Once - Daily Oral Direct Factor Xa Inhibitor Rivaroxaban In The Long-Term Prevention Of Recurrent Symptomatic Venous Thromboembolism In Patients With Symptomatic Deep-Vein Thrombosis Or Pulmonary Embolism. The Einstein-Extension Study
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT00439725
Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
1,197
322
2
31
3.7
0.1
Study Details
Study Description
Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled, event-driven, superiority study for efficacy. Patients with confirmed symptomatic DVT (deep vein thrombosis) or PE (pulmonary embolism) who completed 6 or 12 months of treatment with rivaroxaban or VKA (vitamin K antagonist) are eligible for this trial (Einstein-Extension study).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.
The treatment period was followed by an observational period of 30 days starting the day after the last intake of study medication, regardless of the actual duration of study drug administration. Participants who did not complete the treatment period also entered the observational period. It was also possible that participants did not enter the observational period, e.g. due to withdrawal of consent or termination of study participation.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1197 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Once-daily Oral Direct Factor Xa Inhibitor Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism. The Einstein-Extension Study
Study Start Date
:
Feb 1, 2007
Actual Primary Completion Date
:
Aug 1, 2009
Actual Study Completion Date
:
Sep 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rivaroxaban (Xarelto, BAY59-7939) Participants were to receive rivaroxaban 20 mg oral tablet once daily |
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Patients randomized to rivaroxaban will receive rivaroxaban 20 mg once-daily.
|
| Placebo Comparator: Placebo Participants were to receive matching placebo oral tablet once daily |
Drug: Placebo
Patients allocated to placebo will receive a matching placebo tablet once daily.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries. For definition of DVT/PE, kindly refer to the link in the Protocol section.
Secondary Outcome Measures
- Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), or lung scintigraphy (for PE), and/or case summaries.
- Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
- Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Major Bleeding [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee (CIAC) blinded to treatment. Major bleeding event was overt bleeding associated with a 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Treatment-emergent [after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)] events and all events post randomization were reported.
- Percentage of Participants With Clinically Relevant Bleeding [6- or 12-month study treatment period]
All events adjudicated/confirmed by CIAC blinded to treatment. Clinically relevant bleeding included major bleeding (definition: see outcome 7) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of daily life activities. Treatment-emergent events (after intake of 1st study medication tablet as randomized up to 2 days after stop of study medication ['time window: 2 days']) and all events post randomization were reported
- Percentage of Participants With All Death [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries. Treatment-emergent events and all events post randomization were reported. Treatment-emergent: after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)
- Percentage of Participants With Other Vascular Events [6- or 12-month study treatment period]
All pre-defined vascular events (acute coronary syndromes, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism and vascular death) were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on results/films/images of confirmatory testing, and/or case summaries. On treatment events and all events post randomization were reported. On treatment: after intake of first tablet of study medication as randomized but not more than 1 day after stop of study medication (referred to as time window: 1 day)
Other Outcome Measures
- Percentage of Participants With Death (PE) Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment [6- or 12-month study treatment period]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Symptomatic Recurrent PE During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events During Observational Period [30 days observational period after last intake of study medication]
Events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral CT scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units, occurring in a critical site or contributing to death.
- Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries.
