled/2482 randomized: 133 did not meet inclusion, exclusion criteria; 48 withdrew consent; 8 non-compliance; 3 each administrative and clinical reasons; 2 lost to follow up; 1 death; 1 adverse event (AE), 30 other. Data from 4 participants in site 0650 not analyzed/included in randomized population because source for data not confirmed. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban twice a day (BID) | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Period Title: Overall Study | |||
| STARTED | 840 | 813 | 829 |
| COMPLETED | 726 | 684 | 641 |
| NOT COMPLETED | 114 | 129 | 188 |
Baseline Characteristics
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. | Total of all reporting groups |
| Overall Participants | 840 | 813 | 829 | 2482 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
56.6
(15.3)
|
56.4
(15.6)
|
57.1
(15.2)
|
56.7
(15.4)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
353
42%
|
344
42.3%
|
361
43.5%
|
1058
42.6%
|
| Male |
487
58%
|
469
57.7%
|
468
56.5%
|
1424
57.4%
|
| Region of Enrollment (participants) [Number] | ||||
| Portugal |
1
0.1%
|
1
0.1%
|
0
0%
|
2
0.1%
|
| United States |
88
10.5%
|
75
9.2%
|
96
11.6%
|
259
10.4%
|
| Philippines |
5
0.6%
|
3
0.4%
|
3
0.4%
|
11
0.4%
|
| Hong Kong |
4
0.5%
|
3
0.4%
|
4
0.5%
|
11
0.4%
|
| Spain |
27
3.2%
|
25
3.1%
|
26
3.1%
|
78
3.1%
|
| Ukraine |
87
10.4%
|
77
9.5%
|
88
10.6%
|
252
10.2%
|
| Chile |
2
0.2%
|
1
0.1%
|
2
0.2%
|
5
0.2%
|
| Russian Federation |
45
5.4%
|
49
6%
|
46
5.5%
|
140
5.6%
|
| Israel |
34
4%
|
34
4.2%
|
34
4.1%
|
102
4.1%
|
| Italy |
67
8%
|
65
8%
|
61
7.4%
|
193
7.8%
|
| India |
24
2.9%
|
23
2.8%
|
24
2.9%
|
71
2.9%
|
| France |
60
7.1%
|
55
6.8%
|
50
6%
|
165
6.6%
|
| Australia |
30
3.6%
|
28
3.4%
|
31
3.7%
|
89
3.6%
|
| Denmark |
47
5.6%
|
58
7.1%
|
42
5.1%
|
147
5.9%
|
| South Africa |
34
4%
|
42
5.2%
|
30
3.6%
|
106
4.3%
|
| Korea, Republic of |
4
0.5%
|
3
0.4%
|
2
0.2%
|
9
0.4%
|
| Austria |
12
1.4%
|
8
1%
|
11
1.3%
|
31
1.2%
|
| United Kingdom |
33
3.9%
|
29
3.6%
|
30
3.6%
|
92
3.7%
|
| Czech Republic |
43
5.1%
|
49
6%
|
48
5.8%
|
140
5.6%
|
| Mexico |
22
2.6%
|
18
2.2%
|
22
2.7%
|
62
2.5%
|
| Canada |
22
2.6%
|
17
2.1%
|
15
1.8%
|
54
2.2%
|
| Argentina |
7
0.8%
|
9
1.1%
|
6
0.7%
|
22
0.9%
|
| Poland |
45
5.4%
|
44
5.4%
|
48
5.8%
|
137
5.5%
|
| Brazil |
19
2.3%
|
24
3%
|
30
3.6%
|
73
2.9%
|
| Singapore |
1
0.1%
|
2
0.2%
|
3
0.4%
|
6
0.2%
|
| Romania |
6
0.7%
|
7
0.9%
|
7
0.8%
|
20
0.8%
|
| Norway |
9
1.1%
|
9
1.1%
|
10
1.2%
|
28
1.1%
|
| Germany |
62
7.4%
|
55
6.8%
|
60
7.2%
|
177
7.1%
|
| Index Event Classification (participants) [Number] | ||||
| Proximal DVT |
544
64.8%
|
527
64.8%
|
551
66.5%
|
1622
65.4%
|
| PE |
296
35.2%
|
286
35.2%
|
278
33.5%
|
860
34.6%
|
Outcome Measures
| Title | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=32, 34, 96 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively; number of events imputed=13, 20, 19, respectively. Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0381
0%
|
0.0418
0%
|
0.1158
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.3283 | |
| Confidence Interval |
(2-Sided) 95% 0.2225 to 0.4844 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.3615 | |
| Confidence Interval |
(2-Sided) 95% 0.2475 to 0.5281 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=27, 34, 92 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. Number of imputed events=13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0321
0%
|
0.0418
0%
|
0.1110
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.2891 | |
| Confidence Interval |
(2-Sided) 95% 0.1902 to 0.4395 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.3774 | |
| Confidence Interval |
(2-Sided) 95% 0.2577 to 0.5525 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned.(n)number of events = 19, 14, 77 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. All events were counted; no events were imputed. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0226
0%
|
0.0172
0%
|
0.0929
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.2422 | |
| Confidence Interval |
(2-Sided) 95% 0.1476 to 0.3975 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.1861 | |
| Confidence Interval |
(2-Sided) 95% 0.1062 to 0.3261 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with consent.(n)number of events=27, 34, 95 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. The (n)number of imputed events were = 13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [proportion of participants] |
0.0321
0%
|
0.0418
0%
|
0.1146
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.2799 | |
| Confidence Interval |
(2-Sided) 95% 0.1844 to 0.4247 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.3653 | |
| Confidence Interval |
(2-Sided) 95% 0.2500 to 0.5338 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 19, 28, 72 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0226
0%
|
0.0344
0%
|
0.0869
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.2615 | |
| Confidence Interval |
(2-Sided) 95% 0.1593 to 0.4292 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.3972 | |
| Confidence Interval |
