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Study of Apixaban for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00371683
Collaborator
(none)
3,608
Enrollment
107
Locations
2
Arms
18
Duration (Months)
33.7
Patients Per Site
1.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to learn if apixaban can prevent blood clots in the leg (deep vein Thrombosis [DVT]) and lung (pulmonary embolism [PE]) that sometimes occur after knee replacement surgery and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.

Condition or Disease Intervention/Treatment Phase
  • Drug: Enoxaparin + Placebo
  • Drug: Apixaban + Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
3608 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Phase 3 Randomized, Double-Blind Active-Controlled (Enoxaparin), Parallel-Group, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
Study Start Date :
Nov 1, 2006
Actual Primary Completion Date :
May 1, 2008
Actual Study Completion Date :
May 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: A1

+ placebo

Drug: Enoxaparin + Placebo
Syringes + tablets, Subcutaneous + Oral, 30mg, twice daily, 12 day treatment period
Other Names:
  • Lovenox®

    		•
    Experimental: A2

    + placebo

    Drug: Apixaban + Placebo
    Tablet + Syringes, Oral + subcutaneous, 2.5 mg, twice daily, 12 day treatment period

    Outcome Measures

    Primary Outcome Measures

    1. Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      An Independent Central Adjudication Committee (ICAC) adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). Surgery=Day 1; Randomization/Treatment started on Day of Surgery or the next day (Day 1 or Day 2). A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. Intended Treatment Period=starts on the day of randomization; for treated participants, the period ends at the latter of 2 days after last dose of study drug or 14 days after the first dose of study drug; for randomized participants who were not treated, the period ends 14 days after randomization.

    2. Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population [First dose of study drug to last dose, plus 2 days post last dose]

      ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Clinically relevant (CR); Non-Major (N-M) Bleeding. Day 1=Day of surgery. Treatment started (first dose) day of surgery or next day. Treatment continued for 12 days.

    3. Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period [Last dose of study drug to Day 72 (60 days)]

      ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Follow up Period was from the end of the treatment period (last dose) up to 60 days post last dose, Day 72.

    Secondary Outcome Measures

    1. Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected proximal DVT and non-fatal PE, and all-cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%).

    2. Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      VTE / VTE-related death was defined as the combination of fatal or non-fatal PE, and symptomatic or asymptomatic DVT. A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    3. Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    4. Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    5. Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. VTE includes DVT and PE. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    6. Event Rate for Participants With All-Cause Death During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      Event rate was number of participants with all-cause death divided by the number of participant's analyzed (%).

    7. Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    8. Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    9. Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    10. Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated VTE, acute clinically overt bleeding events, suspected thrombocytopenia, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).

    11. Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      An ICAC adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).

    12. Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period [From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization]

      ICAC adjudicated all venograms and suspected symptomatic DVT. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).

    13. Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period [From first dose to last dose, plus 2 days (12 days, plus 2)]

      ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).

    14. Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period [Post last dose of study drug to Day 72 (60 days)]

      A 60-day follow-up period started after the last dose of study drug and continued until the End of Study Visit on Day 72 (60 days ± 3 days, after the last dose of study drug). Event rate was number of participants with the endpoint divided by the number of participants analyzed (%). ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per ISTH guidelines modified for surgical patients.

    15. Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population [First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)]

      AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

    16. Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period [Baseline to last dose of study drug, plus 2 days]

      Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Blood pressures (BP) were measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Systolic and diastolic pressures were measured in millimeters of mercury (mmHg).

    17. Mean Change From Baseline in Heart Rate During the Treatment Period [Baseline to last dose of study drug, plus 2 days]

      Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Heart rate was measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Heart rate was measured in beats per minute (bpm).

    18. Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period [First dose to last dose of study drug (12 days), plus 2 days]

      Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Hematology profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 2, 3, 4, 12 (end of treatment). Upper limit of normal (ULN); lower limit of normal (LLN). Platelet Count low: < 100,000/mm^3 (or < 100*109 cells/L). Erythrocytes low: < 0.75 *pre-dose. Hemoglobin low: > 2 g/dL decrease compared to pre-dose or Value ≤ 8 g/dL. Hematocrit low: < 0.75*pre-dose . Leukocytes: < 0.75*LLN or > 1.25* ULN, or if pre-dose < LLN then use < 0.8*predose or > ULN if pre-dose > ULN then use > 1.2*predose or < LLN. Lymphocytes (absolute): < 0.750*10^3 cells/µL or > 7.50*10^3 cells/ µL. Eosinophils (absolute) high: > 0.750*10^3 cells/µL. Basophils(absolute) high: > 400/mm^3 (or > 0.4*103 cells/µL). Monocytes (absolute) high: > 2000/mm^3 (or > 2*103 cells/µL). Neutrophils(absolute) high: < 1.0*103 cells/µL.