- Percentage of Participants With Recurrent DVT During Observational Period [30 days observational period after last intake of study medication]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound or venography, results/films/images of confirmatory testing, and/or case summaries.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Patients with confirmed symptomatic PE or DVT who have been treated for 6 or 12 months with VKA or rivaroxaban
Exclusion Criteria:
-
Legal lower age limitations (country specific)
-
Indication for VKA other than DVT and/or PE
-
Patients in whom anticoagulant treatment for their index PE or DVT should be continued
-
Childbearing potential without proper contraceptive measures, pregnancy or breast feeding. Proper contraceptive measures are defined as a method of contraception with a failure rate < 1 % during the course of the study (including the observational period). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP [Committee for Proprietary Medicinal Products]/ICH [International Conference on Harmonization]/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence and vasectomy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Little Rock | Arkansas | United States | 72205 | |
| 2 | Los Angeles | California | United States | 90095 | |
| 3 | Redlands | California | United States | 92373 | |
| 4 | Bay Pines | Florida | United States | 33744 | |
| 5 | Melbourne | Florida | United States | 32901 | |
| 6 | Miami | Florida | United States | 33136-1096 | |
| 7 | Miami | Florida | United States | 33136 | |
| 8 | Decatur | Georgia | United States | 30033 | |
| 9 | Idaho Falls | Idaho | United States | 83404 | |
| 10 | Covington | Louisiana | United States | 70433 | |
| 11 | Baltimore | Maryland | United States | 21215-5271 | |
| 12 | Boston | Massachusetts | United States | 02215 | |
| 13 | Albuquerque | New Mexico | United States | 87108 | |
| 14 | Chapel Hill | North Carolina | United States | 27599-7035 | |
| 15 | Greensboro | North Carolina | United States | 27401 | |
| 16 | Greensboro | North Carolina | United States | 27403 | |
| 17 | Oklahoma City | Oklahoma | United States | 73104 | |
| 18 | Pittsburgh | Pennsylvania | United States | 15224 | |
| 19 | Corsicana | Texas | United States | 75110 | |
| 20 | San Antonio | Texas | United States | 78229 | |
| 21 | Murray | Utah | United States | 84107 | |
| 22 | Salt Lake City | Utah | United States | 84132 | |
| 23 | Burlington | Vermont | United States | 05401 | |
| 24 | Fredericksburg | Virginia | United States | 22401 | |
| 25 | Spokane | Washington | United States | 99204 | |
| 26 | Garran | Australian Capital Territory | Australia | 2605 | |
| 27 | Gosford | New South Wales | Australia | 2250 | |
| 28 | Kogarah | New South Wales | Australia | 2217 | |
| 29 | Lismore | New South Wales | Australia | 2480 | |
| 30 | St Leonards | New South Wales | Australia | 2065 | |
| 31 | Sydney | New South Wales | Australia | 2010 | |
| 32 | Sydney | New South Wales | Australia | 2031 | |
| 33 | Sydney | New South Wales | Australia | 2139 | |
| 34 | Sydney | New South Wales | Australia | 2229 | |
| 35 | Brisbane | Queensland | Australia | 4029 | |
| 36 | Redcliffe | Queensland | Australia | 4020 | |
| 37 | Southport | Queensland | Australia | 4215 | |
| 38 | Woolloongabba | Queensland | Australia | 4102 | |
| 39 | Adelaide | South Australia | Australia | 5011 | |
| 40 | Adelaide | South Australia | Australia | 5042 | |
| 41 | Box Hill | Victoria | Australia | 3128 | |
| 42 | Clayton | Victoria | Australia | 3168 | |
| 43 | Geelong | Victoria | Australia | 3220 | |
| 44 | Melbourne | Victoria | Australia | 3135 | |
| 45 | Melbourne | Victoria | Australia | 3181 | |
| 46 | Prahran | Victoria | Australia | 3181 | |
| 47 | Fremantle | Western Australia | Australia | 6160 | |
| 48 | Perth | Western Australia | Australia | 6000 | |
| 49 | Graz | Steiermark | Austria | 8036 | |
| 50 | Innsbruck | Tirol | Austria | 6020 | |
| 51 | Feldkirch | Vorarlberg | Austria | 6807 | |
| 52 | Salzburg | Austria | 5020 | ||
| 53 | Wien | Austria | 1090 | ||
| 54 | Wien | Austria | 1140 | ||
| 55 | Bruxelles - Brussel | Belgium | 1070 | ||
| 56 | Bruxelles - Brussel | Belgium | 1200 | ||
| 57 | Duffel | Belgium | 2570 | ||
| 58 | Genk | Belgium | 3600 | ||
| 59 | Gent | Belgium | 9000 | ||
| 60 | Hasselt | Belgium | 3500 | ||
| 61 | Leuven | Belgium | 3000 | ||
| 62 | Liege | Belgium | 4000 | ||
| 63 | Lier | Belgium | 2500 | ||
| 64 | Namur | Belgium | 5000 | ||
| 65 | Sint-Truiden | Belgium | 3800 | ||
| 66 | Yvoir | Belgium | 5530 | ||
| 67 | Zottegem | Belgium | 9620 | ||
| 68 | Uberaba | Minas Gerais | Brazil | 38010 380 | |
| 69 | Curitiba | Parana | Brazil | 80050-350 | |
| 70 | Londrina | Parana | Brazil | 86038440 | |
| 71 | Porto Alegre | Rio Grande do Sul | Brazil | ||
| 72 | Botucatu | Sao Paulo | Brazil | 18618 000 | |
| 73 | Sorocaba | Sao Paulo | Brazil | 18031-000 | |
| 74 | São Paulo | Sao Paulo | Brazil | 01323-001 | |
| 75 | São Paulo | Sao Paulo | Brazil | 01509-900 | |
| 76 | São Paulo | Sao Paulo | Brazil | 04039-004 | |
| 77 | Rio de Janeiro | Brazil | |||
| 78 | Sao Paulo | Brazil | 04023-061 | ||
| 79 | Winnipeg | Manitoba | Canada | R2H 2A6 | |