(2-Sided) 95% 0.2595 to 0.6079 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 23, 25, 37 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0274
0%
|
0.0308
0%
|
0.0446
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1084 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.6087 | |
| Confidence Interval |
(2-Sided) 95% 0.3653 to 1.0145 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1329 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.6846 | |
| Confidence Interval |
(2-Sided) 95% 0.4164 to 1.1257 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 17, 24, 26 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0202
0%
|
0.0295
0%
|
0.0314
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3059 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.6470 | |
| Confidence Interval |
(2-Sided) 95% 0.3543 to 1.1813 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8288 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.9416 | |
| Confidence Interval |
(2-Sided) 95% 0.5458 to 1.6245 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. number of events (n)= 17, 24, 29 in the apixaban 2.5 mg, 5 mg, placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of Participants] |
0.0202
0%
|
0.0295
0%
|
0.0350
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1316 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.5794 | |
| Confidence Interval |
(2-Sided) 95% 0.3215 to 1.0443 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5288 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.8433 | |
| Confidence Interval |
(2-Sided) 95% 0.4959 to 1.4341 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation |
|---|---|
| Description | DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. (n) number of events = 22, 25, 33 in apixaban 2.5 mg, apixaban 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0262
0%
|
0.0308
0%
|
0.0398
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2361 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.6577 | |
| Confidence Interval |
(2-Sided) 95% 0.3874 to 1.1169 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3155 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.7708 | |
| Confidence Interval |
(2-Sided) 95% 0.4631 to 1.2832 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation |
|---|---|
| Description | All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. In first event (first primary event) each participant counted once. In event category, each participant was counted only once in each event category but could have been counted in multiple categories. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| First event: Participants with nonfatal DVT |
6
0.7%
|
7
0.9%
|
53
6.4%
|
| First event: Participants with nonfatal PE |
7
0.8%
|
4
0.5%
|
13
1.6%
|
| First event: All-Cause Death |
6
0.7%
|
3
0.4%
|
11
1.3%
|
| CV-related Death (included in all-cause total) |
0
0%
|
0
0%
|
3
0.4%
|
| VTE-related Death (included in all-cause total) |
2
0.2%
|
3
0.4%
|
7
0.8%
|
| Participants with event: nonfatal DVT |
6
0.7%
|
8
1%
|
53
6.4%
|
| Participants with event: nonfatal PE |
8
1%
|
4
0.5%
|
15
1.8%
|
| Participants with event: All cause death |
7
0.8%
|
4
0.5%
|
14
1.7%
|
| Title | Adjudicated Major Bleeding During the Treatment Period - Treated Population |
|---|---|
| Description | Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 2, 1, 4 in apixaban 2.5 mg, and 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 811 | 826 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0024
0%
|
0.0012
0%
|
0.0048
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Treated participants with at least one dose of study drug were included. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3925 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.4850 | |
| Confidence Interval |
(2-Sided) 95% 0.0891 to 2.6391 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Participants treated with at least one dose of study drug were included. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3551 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.2457 | |
| Confidence Interval |
(2-Sided) 95% 0.0269 to 2.2437 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants |
|---|---|
| Description | Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated participants were those who received at least 1 dose of study drug. (n)number of events = 27, 35, 22 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 811 | 826 |
| Number (95% Confidence Interval) [proportion of participants] |
0.0321
0%
|
0.0432
0%
|
0.0266
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5148 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.2027 | |
| Confidence Interval |
(2-Sided) 95% 0.6897 to 2.0975 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1412 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.6160 | |
| Confidence Interval |
(2-Sided) 95% 0.9554 to 2.7336 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants |
|---|---|
| Description | Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Time Frame | Day 1 up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 25, 34, 19 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 811 | 826 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0298