    19. Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period [First dose to last dose of study drug (12 days), plus 2 days]

      Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Bilirubin (direct) high: > 1.5*ULN. Total bilirubin: : > 2*ULN, Alanine Aminotransferase (ALT) high: > 3*ULN. Alkaline Phosphatase (ALP): > 2*ULN. Aspartate Aminotransferase (AST): > 3*ULN. Creatinine: > 1.5*ULN.

    20. Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period [First dose to last dose of study drug (12 days), plus 2 days]

      Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Potassium: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*predose or > ULN if pre-dose > ULN then use > 1.1*predose or < LLN. Calcium: < 0.8*LLN or > 1.2*ULN, or if pre-dose < LLN then use < 0.75*predose or > ULN If pre-dose > ULN then use > 1.25*predose or < LLN. Chloride: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*predose or > ULN if pre-dose > ULN then use > 1.1*predose or < LLN. Sodium: < 0.95*LLN or > 1.05*ULN, or if pre-dose < LLN then use < 0.95*predose or >ULN if pre-dose > ULN then use > 1.05*predose or < LLN. Bicarbonate: < 0.75*LLN or > 1.25*ULN, or if pre-dose < LLN then use < 0.75*predose or > ULN if pre-dose > ULN then use > 1.25*predose or < LLN.

    21. Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period [First dose to last dose of study drug (12 days), plus 2 days]

      Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Fasting Glucose: if pre-dose < LLN then use < 0.8*predose; or > ULN if pre-dose > ULN then use > 2.0*predose or <LLN. Total Protein: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use 0.9*predose or > ULN if pre-dose > ULN then use 1.1*predose or < LLN. Uric Acid: > 1.5*ULN, or if pre-dose > ULN then use > 2*predose. Creatine Kinase (CK): > 5*ULN.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Men and non-pregnant, non-breastfeeding women

    • 18 years or older

    • Scheduled for knee replacement surgery

    Key Exclusion Criteria:

    • hereditary or acquired bleeding disorders

    • clotting disorders

    • bleeding or high risk for bleeding

    • drugs that affect bleeding or coagulation

    • need for ongoing parenteral or oral anticoagulation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Capstone Clinical Trials, Inc Birmingham Alabama United States 35205
    2 Capstone Clinical Trials, Inc Birmingham Alabama United States 35209
    3 West Alabama Research, Inc. Tuscaloosa Alabama United States 35406
    4 Martin Bowen Hefley Orthopedics Little Rock Arkansas United States 72205
    5 Colorado Orthopedic Consultants, Pc Aurora Colorado United States 80012
    6 Colorado Joint Replacement Denver Colorado United States 80210
    7 Jdpmedical Research Denver Colorado United States 80230
    8 Orhtopaedic Physicians Of Colorado, P.C. Englewood Colorado United States 80113
    9 Orthopedics Assocs Of Hartford Hartford Connecticut United States 06106
    10 Anthony S. Unger, Md Washington District of Columbia United States 20006
    11 Bay Pines Va Medical Center Bay Pines Florida United States 33744
    12 Pab Clinical Research Brandon Florida United States 33511
    13 Jacksonville Center For Clinical Research Jacksonville Florida United States 32216
    14 Mark W. Hollmann, Md Orange City Florida United States 32763
    15 Jewett Orthopaedic Clinic Winter Park Florida United States 32789
    16 Atlanta Knee And Sports Medicine Decatur Georgia United States 30033
    17 Americana Orthopedics Boise Idaho United States 83702
    18 Intermountain Orthopaedics Boise Idaho United States 83702
    19 Bluegrass Orthopaedics/Bmr Lexington Kentucky United States 40509
    20 Charleston Orthopaedic Assocs. Charleston South Carolina United States 29414
    21 Kelsey Seybold Clinic Houston Texas United States 77025
    22 Bone & Joint Clinic Of Houston Houston Texas United States 77030
    23 Gill Orthopedic Center Lubbock Texas United States 79410
    24 Robert R. King, Md Lubbock Texas United States 79410
    25 Unlimited Research San Antonio Texas United States 78217
    26 Local Institution Capital Federal Buenos Aires Argentina 1012
    27 Local Institution Capital Federal Buenos Aires Argentina 1426
    28 Local Institution Buenos Aires Argentina 1280
    29 Local Institution Buenos Aires Argentina 1425
    30 Local Institution Buenos Aires Argentina 7540
    31 Local Institution Buenos Aires Argentina C1181
    32 Local Institution Cordoba Argentina 5000
    33 Local Institution Garran Australian Capital Territory Australia 2605
    34 Local Institution Camperdown New South Wales Australia NSW 2050
    35 Local Institution Caringbah New South Wales Australia 2229
    36 Local Institution Lismore New South Wales Australia 2480
    37 Local Institution Gold Coast Queensland Australia 4215
    38 Local Institution Adelaide South Australia Australia 5011
    39 Local Institution Bedford Park South Australia Australia 5042
    40 Local Institution Box Hill Victoria Australia 3128
    41 Local Institution Windsor Victoria Australia 3181
    42 Local Institution Perth Western Australia Australia 6001
    43 Local Institution Curitiba Parana Brazil 80060
    44 Local Institution Porto Alegre, Rs Rio Grande Do Sul Brazil 90020
    45 Local Institution Porto Alegre Rio Grande Do Sul Brazil 90035
    46 Local Institution Campinas Sao Paulo Brazil 13083
    47 Local Institution Sao Paulo Brazil 05403
    48 Local Institution Edmonton Alberta Canada T6G 2R7
    49 Local Institution Ajax Ontario Canada L1S 2J5
    50 Local Institution Burlington Ontario Canada L7R 4B7
    51 Local Institution Cambridge Ontario Canada N1R 7L7
    52 Local Institution Chatham Ontario Canada N7L 4T1
    53 Local Institution Dartmouth Ontario Canada B2Y 2N6
    54 Local Institution Guelph Ontario Canada N1E 6L9
    55 Local Institution Lindsay Ontario Canada K9V 4M8
    56 Local Institution Newmarket Ontario Canada L3Y 5G8
    57 Local Institution Niagara Falls Ontario Canada L2E 6X2
    58 Local Institution Sarnia Ontario Canada N7T 6H3
    59 Local Institution Scarborough Ontario Canada M1S 4T7
    60 Local Institution Scarborough Ontario Canada M3C 1W3
    61 Local Institution St. Catharines Ontario Canada L2R 7P3
    62 Local Institution Stratford Ontario Canada N5A 2N4
    63 Local Institution Waterloo Ontario Canada N2J 1C4
    64 Local Institution Windsor Ontario Canada N8W 1E6
    65 Local Institution Charlottetown Prince Edward Island Canada C1A 1L2
    66 Local Institution Montreal Quebec Canada H4J 1C5
    67 Local Institution Quebec Canada G1L 3L5
    68 Local Institution Horsholm Denmark 2970
    69 Local Institution Kopenhamn S Denmark 2300
    70 Local Institution Kecskemet Hungary 6000
    71 Local Institution Szekesfehervar Hungary 8000
    72 Local Institution Szolnok Hungary 5008
    73 Local Institution Afula Israel 18101
    74 Local Institution Beer-Sheva Israel 84101
    75 Local Institution Haifa Israel 31096
    76 Local Institution Holon Israel 58100
    77 Local Institution Kfar-Saba Israel 44281
    78 Local Institution Petach-Tikva Israel 49100
    79 Local Institution Rehovot Israel 76100
    80 Local Institution Zerifin Israel 70300
    81 Local Institution Tijuana Baja California Mexico 22010
    82 Local Institution Df Distrito Federal Mexico 01030
    83 Local Institution Df Distrito Federal Mexico 05300
    84 Local Institution Df Distrito Federal Mexico 07760
    85 Local Institution Guadalajara Jalisco Mexico 44280
    86 Local Institution Monterrey Nuevo Leon Mexico 64000
    87 Local Institution Monterrey Nuevo Leon Mexico 64460
    88 Local Institution Cd Madero Tamaulipas Mexico 89240
    89 Local Institution Jalapa Veracruz Mexico 91020
    90 Local Institution Merida Yucatan Mexico 97070
    91 Local Institution Merida Yucatan Mexico 97133
    92 Local Institution Chihuahua Mexico 31000
    93 Local Institution Bialystok Poland 15276
    94 Local Institution Krakow Poland 31-826
    95 Local Institution Lodz Poland 91002
    96 Local Institution Lublin Poland 20954
    97 Local Institution Szczecin Poland 71252
    98 Local Institution Warszawa Poland 00909
    99 Local Institution Warszawa Poland 02005
    100 Local Institution Moscow Russian Federation 117333
    101 Local Institution Samara Russian Federation 443095
    102 Local Institution St. Petersburg Russian Federation 195257
    103 Local Institution Goteborg Sweden 416 85
    104 Local Institution Adana Turkey 01330
    105 Local Institution Bursa Turkey 16059
    106 Local Institution Mersin Turkey 33163
    107 Local Institution Trabzon Turkey 61030