| 80 | Toronto | Ontario | Canada | M6R 1B5 | |
| 81 | Guangzhou | Guangdong | China | 510080 | |
| 82 | Harbin | Heilongjiang | China | 150086 | |
| 83 | Wuhan | Hubei | China | 430022 | |
| 84 | Suzhou | Jiangsu | China | 215004 | |
| 85 | Shenyang | Liaoning | China | 110016 | |
| 86 | Beijing | China | 100020 | ||
| 87 | Beijing | China | 100029 | ||
| 88 | Beijing | China | 100037 | ||
| 89 | Beijing | China | 100038 | ||
| 90 | Beijing | China | 100044 | ||
| 91 | Beijing | China | 100730 | ||
| 92 | Beijing | China | 100853 | ||
| 93 | Shanghai | China | 200001 | ||
| 94 | Shanghai | China | 200032 | ||
| 95 | Shanghai | China | 200433 | ||
| 96 | Brno | Czech Republic | 65691 | ||
| 97 | Karlovy Vary | Czech Republic | 360 00 | ||
| 98 | Kladno | Czech Republic | 27259 | ||
| 99 | Ostrava-Poruba | Czech Republic | 708 52 | ||
| 100 | Ostrava | Czech Republic | 728 80 | ||
| 101 | Prague 5 | Czech Republic | 150 00 | ||
| 102 | Praha 1 | Czech Republic | 110 00 | ||
| 103 | Praha 2 | Czech Republic | 12800 | ||
| 104 | Praha 4 | Czech Republic | 140 21 | ||
| 105 | Usti nad Lebem | Czech Republic | 401 13 | ||
| 106 | Aarhus C | Denmark | 8000 | ||
| 107 | Braedstrup | Denmark | 8740 | ||
| 108 | Frederiksberg | Denmark | 2000F | ||
| 109 | Hellerup | Denmark | 2900 | ||
| 110 | Seinäjoki | Finland | 60220 | ||
| 111 | Agen Cedex 9 | France | 47923 | ||
| 112 | Amiens | France | 80000 | ||
| 113 | Angers Cedex 01 | France | 49033 | ||
| 114 | Arras | France | 62000 | ||
| 115 | Bordeaux | France | 33075 | ||
| 116 | Brest Cedex | France | 29609 | ||
| 117 | Castelnau Le Lez | France | 34170 | ||
| 118 | Clamart | France | 92141 | ||
| 119 | Clermont Ferrand | France | 63000 | ||
| 120 | Colombes | France | 92700 | ||
| 121 | Creteil | France | 94000 | ||
| 122 | Dijon | France | 21000 | ||
| 123 | Grenoble | France | 38028 | ||
| 124 | Grenoble | France | 38043 | ||
| 125 | Lille Cedex | France | 59037 | ||
| 126 | Limoges | France | 87042 | ||
| 127 | Montpellier Cedex | France | 34295 | ||
| 128 | Nantes | France | 44000 | ||
| 129 | Nimes Cedex 9 | France | 30029 | ||
| 130 | Orthez | France | 64300 | ||
| 131 | Paris Cedex 15 | France | 75908 | ||
| 132 | Paris | France | 75004 | ||
| 133 | Paris | France | 75475 | ||
| 134 | Paris | France | 75877 | ||
| 135 | Pierre Benite | France | 69495 | ||
| 136 | Roanne | France | 42328 | ||
| 137 | Rouen Cedex | France | 76031 | ||
| 138 | Saint Etienne | France | 42055 | ||
| 139 | Strasbourg Cedex | France | 67091 | ||
| 140 | Toulon | France | 83000 | ||
| 141 | Toulouse | France | 31403 | ||
| 142 | Tours | France | 37044 | ||
| 143 | Valenciennes Cedex | France | 59322 | ||
| 144 | Vandoeuvre Les Nancy | France | 54511 | ||
| 145 | Vernon | France | 27200 | ||
| 146 | Bruchsal | Baden-Württemberg | Germany | 76646 | |
| 147 | Heidelberg | Baden-Württemberg | Germany | 69115 | |
| 148 | Karlsbad | Baden-Württemberg | Germany | 76307 | |
| 149 | Mannheim | Baden-Württemberg | Germany | 68167 | |
| 150 | Neckargemünd | Baden-Württemberg | Germany | 69151 | |
| 151 | Tübingen | Baden-Württemberg | Germany | 72076 | |
| 152 | Augsburg | Bayern | Germany | 86156 | |
| 153 | München | Bayern | Germany | 80331 | |
| 154 | München | Bayern | Germany | 81377 | |
| 155 | Würzburg | Bayern | Germany | 97080 | |
| 156 | Darmstadt | Hessen | Germany | 64297 | |
| 157 | Frankfurt | Hessen | Germany | 60596 | |
| 158 | Gießen | Hessen | Germany | 35392 | |
| 159 | Wiesbaden | Hessen | Germany | 65183 | |
| 160 | Greifswald | Mecklenburg-Vorpommern | Germany | 17475 | |
| 161 | Hannover | Niedersachsen | Germany | 30625 | |
| 162 | Rotenburg | Niedersachsen | Germany | 27342 | |
| 163 | Düsseldorf | Nordrhein-Westfalen | Germany | 40225 | |
| 164 | Essen | Nordrhein-Westfalen | Germany | 45122 | |
| 165 | Paderborn | Nordrhein-Westfalen | Germany | 33098 | |
| 166 | Soest | Nordrhein-Westfalen | Germany | 59494 | |
| 167 | Witten | Nordrhein-Westfalen | Germany | 58455 | |
| 168 | Mainz | Rheinland-Pfalz | Germany | 55131 | |
| 169 | Homburg | Saarland | Germany | 66421 | |
| 170 | Homburg | Saarland | Germany | 66424 | |
| 171 | Halle | Sachsen-Anhalt | Germany | 06120 | |
| 172 | Magdeburg | Sachsen-Anhalt | Germany | 39112 | |
| 173 | Dresden | Sachsen | Germany | 01307 | |
| 174 | Leipzig | Sachsen | Germany | 04289 | |
| 175 | Berlin | Germany | 10713 | ||
| 176 | Berlin | Germany | 12099 | ||
| 177 | Hamburg | Germany | 20251 | ||
| 178 | Hong Kong | Hong Kong | |||
| 179 | Budapest | Hungary | 1096 | ||
| 180 | Budapest | Hungary | 1115 | ||
| 181 | Debrecen | Hungary | 4032 | ||
| 182 | Kecskemet | Hungary | 6000 | ||
| 183 | Kistarcsa | Hungary | 2143 | ||
| 184 | Miskolc | Hungary | 3526 | ||
| 185 | Nyiregyhaza | Hungary | 4400 | ||
| 186 | Szentes | Hungary | 6600 | ||
| 187 | Szombathely | Hungary | 9700 | ||
| 188 | Kochi | Kerala | India | 682026 | |
| 189 | Vellore | Kerala | India | 632004 | |
| 190 | Mumbai | Maharashtra | India | 400008 | |