0%
|
0.0419
0%
|
0.0230
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3932 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.2928 | |
| Confidence Interval |
(2-Sided) 95% 0.7158 to 2.3348 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0621 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.8235 | |
| Confidence Interval |
() 95% 1.0470 to 3.1760 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants |
|---|---|
| Description | All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Time Frame | Day 1 up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 75, 98, 58 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 811 | 826 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0893
0%
|
0.1208
0%
|
0.0702
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1691 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.2579 | |
| Confidence Interval |
(2-Sided) 95% 0.9064 to 1.7457 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.6971 | |
| Confidence Interval |
(2-Sided) 95% 1.2468 to 2.3102 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Total Bleeding During the Treatment Period - Treated Participants |
|---|---|
| Description | All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Time Frame | Day 1 up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 94, 121, 74 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 811 | 826 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.1119
0%
|
0.1492
0%
|
0.0896
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 2.5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1466 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.2374 | |
| Confidence Interval |
(2-Sided) 95% 0.9276 to 1.6507 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Apixaban 5 mg, Placebo |
|---|---|---|
| Comments | Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding is any major, clinically relevant non-major, or minor bleeding. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | Hochberg adjusted p-value for superiority based on 2 hypotheses tests for apixaban 2.5mg group comparing with placebo group and for apixaban 5mg group comparing with placebo group. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.6468 | |
| Confidence Interval |
(2-Sided) 95% 1.2552 to 2.1606 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 73 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [proportion of participants] |
0.0167
0%
|
0.0172
0%
|
0.0881
0%
|
| Title | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 76 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [proportion of participants] |
0.0167
0%
|
0.0172
0%
|
0.0917
0%
|
| Title | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 6, 8, 53 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [proportion of participants] |
0.0071
0%
|
0.0098
0%
|
0.0639
0%
|
| Title | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 8, 4, 15 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0095
0%
|
0.0049
0%
|
0.0181
0%
|
| Title | Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 7 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0024
0%
|
0.0037
0%
|
0.0084
0%
|
| Title | Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 10 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0024
0%
|
0.0037
0%
|
0.0121
0%
|
| Title | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation |
|---|---|
| Description | DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Time Frame | Day 1 up to 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 7, 4, 14 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Arm/Group Title | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID. | Participants received 5 mg oral tablet apixaban BID. | Participants received matching placebo oral tablet BID. |
| Measure Participants | 840 | 813 | 829 |
| Number (95% Confidence Interval) [Proportion of participants] |
0.0083
0%
|
0.0049
0%
|
0.0169
0%
|
Adverse Events
| Time Frame | Day 1 up to 12 months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Apixaban 2.5mg | Apixaban 5mg | Placebo | |||
| Arm/Group Description | Participants received 2.5 mg oral tablet apixaban BID | Participants received 5 mg oral tablet apixaban BID | Participants received oral tablet of placebo BID | |||
All Cause Mortality |
||||||
| Apixaban 2.5mg | Apixaban 5mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Apixaban 2.5mg | Apixaban 5mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 112/840 (13.3%) | 107/811 (13.2%) | 158/826 (19.1%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 0/840 (0%) | 3/811 (0.4%) | 2/826 (0.2%) | |||
| IRON DEFICIENCY ANAEMIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| Cardiac disorders | ||||||
| ACUTE CORONARY SYNDROME | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ACUTE MYOCARDIAL INFARCTION | 1/840 (0.1%) | 2/811 (0.2%) | 0/826 (0%) | |||
| ANGINA PECTORIS | 3/840 (0.4%) | 0/811 (0%) | 0/826 (0%) | |||
| ANGINA UNSTABLE | 1/840 (0.1%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| ARTERIOSCLEROSIS CORONARY ARTERY | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ATRIAL FIBRILLATION | 2/840 (0.2%) | 1/811 (0.1%) | 4/826 (0.5%) | |||