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    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:
    NCT00371683
    Other Study ID Numbers:
    • CV185-034
    First Posted:
    Sep 4, 2006
    Last Update Posted:
    Dec 30, 2015
    Last Verified:
    Nov 1, 2015
    Keywords provided by Bristol-Myers Squibb
    Prevention of deep vein thrombosis and pulmonary embolism after total knee replacement surgery
    Additional relevant MeSH terms:
    Pulmonary Embolism
    Thrombosis
    Embolism
    Venous Thrombosis
    Enoxaparin
    Apixaban

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 3608 patients enrolled and 3195 were randomized to double blind (DB) Treatment Period: 413 not randomized due to: 227 no longer met criteria, 109 withdrew consent, 60 other reasons, 11 administrative reason by sponsor, 5 adverse event, 1 poor, non-compliance.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug (day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug(day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).
    Period Title: DB Treatment Period-Randomized Patients
    STARTED 1599 1596
    COMPLETED 1509 1489
    NOT COMPLETED 90 107
    Period Title: DB Treatment Period-Randomized Patients
    STARTED 1553 1533
    COMPLETED 1492 1461
    NOT COMPLETED 61 72

    Baseline Characteristics

    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours Total
    Arm/Group Description Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). Total of all reporting groups
    Overall Participants 1599 1596 3195
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.9
    (9.26)
    65.7
    (9.22)
    65.8
    (9.24)
    Age, Customized (participants) [Number]
    Less than(<) 65 years
    697
    43.6%
    691
    43.3%
    1388
    43.4%
    Greater than, equal to (>=) 65 and < 75 years
    593
    37.1%
    610
    38.2%
    1203
    37.7%
    >=75 years
    309
    19.3%
    295
    18.5%
    604
    18.9%
    Sex: Female, Male (Count of Participants)
    Female
    997
    62.4%
    986
    61.8%
    1983
    62.1%
    Male
    602
    37.6%
    610
    38.2%
    1212
    37.9%
    Region of Enrollment (participants) [Number]
    Argentina
    43
    2.7%
    43
    2.7%
    86
    2.7%
    Russian Federation
    15
    0.9%
    13
    0.8%
    28
    0.9%
    Hungary
    28
    1.8%
    26
    1.6%
    54
    1.7%
    United States
    464
    29%
    474
    29.7%
    938
    29.4%
    Canada
    554
    34.6%
    548
    34.3%
    1102
    34.5%
    Sweden
    66
    4.1%
    68
    4.3%
    134
    4.2%
    Turkey
    12
    0.8%
    10
    0.6%
    22
    0.7%
    Denmark
    87
    5.4%
    89
    5.6%
    176
    5.5%
    Brazil
    42
    2.6%
    39
    2.4%
    81
    2.5%
    Poland
    35
    2.2%
    35
    2.2%
    70
    2.2%
    Mexico
    138
    8.6%
    138
    8.6%
    276
    8.6%
    Israel
    44
    2.8%
    42
    2.6%
    86
    2.7%
    Australia
    50
    3.1%
    54
    3.4%
    104
    3.3%
    Norway
    21
    1.3%
    17
    1.1%
    38
    1.2%