| 191 | Mumbai | Maharashtra | India | 400016 | |
| 192 | Mumbai | Maharashtra | India | 400022 | |
| 193 | Hyderabad | India | 500082 | ||
| 194 | Kolkata | India | 700029 | ||
| 195 | New Delhi | India | 110060 | ||
| 196 | Pune | India | 411001 | ||
| 197 | Bandung | Indonesia | 40161 | ||
| 198 | Jakarta | Indonesia | 10430 | ||
| 199 | Medan | Indonesia | 20152 | ||
| 200 | Semarang | Indonesia | 50241 | ||
| 201 | Afula | Israel | 18101 | ||
| 202 | Ashkelon | Israel | 78278 | ||
| 203 | Beer Sheva | Israel | 84101 | ||
| 204 | Haifa | Israel | 31048 | ||
| 205 | Haifa | Israel | 31096 | ||
| 206 | Haifa | Israel | 34362 | ||
| 207 | Holon | Israel | 58100 | ||
| 208 | Jerusalem | Israel | 91120 | ||
| 209 | Kfar Saba | Israel | 44281 | ||
| 210 | Petach Tikva | Israel | 49100 | ||
| 211 | Rehovot | Israel | 76100 | ||
| 212 | Safed | Israel | 13100 | ||
| 213 | Tel Aviv | Israel | 64239 | ||
| 214 | Bologna | Italy | 40138 | ||
| 215 | Chieti | Italy | 66013 | ||
| 216 | Milano | Italy | 20132 | ||
| 217 | Milano | Italy | 20142 | ||
| 218 | Napoli | Italy | 80131 | ||
| 219 | Padova | Italy | 35128 | ||
| 220 | Palermo | Italy | 90127 | ||
| 221 | Parma | Italy | 43100 | ||
| 222 | Pavia | Italy | 27100 | ||
| 223 | Piacenza | Italy | 29100 | ||
| 224 | Venezia | Italy | 30122 | ||
| 225 | Daegu | Daegu Gwang'yeogsi | Korea, Republic of | 700721 | |
| 226 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 110-744 | |
| 227 | Daegu | Korea, Republic of | 705-718 | ||
| 228 | Seoul | Korea, Republic of | 120-752 | ||
| 229 | Seoul | Korea, Republic of | 137-701 | ||
| 230 | Taegu | Korea, Republic of | 700-712 | ||
| 231 | Selangor | Malaysia | 68000 | ||
| 232 | Amsterdam | Netherlands | 1105 AZ | ||
| 233 | Arnhem | Netherlands | 6815 AD | ||
| 234 | Den Bosch | Netherlands | 5223 GZ | ||
| 235 | Dordrecht | Netherlands | 3318 AT | ||
| 236 | Enschede | Netherlands | 7511 JX | ||
| 237 | Groningen | Netherlands | 9713 GZ | ||
| 238 | Hoofddorp | Netherlands | 2134 TM | ||
| 239 | Maastricht | Netherlands | 6229 HX | ||
| 240 | Rotterdam | Netherlands | 3083 AN | ||
| 241 | Zwijndrecht | Netherlands | 3331 LZ | ||
| 242 | Zwolle | Netherlands | 8025 AB | ||
| 243 | Auckland | New Zealand | 0622 | ||
| 244 | Auckland | New Zealand | 1023 | ||
| 245 | Christchurch | New Zealand | 8011 | ||
| 246 | Palmerston North | New Zealand | 4414 | ||
| 247 | Wellington South | New Zealand | 6021 | ||
| 248 | Fredrikstad | Norway | 1603 | ||
| 249 | Oslo | Norway | 0407 | ||
| 250 | Oslo | Norway | 0514 | ||
| 251 | Rud | Norway | 1309 | ||
| 252 | Quezon City | Philippines | 0850 | ||
| 253 | Quezon City | Philippines | 1102 | ||
| 254 | Bialystok | Poland | 15-276 | ||
| 255 | Bydgoszcz | Poland | 85-168 | ||
| 256 | Gdansk | Poland | 80-952 | ||
| 257 | Katowice | Poland | 40-365 | ||
| 258 | Krakow | Poland | 31-066 | ||
| 259 | Lodz | Poland | 90-153 | ||
| 260 | Lublin | Poland | 20-081 | ||
| 261 | Poznan | Poland | 60-631 | ||
| 262 | Poznan | Poland | 61-848 | ||
| 263 | Torun | Poland | 87-100 | ||
| 264 | Warszawa | Poland | 01-138 | ||
| 265 | Warszawa | Poland | 02-097 | ||
| 266 | Warszawa | Poland | 04-479 | ||
| 267 | Wroclaw | Poland | 50-326 | ||
| 268 | Wroclaw | Poland | 51-124 | ||
| 269 | Singapore | Singapore | 169608 | ||
| 270 | Singapore | Singapore | 308433 | ||
| 271 | Cape Town | Cape | South Africa | 7500 | |
| 272 | Johannesburg | Gauteng | South Africa | 2132 | |
| 273 | Johannesburg | Gauteng | South Africa | 2157 | |
| 274 | Johannesburg | Gauteng | South Africa | 2191 | |
| 275 | Johannesburg | Gauteng | South Africa | 2193 | |
| 276 | Pretoria | Gauteng | South Africa | 0084 | |
| 277 | Pretoria | Gauteng | South Africa | 0157 | |
| 278 | Pretoria | Gauteng | South Africa | 0181 | |
| 279 | Roodepoort | Gauteng | South Africa | 1724 | |
| 280 | Cape Town | Western Cape | South Africa | 7460 | |
| 281 | Somerset West | Western Cape | South Africa | 7130 | |
| 282 | Worcester | Western Cape | South Africa | 6850 | |
| 283 | Terrassa | Barcelona | Spain | 08221 | |
| 284 | Alcorcón | Madrid | Spain | 28922 | |
| 285 | Fuenlabrada | Madrid | Spain | 28942 | |
| 286 | Xàtiva | Valencia | Spain | 46800 | |
| 287 | Barcelona | Spain | 08025 | ||
| 288 | Barcelona | Spain | 08036 | ||
| 289 | Girona | Spain | 17007 | ||
| 290 | Madrid | Spain | 28034 | ||
| 291 | Pamplona | Spain | 31008 | ||
| 292 | Borås | Sweden | 501 82 | ||
| 293 | Göteborg | Sweden | 413 45 | ||
| 294 | Göteborg | Sweden | 416 85 | ||
| 295 | Jönköping | Sweden | 551 85 | ||
| 296 | Sundsvall | Sweden | 851 86 | ||
| 297 | Västervik | Sweden | 593 81 | ||
| 298 | Bruderholz | Basel-Landschaft | Switzerland | 4101 | |
| 299 | Genéve 14 | Genève 14 | Switzerland | 1211 | |
| 300 | Chur | Graubünden | Switzerland | 7000 | |
| 301 | Brig | Valais | Switzerland | 3900 | |
| 302 | Lugano | Switzerland | 6903 | ||
| 303 | Luzern | Switzerland | 6000 | ||
| 304 | Zürich | Switzerland | 8091 | ||
| 305 | Kaohsiung | Taiwan | 80756 | ||