| BRADYCARDIA | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| CARDIAC ARREST | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CARDIAC FAILURE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CARDIAC FAILURE CONGESTIVE | 2/840 (0.2%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CARDIO-RESPIRATORY ARREST | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| CONGESTIVE CARDIOMYOPATHY | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CORONARY ARTERY DISEASE | 2/840 (0.2%) | 0/811 (0%) | 1/826 (0.1%) | |||
| EXTRASYSTOLES | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| MITRAL VALVE INCOMPETENCE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| MYOCARDIAL INFARCTION | 1/840 (0.1%) | 3/811 (0.4%) | 2/826 (0.2%) | |||
| MYOCARDIAL ISCHAEMIA | 0/840 (0%) | 1/811 (0.1%) | 3/826 (0.4%) | |||
| SICK SINUS SYNDROME | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| TACHYCARDIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| VENTRICULAR FIBRILLATION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| Congenital, familial and genetic disorders | ||||||
| HIP DYSPLASIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Ear and labyrinth disorders | ||||||
| OTOSCLEROSIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| VERTIGO | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| Endocrine disorders | ||||||
| THYROIDITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| Eye disorders | ||||||
| CATARACT | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| EYE HAEMORRHAGE | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| MACULAR OEDEMA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| RETINAL HAEMORRHAGE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| RETINAL VEIN OCCLUSION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| RETINAL VEIN THROMBOSIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ABDOMINAL PAIN LOWER | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ABDOMINAL STRANGULATED HERNIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ANAL FISSURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTRIC ULCER HAEMORRHAGE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTRITIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTROINTESTINAL HAEMORRHAGE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| GASTROOESOPHAGEAL REFLUX DISEASE | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| HAEMATEMESIS | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| HAEMORRHOIDAL HAEMORRHAGE | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| HIATUS HERNIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ILEUS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| INGUINAL HERNIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| INTESTINAL ISCHAEMIA | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PANCREATITIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| PANCREATITIS ACUTE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| POLYP COLORECTAL | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| RECTAL HAEMORRHAGE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SMALL INTESTINAL OBSTRUCTION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| VOMITING | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| General disorders | ||||||
| ASTHENIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| CHEST PAIN | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| DEATH | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| FATIGUE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| MULTI-ORGAN FAILURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| NON-CARDIAC CHEST PAIN | 1/840 (0.1%) | 0/811 (0%) | 2/826 (0.2%) | |||
| OEDEMA PERIPHERAL | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PYREXIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SUDDEN DEATH | 0/840 (0%) | 1/811 (0.1%) | 3/826 (0.4%) | |||
| Hepatobiliary disorders | ||||||
| BILE DUCT STONE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CHOLANGITIS ACUTE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| CHOLECYSTITIS | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| CHOLECYSTITIS ACUTE | 3/840 (0.4%) | 0/811 (0%) | 0/826 (0%) | |||
| CHOLECYSTITIS CHRONIC | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| CHOLELITHIASIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| DRUG-INDUCED LIVER INJURY | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| HEPATITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| Immune system disorders | ||||||
| AMYLOIDOSIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ANTIPHOSPHOLIPID SYNDROME | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| Infections and infestations | ||||||
| ACUTE SINUSITIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| BRONCHITIS | 1/840 (0.1%) | 2/811 (0.2%) | 1/826 (0.1%) | |||
| BRONCHOPNEUMONIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| CELLULITIS | 2/840 (0.2%) | 0/811 (0%) | 2/826 (0.2%) | |||