    Outcome Measures

    1. Primary Outcome
    Title Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects
    Description An Independent Central Adjudication Committee (ICAC) adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). Surgery=Day 1; Randomization/Treatment started on Day of Surgery or the next day (Day 1 or Day 2). A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. Intended Treatment Period=starts on the day of randomization; for treated participants, the period ends at the latter of 2 days after last dose of study drug or 14 days after the first dose of study drug; for randomized participants who were not treated, the period ends 14 days after randomization.
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Primary Population=All randomized participants who: have an adjudicated and evaluable bilateral venogram performed during the Intended Treatment Period; or have an adjudicated VTE during the Intended Treatment Period; or die due to any cause during the Intended Treatment Period.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1157 1130
    Number (95% Confidence Interval) [percentage of participants]
    8.99
    0.6%
    8.85
    0.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Two criteria were to be met to demonstrate non-inferiority: the upper bound of the 95% confidence interval (CI) for the Relative Risk should be < 1.25, and the upper bound of the 95% CI for the risk difference should be < 5.6%.
    Statistical Test of Hypothesis p-Value 0.0635
    Comments If p-value is less than 0.025, it is statistically significant.
    Method t-test, 1 sided
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.78 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Two criteria were to be met to demonstrate non-inferiority: the upper bound of the 95% CI for the relative risk should be < 1.25, and the upper bound of the 95% CI for the risk difference should be < 5.6%.
    Statistical Test of Hypothesis p-Value <0.0001
    Comments If p-value is less than 0.025, it is statistically significant.
    Method t-test, 1 sided
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.11
    Confidence Interval (2-Sided) 95%
    -2.22 to 2.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period
    Description A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected proximal DVT and non-fatal PE, and all-cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated non-fatal PE or death, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1269 1216
    Number (95% Confidence Interval) [percentage of participants]
    2.05
    0.1%
    1.64
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    0.70 to 2.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments If the upper bound of the two-sided 95% CI for the Relative Risk was < 1 then superiority for the key secondary efficacy endpoint was demonstrated.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.36
    Confidence Interval (2-Sided) 95%
    -0.68 to 1.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7779
    Comments
    Method t-test, 1 sided
    Comments
    3. Secondary Outcome
    Title Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period
    Description VTE / VTE-related death was defined as the combination of fatal or non-fatal PE, and symptomatic or asymptomatic DVT. A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ±2 days.
    Measure Participants 1156 1127
    Number (95% Confidence Interval) [percentage of participants]
    8.91
    0.6%
    8.61
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.80 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.28
    Confidence Interval (2-Sided) 95%
    -2.04 to 2.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7754
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    4. Secondary Outcome
    Title Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period
    Description An ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1268 1213
    Number (95% Confidence Interval) [percentage of participants]
    1.97
    0.1%
    1.40
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.41
    Confidence Interval (2-Sided) 95%
    0.77 to 2.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    -0.47 to 1.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2626
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    5. Secondary Outcome
    Title Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ±2 days.
    Measure Participants 1270 1219
    Number (95% Confidence Interval) [percentage of participants]
    2.13
    0.1%
    1.97
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    0.63 to 1.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.11
    Confidence Interval (2-Sided) 95%
    -0.99 to 1.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7700
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    6. Secondary Outcome
    Title Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated all venograms, suspected symptomatic DVT and PE, and cause of death. VTE includes DVT and PE. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1269 1216
    Number (95% Confidence Interval) [percentage of participants]
    2.05
    0.1%
    1.73
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.19
    Confidence Interval (2-Sided) 95%
    0.68 to 2.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.28
    Confidence Interval (2-Sided) 95%
    -0.78 to 1.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5443
    Comments
    Method test of equality
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    7. Secondary Outcome
    Title Event Rate for Participants With All-Cause Death During the Intended Treatment Period
    Description Event rate was number of participants with all-cause death divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    All Randomized participants were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1599 1596