| 306 | Tainan | Taiwan | 704 | ||
| 307 | Taipei | Taiwan | 10002 | ||
| 308 | Taipei | Taiwan | 11217 | ||
| 309 | Taoyuan | Taiwan | 333 | ||
| 310 | Bangkok | Thailand | 10400 | ||
| 311 | Bangkok | Thailand | 10700 | ||
| 312 | Pathumwan, Bangkok | Thailand | 10330 | ||
| 313 | Plymouth | Devon | United Kingdom | PL6 8DH | |
| 314 | Chelmsford | Essex | United Kingdom | CM1 5ET | |
| 315 | Romford | Essex | United Kingdom | RM7 0AG | |
| 316 | Isleworth | London | United Kingdom | TW7 6AF | |
| 317 | Edinburgh | Lothian | United Kingdom | EH16 4SA | |
| 318 | Liverpool | Merseyside | United Kingdom | L7 8XP | |
| 319 | London | United Kingdom | SE1 7EH | ||
| 320 | London | United Kingdom | SE5 9RS | ||
| 321 | London | United Kingdom | W1T 4EU | ||
| 322 | London | United Kingdom |
Sponsors and Collaborators
- Bayer
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Click here to find the definition for Deep Vein Thrombosis [DVT].
- Click here to find the definition for Pulmonary Embolism [PE].
- Click here and search for information of Bayer products for Europe
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00439725
Other Study ID Numbers:
- 11899
- 2006-004494-96
First Posted:
Feb 26, 2007
Last Update Posted:
Nov 4, 2014
Last Verified:
Oct 1, 2014
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants with confirmed symptomatic deep vein thrombosis or pulmonary embolism, who either had been treated for 6 or 12 months with warfarin or acenocoumarol or rivaroxaban in study NCT00440193, or who had been treated for 6 to 14 months with warfarin or acenocoumarol outside study NCT00440193, were recruited at specialized study sites. |
|---|---|
| Pre-assignment Detail | Out of 1200 participants screened, 3 failed screening (2 due to withdrawal of consent and 1 due to a protocol violation), and 1197 participants were randomized (602 to rivaroxaban and 595 to placebo). |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Period Title: Treatment Period | ||
| STARTED | 602 | 595 |
| Participants Received Treatment | 598 | 590 |
| COMPLETED | 366 | 349 |
| NOT COMPLETED | 236 | 246 |
| Period Title: Treatment Period | ||
| STARTED | 577 | 560 |
| COMPLETED | 569 | 553 |
| NOT COMPLETED | 8 | 7 |
Baseline Characteristics
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily | Total of all reporting groups |
| Overall Participants | 602 | 594 | 1196 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.2
(15.6)
|
58.4
(16.0)
|
58.3
(15.8)
|
| Age, Customized (participants) [Number] | |||
| 18 - 40 years |
87
14.5%
|
94
15.8%
|
181
15.1%
|
| >40 - <65 years |
273
45.3%
|
280
47.1%
|
553
46.2%
|
| 65 - 75 years |
153
25.4%
|
121
20.4%
|
274
22.9%
|
| >75 years |
89
14.8%
|
99
16.7%
|
188
15.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
248
41.2%
|
255
42.9%
|
503
42.1%
|
| Male |
354
58.8%
|
339
57.1%
|
693
57.9%
|
Outcome Measures
| Title | Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries. For definition of DVT/PE, kindly refer to the link in the Protocol section. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
1.3
0.2%
|
7.1
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (confidence interval) (two-sided testing). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | 1st test in a hierarchy, a p-value of less than 0.05 would be considered significant. | |
| Method | Regression, Cox | |
| Comments | Stratified by intended treatment duration, adjusted for pre-treatment | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.185 | |
| Confidence Interval |
() 95% 0.087 to 0.393 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3858 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), or lung scintigraphy (for PE), and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
1.3
0.2%
|
7.2
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | 2nd test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the 1st test in hierarchy was significant. | |
| Method | Regression, Cox | |
| Comments | Stratified by intended treatment duration, adjusted for pre-treatment | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.180 | |
| Confidence Interval |
() 95% 0.085 to 0.383 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3850 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
1.5
0.2%
|
7.4
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | 3rd test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the previous tests in hierarchy were significant | |
| Method | Regression, Cox | |
| Comments | Stratified by intended treatment duration, adjusted for pre-treatment | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.198 | |
| Confidence Interval |
() 95% 0.096 to 0.405 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3659 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
2.0
0.3%
|
7.1
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | 4th test in a hierarchy, a p-value of less than 0.05 would be considered significant. If the previous tests in hierarchy were significant | |