| DIVERTICULITIS | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| EMPYEMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ENCEPHALITIS MENINGOCOCCAL | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ERYSIPELAS | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ESCHERICHIA SEPSIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTROENTERITIS | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| HAEMATOMA INFECTION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| HERPES ZOSTER | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| LOBAR PNEUMONIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LOWER RESPIRATORY TRACT INFECTION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ORCHITIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| OSTEOMYELITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PERIRECTAL ABSCESS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| PNEUMONIA | 5/840 (0.6%) | 3/811 (0.4%) | 1/826 (0.1%) | |||
| PYELONEPHRITIS | 0/840 (0%) | 2/811 (0.2%) | 1/826 (0.1%) | |||
| RESPIRATORY TRACT INFECTION | 0/840 (0%) | 3/811 (0.4%) | 1/826 (0.1%) | |||
| SALPINGITIS | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| SEPSIS | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| SINUSITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| TONSILLITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| URINARY TRACT INFECTION | 1/840 (0.1%) | 2/811 (0.2%) | 1/826 (0.1%) | |||
| VIRAL INFECTION | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| VIRAL SINUSITIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| ACCIDENTAL EXPOSURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ANKLE FRACTURE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CONCUSSION | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| FEMUR FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| FOREIGN BODY | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| FRACTURED SACRUM | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| HAND FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| HEAT EXHAUSTION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| HIP FRACTURE | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| HUMERUS FRACTURE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| INCISIONAL HERNIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| JOINT INJURY | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LACERATION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LIGAMENT RUPTURE | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| LIMB INJURY | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| LOWER LIMB FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LUMBAR VERTEBRAL FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| MENISCUS LESION | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| OVERDOSE | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| POST PROCEDURAL HAEMATOMA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| POST PROCEDURAL HAEMORRHAGE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| RADIUS FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SPINAL COMPRESSION FRACTURE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SPINAL FRACTURE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| THERMAL BURN | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| TOXICITY TO VARIOUS AGENTS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| WOUND HAEMORRHAGE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| WRIST FRACTURE | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| Investigations | ||||||
| BIOPSY BONE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| COAGULATION TIME PROLONGED | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| PLATELET COUNT DECREASED | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| DEHYDRATION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| DIABETES MELLITUS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ELECTROLYTE IMBALANCE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| HYPERGLYCAEMIA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| HYPONATRAEMIA | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHRALGIA | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| ARTHRITIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| INTERVERTEBRAL DISC DEGENERATION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| INTERVERTEBRAL DISC PROTRUSION | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| JOINT ANKYLOSIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LIGAMENT DISORDER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LUMBAR SPINAL STENOSIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| MUSCULOSKELETAL CHEST PAIN | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| MUSCULOSKELETAL PAIN | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| OSTEOARTHRITIS | 3/840 (0.4%) | 0/811 (0%) | 3/826 (0.4%) | |||
| PSORIATIC ARTHROPATHY | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| RHEUMATOID ARTHRITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ROTATOR CUFF SYNDROME | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SCOLIOSIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| TENDONITIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| BASAL CELL CARCINOMA | 2/840 (0.2%) | 0/811 (0%) | 1/826 (0.1%) | |||