    Number (95% Confidence Interval) [percentage of participants]
    0.19
    0%
    0.19
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.20 to 4.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9975
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    8. Secondary Outcome
    Title Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    All randomized participants were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days,± 2 days.
    Measure Participants 1599 1596
    Number (95% Confidence Interval) [percentage of participants]
    0.13
    0%
    0.00
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.13
    Confidence Interval (2-Sided) 95%
    -0.05 to 0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1578
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    9. Secondary Outcome
    Title Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    All randomized participants were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID) plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1599 1596
    Number (95% Confidence Interval) [percentage of participants]
    1.25
    0.1%
    1.00
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    0.65 to 2.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    -0.47 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated suspected symptomatic DVT and PE, and cause of death. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    All randomized participants were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1599 1596
    Number (95% Confidence Interval) [percentage of participants]
    1.19
    0.1%
    0.81
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.46
    Confidence Interval (2-Sided) 95%
    0.72 to 2.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.38
    Confidence Interval (2-Sided) 95%
    -0.30 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2873
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    11. Secondary Outcome
    Title Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period
    Description ICAC adjudicated VTE, acute clinically overt bleeding events, suspected thrombocytopenia, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1162 1141
    Number (95% Confidence Interval) [percentage of participants]
    9.90
    0.6%
    10.60
    0.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    0.74 to 1.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.83
    Confidence Interval (2-Sided) 95%
    -3.30 to 1.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6145
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    12. Secondary Outcome
    Title Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period
    Description An ICAC adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    All randomized participants: PE, Symptomatic DVT, Symptomatic Proximal DVT, Symptomatic Distal DVT. Randomized with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint: All DVT, Asymptomatic DVT. n=number analyzed in each category
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1599 1596
    PE (Fatal or Non-Fatal) (n=1599, 1596)
    1.00
    0.1%
    0.44
    0%
    Non-Fatal PE (n=1599, 1596)
    0.88
    0.1%
    0.44
    0%
    All DVT n=1142, 1122
    7.79
    0.5%
    8.20
    0.5%
    Symptomatic DVT (n=1599, 1596)
    0.19
    0%
    0.44
    0%
    Asymptomatic DVT (n=1139,1115)
    7.55
    0.5%
    7.62
    0.5%
    Symptomatic Proximal DVT (n=1599,1596)
    0.13
    0%
    0.19
    0%
    Symptomatic Distal DVT (n=1599,1596)
    0.06
    0%
    0.38
    0%
    13. Secondary Outcome
    Title Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period
    Description ICAC adjudicated all venograms and suspected symptomatic DVT. Event rate was number of participants with the endpoint divided by the number of participant's analyzed (%).
    Time Frame From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with either an adjudicated and evaluable bilateral proximal (or distal, as appropriate) venogram or an adjudicated event associated with the endpoint. n= number analyzed
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1254 1207
    Proximal DVT (n=1254, 1207)
    0.72
    0%
    0.91
    0.1%
    Distal DVT (n=1146, 1133)
    7.24
    0.5%
    8.03
    0.5%
    Asymptomatic Proximal DVT (n=1252, 1204)
    0.56
    0%
    0.66
    0%
    Asymptomatic Distal DVT (n=1145, 1127)
    7.16
    0.4%
    7.54
    0.5%
    14. Secondary Outcome
    Title Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period
    Description ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%).
    Time Frame From first dose to last dose, plus 2 days (12 days, plus 2)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug were analyzed (Treated Population).
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1596 1588
    MI/Stroke
    0.06
    0%
    0.31
    0%
    MI
    0.06
    0%
    0.25
    0%
    Stroke
    0.00
    0%
    0.13
    0%
    Thrombocytopenia
    0.00
    0%
    0.13
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of MI/Stroke. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -0.55 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of MI. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of Stroke. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of thrombocytopenia. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Primary Outcome
    Title Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population
    Description ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Clinically relevant (CR); Non-Major (N-M) Bleeding. Day 1=Day of surgery. Treatment started (first dose) day of surgery or next day. Treatment continued for 12 days.
    Time Frame First dose of study drug to last dose, plus 2 days post last dose