| Method | Regression, Cox | |
| Comments | Stratified by intended treatment duration, adjusted for pre-treatment | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.278 | |
| Confidence Interval |
() 95% 0.146 to 0.528 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3274 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
1.2
0.2%
|
7.1
1.2%
|
| Title | Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
0.8
0.1%
|
5.2
0.9%
|
| Title | Percentage of Participants With Major Bleeding |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee (CIAC) blinded to treatment. Major bleeding event was overt bleeding associated with a 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Treatment-emergent [after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)] events and all events post randomization were reported. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of study treatment. For this population, participants were analyzed according to the treatment they received. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 598 | 590 |
| Treatment-emergent (time window: 2 days) |
0.7
0.1%
|
0.0
0%
|
| All post-randomization |
0.7
0.1%
|
0.2
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing), comparison was done for the treatment emergent (within two days after end of treatment) bleeding events. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1121 |
| Comments | No adjustment for multiple comparison. | |
| Method | Log Rank | |
| Comments | ||
| Title | Percentage of Participants With Clinically Relevant Bleeding |
|---|---|
| Description | All events adjudicated/confirmed by CIAC blinded to treatment. Clinically relevant bleeding included major bleeding (definition: see outcome 7) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of daily life activities. Treatment-emergent events (after intake of 1st study medication tablet as randomized up to 2 days after stop of study medication ['time window: 2 days']) and all events post randomization were reported |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of study treatment. For this population, participants were analyzed according to the treatment they received. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 598 | 590 |
| Treatment-emergent (time window: 2 days) |
6.0
1%
|
1.2
0.2%
|
| All post-randomization |
6.0
1%
|
1.9
0.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rivaroxaban (Xarelto, BAY59-7939), Placebo |
|---|---|---|
| Comments | The rivaroxaban to comparator hazard ratio was computed with a 95% CI (two-sided testing), comparison was done for the treatment emergent (within two days after end of treatment) bleeding events. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | No adjustment for multiple comparison, a p-value of less than 0.05 would be considered significant. | |
| Method | Regression, Cox | |
| Comments | Stratified by intended treatment duration, adjusted for pre-treatment done for treatment-emergent (time window: 2 days) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 5.185 | |
| Confidence Interval |
() 95% 2.307 to 11.652 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4131 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With All Death |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries. Treatment-emergent events and all events post randomization were reported. Treatment-emergent: after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days) |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of study treatment. For this population, participants were analyzed according to the treatment they received. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 598 | 590 |
| Treatment-emergent (time window: 2 days) |
0.2
0%
|
0.2
0%
|
| All post-randomization |
0.2
0%
|
0.3
0.1%
|
| Title | Percentage of Participants With Other Vascular Events |
|---|---|
| Description | All pre-defined vascular events (acute coronary syndromes, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism and vascular death) were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on results/films/images of confirmatory testing, and/or case summaries. On treatment events and all events post randomization were reported. On treatment: after intake of first tablet of study medication as randomized but not more than 1 day after stop of study medication (referred to as time window: 1 day) |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The valid-for-safety analysis population consisted of all participants who were randomized with valid informed consent and received at least one dose of study treatment. For this population, participants were analyzed according to the treatment they received. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 598 | 590 |
| On treatment (time window: 1 day) |
0.5
0.1%
|
0.7
0.1%
|
| All post-randomization |
0.8
0.1%
|
0.7
0.1%
|
| Title | Percentage of Participants With Death (PE) Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
0.0
0%
|
0.2
0%
|