| BENIGN PANCREATIC NEOPLASM | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| BREAST CANCER | 1/840 (0.1%) | 2/811 (0.2%) | 3/826 (0.4%) | |||
| CARCINOID TUMOUR | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| CERVIX CARCINOMA | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| COLON ADENOMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| COLON CANCER | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| COLON CANCER METASTATIC | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ENDOMETRIAL CANCER | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTROINTESTINAL CARCINOMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| GASTROINTESTINAL STROMAL TUMOUR | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| LIP AND/OR ORAL CAVITY CANCER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LIPOMA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| LUNG ADENOCARCINOMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| LUNG NEOPLASM MALIGNANT | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| MALIGNANT MELANOMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| METASTASES TO BONE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| METASTATIC BRONCHIAL CARCINOMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| METASTATIC NEOPLASM | 3/840 (0.4%) | 0/811 (0%) | 0/826 (0%) | |||
| MULTIPLE MYELOMA | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| MYELODYSPLASTIC SYNDROME | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| NON-HODGKIN'S LYMPHOMA RECURRENT | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| OVARIAN ADENOMA | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| OVARIAN NEOPLASM | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PANCREATIC NEOPLASM | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PROSTATE CANCER | 2/840 (0.2%) | 1/811 (0.1%) | 0/826 (0%) | |||
| RECTAL CANCER RECURRENT | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| RENAL CANCER | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| SKIN CANCER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SQUAMOUS CELL CARCINOMA OF SKIN | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| THYROID CANCER | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| UTERINE LEIOMYOMA | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| VOCAL CORD NEOPLASM | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Nervous system disorders | ||||||
| CEREBRAL HAEMORRHAGE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| CEREBROVASCULAR ACCIDENT | 1/840 (0.1%) | 1/811 (0.1%) | 3/826 (0.4%) | |||
| CONVULSION | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| DEMYELINATING POLYNEUROPATHY | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| EPILEPSY | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| EXTRAPYRAMIDAL DISORDER | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| FEBRILE CONVULSION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| HEADACHE | 0/840 (0%) | 2/811 (0.2%) | 0/826 (0%) | |||
| HEMIANOPIA HOMONYMOUS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ISCHAEMIC STROKE | 1/840 (0.1%) | 1/811 (0.1%) | 2/826 (0.2%) | |||
| MIGRAINE | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| MULTIPLE SCLEROSIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| OPTIC NEURITIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| PRESYNCOPE | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SCIATICA | 2/840 (0.2%) | 0/811 (0%) | 0/826 (0%) | |||
| SYNCOPE | 1/840 (0.1%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| TRANSIENT ISCHAEMIC ATTACK | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| ABORTION SPONTANEOUS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| PREGNANCY | 3/840 (0.4%) | 4/811 (0.5%) | 1/826 (0.1%) | |||
| Psychiatric disorders | ||||||
| ALCOHOLISM | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| DELIRIUM | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| DEPRESSION | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| DRUG DEPENDENCE | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PANIC ATTACK | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| SUICIDAL IDEATION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Renal and urinary disorders | ||||||
| CALCULUS URINARY | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| HAEMATURIA | 0/840 (0%) | 2/811 (0.2%) | 2/826 (0.2%) | |||
| HYDRONEPHROSIS | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| NEPHROLITHIASIS | 2/840 (0.2%) | 0/811 (0%) | 1/826 (0.1%) | |||
| RENAL COLIC | 0/840 (0%) | 1/811 (0.1%) | 3/826 (0.4%) | |||
| RENAL FAILURE ACUTE | 2/840 (0.2%) | 0/811 (0%) | 2/826 (0.2%) | |||
| RENAL IMPAIRMENT | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| URETERIC STENOSIS | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| URINARY RETENTION | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| Reproductive system and breast disorders | ||||||