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug (Treated population).
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ±2 days.
    Measure Participants 1596 1588
    Major Bleeding (n=1596, 1588)
    0.69
    0%
    1.39
    0.1%
    CR N-M Bleeding (n=1596, 1588)
    2.19
    0.1%
    2.96
    0.2%
    Major or CR N-M Bleeding(n=1596, 1588)
    2.88
    0.2%
    4.28
    0.3%
    Any Bleeding (n=1596, 1588)
    5.33
    0.3%
    6.80
    0.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of Major Bleeding. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.81
    Confidence Interval (2-Sided) 95%
    -1.49 to -0.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Major Bleeding Endpoint
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0533
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of Clinically Relevant Non-Major Bleeding. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -0.77
    Confidence Interval (2-Sided) 95%
    -1.87 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Clinically relevant Non-Major Bleeding endpoint
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1709
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of Major or Clinically Relevant Non-Major Bleeding. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -1.46
    Confidence Interval (2-Sided) 95%
    -2.75 to -0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Major or Clinically Relevant Non-Major Bleeding endpoint.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0338
    Comments
    Method test of equality
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Adjusted difference of event rates of Any Bleeding. Type of surgery was taken into consideration as a stratification factor.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value -1.52
    Confidence Interval (2-Sided) 95%
    -3.18 to 0.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Apixaban 2.5mg BID, Enoxaparin 30 mg SC Injection q 12 Hours
    Comments Any Bleeding Endpoint.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0816
    Comments For descriptive purposes only, p-values were presented for the test of equality of event rates
    Method test of equality
    Comments
    16. Primary Outcome
    Title Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period
    Description ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Follow up Period was from the end of the treatment period (last dose) up to 60 days post last dose, Day 72.
    Time Frame Last dose of study drug to Day 72 (60 days)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug during the Treatment Period and entered the Follow-Up Period.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1563 1553
    Major Bleeding (n=1563, 1553)
    0.13
    0%
    0.13
    0%
    CR N-M Bleeding (n=1563, 1553)
    0.26
    0%
    0.45
    0%
    Major or CR N-M Bleeding (n=1563, 1553)
    0.38
    0%
    0.58
    0%
    Any Bleeding (n=1563, 1553)
    0.90
    0.1%
    1.29
    0.1%
    17. Secondary Outcome
    Title Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period
    Description A 60-day follow-up period started after the last dose of study drug and continued until the End of Study Visit on Day 72 (60 days ± 3 days, after the last dose of study drug). Event rate was number of participants with the endpoint divided by the number of participants analyzed (%). ICAC adjudicated acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke per ISTH guidelines modified for surgical patients.
    Time Frame Post last dose of study drug to Day 72 (60 days)