| Title | Percentage of Participants With Death (PE Cannot be Excluded) Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
0.2
0%
|
0.0
0%
|
| Title | Percentage of Participants With Symptomatic Recurrent PE Until the Intended End of Study Treatment |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 6- or 12-month study treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized participants with valid informed consent. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 602 | 594 |
| Number [Percentage of participants] |
0.3
0%
|
2.2
0.4%
|
| Title | Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
1.2
0.2%
|
0.9
0.2%
|
| Title | Percentage of Participants With Symptomatic Recurrent PE During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either spiral computed tomography (CT) scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
0.3
0%
|
0.2
0%
|
| Title | Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
1.2
0.2%
|
1.1
0.2%
|
| Title | Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
1.4
0.2%
|
1.1
0.2%
|
| Title | Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events During Observational Period |
|---|---|
| Description | Events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral CT scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units, occurring in a critical site or contributing to death. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
1.2
0.2%
|
0.9
0.2%
|
| Title | Percentage of Participants With Recurrent VTE (PE or DVT) During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
1.2
0.2%
|
0.9
0.2%
|
| Title | Percentage of Participants With Recurrent DVT During Observational Period |
|---|---|
| Description | All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound or venography, results/films/images of confirmatory testing, and/or case summaries. |
| Time Frame | 30 days observational period after last intake of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention-to-treat (ITT) population entering observational period. Participants were analyzed according to the treatment assigned at randomization. |
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo |
|---|---|---|
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily |
| Measure Participants | 577 | 559 |
| Number [Percentage of participants] |
0.9
0.1%
|
0.7
0.1%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Rivaroxaban (Xarelto, BAY59-7939) | Placebo | ||
| Arm/Group Description | Participants were to receive rivaroxaban 20 mg oral tablet once daily | Participants were to receive matching placebo oral tablet once daily | ||
All Cause Mortality |
||||
| Rivaroxaban (Xarelto, BAY59-7939) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Rivaroxaban (Xarelto, BAY59-7939) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 59/598 (9.9%) | 52/590 (8.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Angina unstable | 3/598 (0.5%) | 0/590 (0%) | ||
| Atrial fibrillation | 3/598 (0.5%) | 4/590 (0.7%) | ||
| Bradycardia | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Cardiac arrest | 1/598 (0.2%) | 0/590 (0%) | ||
| Cardiac failure | 0/598 (0%) | 1/590 (0.2%) | ||
| Cardiac failure congestive | 1/598 (0.2%) | 0/590 (0%) | ||
| Cardiomyopathy | 0/598 (0%) | 1/590 (0.2%) | ||
| Sick sinus syndrome | 0/598 (0%) | 1/590 (0.2%) | ||
| Supraventricular tachycardia | 0/598 (0%) | 1/590 (0.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Abdominal pain upper | 2/598 (0.3%) | 0/590 (0%) | ||
| Colitis | 0/598 (0%) | 1/590 (0.2%) | ||
| Colitis ischaemic | 0/598 (0%) | 1/590 (0.2%) | ||
| Constipation | 0/598 (0%) | 1/590 (0.2%) | ||
| Diverticulum | 0/598 (0%) | 1/590 (0.2%) | ||
| Gastric ulcer | 1/598 (0.2%) | 0/590 (0%) | ||
| Gastritis | 1/598 (0.2%) | 0/590 (0%) | ||
| Gastrointestinal haemorrhage | 2/598 (0.3%) | 0/590 (0%) | ||
| Haemorrhoids | 0/598 (0%) | 1/590 (0.2%) | ||
| Inguinal hernia | 0/598 (0%) | 1/590 (0.2%) | ||
| Intestinal obstruction | 1/598 (0.2%) | 0/590 (0%) | ||
| Large intestinal ulcer | 0/598 (0%) | 1/590 (0.2%) | ||
| Melaena | 1/598 (0.2%) | 0/590 (0%) | ||
| Rectal haemorrhage | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Abdominal hernia obstructive | 0/598 (0%) | 1/590 (0.2%) | ||
| General disorders | ||||
| Asthenia | 0/598 (0%) | 1/590 (0.2%) | ||
| Chest pain | 2/598 (0.3%) | 3/590 (0.5%) | ||
| Non-cardiac chest pain | 0/598 (0%) | 1/590 (0.2%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Cholelithiasis | 1/598 (0.2%) | 0/590 (0%) | ||
| Immune system disorders | ||||
| Antiphospholipid syndrome | 1/598 (0.2%) | 0/590 (0%) | ||
| Infections and infestations | ||||
| Appendicitis | 1/598 (0.2%) | 0/590 (0%) | ||
| Bronchitis | 0/598 (0%) | 3/590 (0.5%) | ||
| Cellulitis | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Gastroenteritis | 2/598 (0.3%) | 0/590 (0%) | ||
| Herpes zoster | 0/598 (0%) | 1/590 (0.2%) | ||
| Intestinal gangrene | 0/598 (0%) | 1/590 (0.2%) | ||
| Localised infection | 1/598 (0.2%) | 0/590 (0%) | ||
| Lung abscess | 1/598 (0.2%) | 0/590 (0%) | ||