| METRORRHAGIA | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| OVARIAN CYST | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| ACUTE PULMONARY OEDEMA | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| ALLERGIC GRANULOMATOUS ANGIITIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ASTHMA | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| ASTHMATIC CRISIS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| BRONCHITIS CHRONIC | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 3/840 (0.4%) | 3/811 (0.4%) | 2/826 (0.2%) | |||
| DYSPNOEA EXERTIONAL | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| EPISTAXIS | 0/840 (0%) | 2/811 (0.2%) | 1/826 (0.1%) | |||
| HAEMOPTYSIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| LARYNGEAL OEDEMA | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PLEURAL EFFUSION | 0/840 (0%) | 0/811 (0%) | 2/826 (0.2%) | |||
| PLEURISY | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PLEURITIC PAIN | 1/840 (0.1%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PULMONARY EMBOLISM | 5/840 (0.6%) | 3/811 (0.4%) | 20/826 (2.4%) | |||
| RESPIRATORY DISORDER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| SLEEP APNOEA SYNDROME | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| DECUBITUS ULCER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| DIABETIC FOOT | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| Social circumstances | ||||||
| MISCARRIAGE OF PARTNER | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| PREGNANCY OF PARTNER | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| Surgical and medical procedures | ||||||
| ABORTION INDUCED | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| HOSPITALISATION | 0/840 (0%) | 2/811 (0.2%) | 1/826 (0.1%) | |||
| Vascular disorders | ||||||
| ANEURYSM | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| ARTERIAL DISORDER | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| DEEP VEIN THROMBOSIS | 3/840 (0.4%) | 9/811 (1.1%) | 40/826 (4.8%) | |||
| EMBOLISM VENOUS | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| FEMORAL ARTERY EMBOLISM | 1/840 (0.1%) | 1/811 (0.1%) | 0/826 (0%) | |||
| HAEMATOMA | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| HYPERTENSIVE CRISIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| HYPOTENSION | 0/840 (0%) | 1/811 (0.1%) | 1/826 (0.1%) | |||
| MALIGNANT HYPERTENSION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| ORTHOSTATIC HYPOTENSION | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| PERIPHERAL VASCULAR DISORDER | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| THROMBOPHLEBITIS SUPERFICIAL | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| THROMBOSIS | 1/840 (0.1%) | 0/811 (0%) | 0/826 (0%) | |||
| VARICOPHLEBITIS | 0/840 (0%) | 1/811 (0.1%) | 0/826 (0%) | |||
| VENOUS INSUFFICIENCY | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
| VENOUS THROMBOSIS | 0/840 (0%) | 0/811 (0%) | 3/826 (0.4%) | |||
| VENOUS THROMBOSIS LIMB | 0/840 (0%) | 0/811 (0%) | 1/826 (0.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Apixaban 2.5mg | Apixaban 5mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 341/840 (40.6%) | 305/811 (37.6%) | 318/826 (38.5%) | |||
| Gastrointestinal disorders | ||||||
| CONSTIPATION | 18/840 (2.1%) | 12/811 (1.5%) | 14/826 (1.7%) | |||
| DIARRHOEA | 37/840 (4.4%) | 24/811 (3%) | 24/826 (2.9%) | |||
| NAUSEA | 20/840 (2.4%) | 18/811 (2.2%) | 20/826 (2.4%) | |||
| General disorders | ||||||
| FATIGUE | 17/840 (2%) | 14/811 (1.7%) | 10/826 (1.2%) | |||
| OEDEMA PERIPHERAL | 28/840 (3.3%) | 25/811 (3.1%) | 33/826 (4%) | |||
| Infections and infestations | ||||||
| BRONCHITIS | 24/840 (2.9%) | 30/811 (3.7%) | 13/826 (1.6%) | |||
| INFLUENZA | 18/840 (2.1%) | 20/811 (2.5%) | 20/826 (2.4%) | |||
| NASOPHARYNGITIS | 41/840 (4.9%) | 31/811 (3.8%) | 40/826 (4.8%) | |||
| UPPER RESPIRATORY TRACT INFECTION | 18/840 (2.1%) | 18/811 (2.2%) | 18/826 (2.2%) | |||
| URINARY TRACT INFECTION | 28/840 (3.3%) | 30/811 (3.7%) | 34/826 (4.1%) | |||
| Investigations | ||||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 26/840 (3.1%) | 20/811 (2.5%) | 21/826 (2.5%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHRALGIA | 32/840 (3.8%) | 21/811 (2.6%) | 22/826 (2.7%) | |||
| BACK PAIN | 27/840 (3.2%) | 45/811 (5.5%) | 24/826 (2.9%) | |||
| MUSCLE SPASMS | 21/840 (2.5%) | 16/811 (2%) | 13/826 (1.6%) | |||
| PAIN IN EXTREMITY | 44/840 (5.2%) | 52/811 (6.4%) | 54/826 (6.5%) | |||
| Nervous system disorders | ||||||
| DIZZINESS | 20/840 (2.4%) | 18/811 (2.2%) | 15/826 (1.8%) | |||
| HEADACHE | 44/840 (5.2%) | 41/811 (5.1%) | 42/826 (5.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| COUGH | 21/840 (2.5%) | 21/811 (2.6%) | 18/826 (2.2%) | |||
| DYSPNOEA | 18/840 (2.1%) | 15/811 (1.8%) | 19/826 (2.3%) | |||
| EPISTAXIS | 13/840 (1.5%) | 27/811 (3.3%) | 8/826 (1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| RASH | 18/840 (2.1%) | 8/811 (1%) | 12/826 (1.5%) | |||
| Vascular disorders | ||||||
| DEEP VEIN THROMBOSIS | 12/840 (1.4%) | 8/811 (1%) | 23/826 (2.8%) | |||
| HYPERTENSION | 34/840 (4%) | 19/811 (2.3%) | 14/826 (1.7%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00633893
Other Study ID Numbers:
- CV185-057
- EUDRACT: 2007-004953-27
First Posted:
Mar 12, 2008
Last Update Posted:
Nov 25, 2013
Last Verified:
Oct 1, 2013