| Pharyngitis | 0/598 (0%) | 1/590 (0.2%) | ||
| Pneumonia | 3/598 (0.5%) | 0/590 (0%) | ||
| Urinary tract infection | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Postoperative abscess | 1/598 (0.2%) | 0/590 (0%) | ||
| Abdominal abscess | 1/598 (0.2%) | 0/590 (0%) | ||
| Respiratory tract infection | 1/598 (0.2%) | 0/590 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Humerus fracture | 0/598 (0%) | 1/590 (0.2%) | ||
| Joint dislocation | 1/598 (0.2%) | 0/590 (0%) | ||
| Rib fracture | 1/598 (0.2%) | 0/590 (0%) | ||
| Soft tissue injury | 0/598 (0%) | 1/590 (0.2%) | ||
| Drug exposure during pregnancy | 0/598 (0%) | 1/590 (0.2%) | ||
| Traumatic fracture | 0/598 (0%) | 1/590 (0.2%) | ||
| Post procedural haemorrhage | 1/598 (0.2%) | 0/590 (0%) | ||
| Skull fracture | 1/598 (0.2%) | 0/590 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 2/598 (0.3%) | 0/590 (0%) | ||
| Aspartate aminotransferase increased | 2/598 (0.3%) | 0/590 (0%) | ||
| Liver function test abnormal | 0/598 (0%) | 1/590 (0.2%) | ||
| Hepatic enzyme increased | 2/598 (0.3%) | 0/590 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetic ketoacidosis | 0/598 (0%) | 1/590 (0.2%) | ||
| Hyperglycaemia | 1/598 (0.2%) | 0/590 (0%) | ||
| Hyponatraemia | 1/598 (0.2%) | 0/590 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Costochondritis | 0/598 (0%) | 1/590 (0.2%) | ||
| Joint stiffness | 0/598 (0%) | 1/590 (0.2%) | ||
| Osteoarthritis | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Pain in extremity | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Rheumatoid arthritis | 1/598 (0.2%) | 1/590 (0.2%) | ||
| Musculoskeletal chest pain | 0/598 (0%) | 1/590 (0.2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma | 1/598 (0.2%) | 0/590 (0%) | ||
| Colon cancer | 0/598 (0%) | 1/590 (0.2%) | ||
| Endometrial cancer | 0/598 (0%) | 1/590 (0.2%) | ||
| Hepatic neoplasm | 1/598 (0.2%) | 0/590 (0%) | ||
| Malignant melanoma in situ | 0/598 (0%) | 1/590 (0.2%) | ||
| Metastases to liver | 1/598 (0.2%) | 0/590 (0%) | ||
| Metastases to spine | 1/598 (0.2%) | 0/590 (0%) | ||
| Sarcoma | 1/598 (0.2%) | 0/590 (0%) | ||
| Squamous cell carcinoma of skin | 1/598 (0.2%) | 0/590 (0%) | ||
| Benign vascular neoplasm | 0/598 (0%) | 1/590 (0.2%) | ||
| Colorectal cancer | 0/598 (0%) | 1/590 (0.2%) | ||
| Oesophageal neoplasm | 1/598 (0.2%) | 0/590 (0%) | ||
| Vaginal neoplasm | 0/598 (0%) | 1/590 (0.2%) | ||
| Metastatic squamous cell carcinoma | 1/598 (0.2%) | 0/590 (0%) | ||
| Nervous system disorders | ||||
| Epilepsy | 2/598 (0.3%) | 1/590 (0.2%) | ||
| Syncope | 2/598 (0.3%) | 1/590 (0.2%) | ||
| Transient ischaemic attack | 1/598 (0.2%) | 0/590 (0%) | ||
| Ischaemic stroke | 0/598 (0%) | 1/590 (0.2%) | ||
| Metabolic encephalopathy | 1/598 (0.2%) | 0/590 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion missed | 1/598 (0.2%) | 0/590 (0%) | ||
| Pregnancy | 1/598 (0.2%) | 0/590 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 0/598 (0%) | 1/590 (0.2%) | ||
| Depression | 1/598 (0.2%) | 0/590 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/598 (0.2%) | 0/590 (0%) | ||
| Hydronephrosis | 0/598 (0%) | 1/590 (0.2%) | ||
| Renal failure acute | 1/598 (0.2%) | 0/590 (0%) | ||
| Reproductive system and breast disorders | ||||
| Menometrorrhagia | 1/598 (0.2%) | 0/590 (0%) | ||
| Metrorrhagia | 1/598 (0.2%) | 0/590 (0%) | ||
| Vaginal prolapse | 0/598 (0%) | 1/590 (0.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/598 (0.2%) | 0/590 (0%) | ||
| Bronchospasm | 1/598 (0.2%) | 0/590 (0%) | ||
| Chronic obstructive pulmonary disease | 3/598 (0.5%) | 0/590 (0%) | ||
| Dyspnoea | 2/598 (0.3%) | 0/590 (0%) | ||
| Pulmonary embolism | 0/598 (0%) | 1/590 (0.2%) | ||
| Respiratory failure | 0/598 (0%) | 1/590 (0.2%) | ||
| Sleep apnoea syndrome | 0/598 (0%) | 1/590 (0.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Stevens-Johnson syndrome | 0/598 (0%) | 1/590 (0.2%) | ||
| Surgical and medical procedures | ||||
| Anal fistula excision | 0/598 (0%) | 1/590 (0.2%) | ||
| Appendicectomy | 1/598 (0.2%) | 0/590 (0%) | ||
| Bladder calculus removal | 1/598 (0.2%) | 0/590 (0%) | ||
| Vascular disorders | ||||
| Circulatory collapse | 1/598 (0.2%) | 0/590 (0%) | ||
| Haematoma | 0/598 (0%) | 1/590 (0.2%) | ||
| Hypertension | 2/598 (0.3%) | 1/590 (0.2%) | ||
| Thrombophlebitis | 1/598 (0.2%) | 0/590 (0%) | ||
| Peripheral arterial occlusive disease | 0/598 (0%) | 1/590 (0.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Rivaroxaban (Xarelto, BAY59-7939) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 63/598 (10.5%) | 65/590 (11%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 33/598 (5.5%) | 32/590 (5.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 31/598 (5.2%) | 38/590 (6.4%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | BAYER |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT00439725
Other Study ID Numbers:
- 11899
- 2006-004494-96
First Posted:
Feb 26, 2007
Last Update Posted:
Nov 4, 2014
Last Verified:
Oct 1, 2014