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of study drug and entered the Follow-Up period
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1563 1553
    MI/Stroke
    0.06
    0%
    0.06
    0%
    MI
    0.06
    0%
    0.06
    0%
    Stroke
    0.00
    0%
    0.00
    0%
    Thrombocytopenia
    0.00
    0%
    0.00
    0%
    18. Secondary Outcome
    Title Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population
    Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
    Time Frame First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug during the Treatment Period.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, plus or minus 2 days.
    Measure Participants 1596 1588
    SAE
    123
    7.7%
    123
    7.7%
    Bleeding AE
    110
    6.9%
    144
    9%
    AEs leading to discontinuation
    60
    3.8%
    58
    3.6%
    Deaths
    3
    0.2%
    5
    0.3%
    19. Secondary Outcome
    Title Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
    Description Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Blood pressures (BP) were measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Systolic and diastolic pressures were measured in millimeters of mercury (mmHg).
    Time Frame Baseline to last dose of study drug, plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had blood pressure measurements at baseline were summarized.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, plus or minus 2 days.
    Measure Participants 1577 1574
    Diastolic BP Day 1 (n=240, 237)
    -0.4
    (0.741)
    -0.9
    (0.738)
    Diastolic BP Day 2 (n=1577, 1574)
    1.7
    (0.301)
    1.5
    (0.305)
    Diastolic BP Day 3 (n=1489,1498)
    2.3
    (0.322)
    2.1
    (0.321)
    Diastolic BP Day 4 (n=127,134)
    0.6
    (1.217)
    0.3
    (1.104)
    Diastolic BP Day 12 (n=1495,1463)
    7.3
    (0.342)
    7.5
    (0.343)
    Systolic BP Day 1 (n=240,237)
    1.5
    (1.189)
    -0.7
    (1.303)
    Systolic BP Day 2 (n=1577,1574)
    5.4
    (0.505)
    4.2
    (0.518)
    Systolic BP Day 3 (n=1489,1498)
    4.7
    (0.536)
    4.3
    (0.555)
    Systolic BP Day 4 (n=127,134)
    2.8
    (2.129)
    1.4
    (1.871)
    Systolic BP Day 12 (n=1495,1463)
    9.1
    (0.543)
    8.9
    (0.562)
    20. Secondary Outcome
    Title Mean Change From Baseline in Heart Rate During the Treatment Period
    Description Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug (12 + 2 days). Baseline=measurement prior to first dose of study drug. Heart rate was measured during screening (pre-operative, post-operative) and in the treatment period on Days 1 (day of first dose), 2, 3, 4,12 (end of treatment). Heart rate was measured in beats per minute (bpm).
    Time Frame Baseline to last dose of study drug, plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had heart rate measurements at baseline were summarized.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1575 1574
    Heart Rate Day 1 (n=240,237)
    2.3
    (0.761)
    2.7
    (0.761)
    Heart Rate Day 2 (n=1575,1574)
    4.6
    (0.312)
    4.5
    (0.317)
    Heart Rate Day 3 (n=1490,1498)
    4.5
    (0.334)
    5.0
    (0.344)
    Heart Rate Day 4 (n=127,134)
    7.6
    (1.365)
    9.4
    (1.320)
    Heart Rate Day 12 (n=1495, 1462)
    -0.3
    (0.361)
    -0.1
    (0.375)
    21. Secondary Outcome
    Title Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period
    Description Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Hematology profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 2, 3, 4, 12 (end of treatment). Upper limit of normal (ULN); lower limit of normal (LLN). Platelet Count low: < 100,000/mm^3 (or < 100*109 cells/L). Erythrocytes low: < 0.75 *pre-dose. Hemoglobin low: > 2 g/dL decrease compared to pre-dose or Value ≤ 8 g/dL. Hematocrit low: < 0.75*pre-dose . Leukocytes: < 0.75*LLN or > 1.25* ULN, or if pre-dose < LLN then use < 0.8*predose or > ULN if pre-dose > ULN then use > 1.2*predose or < LLN. Lymphocytes (absolute): < 0.750*10^3 cells/µL or > 7.50*10^3 cells/ µL. Eosinophils (absolute) high: > 0.750*10^3 cells/µL. Basophils(absolute) high: > 400/mm^3 (or > 0.4*103 cells/µL). Monocytes (absolute) high: > 2000/mm^3 (or > 2*103 cells/µL). Neutrophils(absolute) high: < 1.0*103 cells/µL.
    Time Frame First dose to last dose of study drug (12 days), plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days,± 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1583 1572
    Hemoglobin low (n=1561,1549)
    386
    24.1%
    392
    24.6%
    Hematocrit low (n=1558,1547)
    135
    8.4%
    157
    9.8%
    Platelet count low (n=1556,1543)
    6
    0.4%
    9
    0.6%
    Erythrocytes low (n=1557,1547)
    130
    8.1%
    149
    9.3%
    Leukocytes low(n=1583,1572)
    8
    0.5%
    11
    0.7%
    Leukocytes high(n=1583,1572)
    214
    13.4%
    210
    13.2%
    Basophils high (n=1577, 1564)
    0
    0%
    2
    0.1%
    Eosinophils high (n=1577, 1564)
    32
    2%
    13
    0.8%
    Lymphocytes low (n=1577,1564)
    125
    7.8%
    117
    7.3%
    Lymphocytes high (n=1577,1564)
    2
    0.1%
    4
    0.3%
    Monocytes high (n=1577,1564)
    4
    0.3%
    4
    0.3%
    Neutrophils low (n=1577,1564)
    4
    0.3%
    5
    0.3%
    22. Secondary Outcome
    Title Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period
    Description Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Bilirubin (direct) high: > 1.5*ULN. Total bilirubin: : > 2*ULN, Alanine Aminotransferase (ALT) high: > 3*ULN. Alkaline Phosphatase (ALP): > 2*ULN. Aspartate Aminotransferase (AST): > 3*ULN. Creatinine: > 1.5*ULN.
    Time Frame First dose to last dose of study drug (12 days), plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID) plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 hours plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1573 1563
    ALP high (n=1573,1563)
    42
    2.6%
    55
    3.4%
    ALT high (n=1573,1562)
    33
    2.1%
    45
    2.8%
    AST high (n=1573,1562)
    29
    1.8%
    40
    2.5%
    Bilirubin direct high (n=1563,1553)
    63
    3.9%
    54
    3.4%
    Bilirubin total high(n=1572,1562)
    2
    0.1%
    8
    0.5%
    Creatinine high (n=1569,1562)
    17
    1.1%
    28
    1.8%
    23. Secondary Outcome
    Title Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period
    Description Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Potassium: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*predose or > ULN if pre-dose > ULN then use > 1.1*predose or < LLN. Calcium: < 0.8*LLN or > 1.2*ULN, or if pre-dose < LLN then use < 0.75*predose or > ULN If pre-dose > ULN then use > 1.25*predose or < LLN. Chloride: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*predose or > ULN if pre-dose > ULN then use > 1.1*predose or < LLN. Sodium: < 0.95*LLN or > 1.05*ULN, or if pre-dose < LLN then use < 0.95*predose or >ULN if pre-dose > ULN then use > 1.05*predose or < LLN. Bicarbonate: < 0.75*LLN or > 1.25*ULN, or if pre-dose < LLN then use < 0.75*predose or > ULN if pre-dose > ULN then use > 1.25*predose or < LLN.
    Time Frame First dose to last dose of study drug (12 days), plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days,± 2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
    Measure Participants 1569 1562
    Calcium low (n=1569,1562)
    1
    0.1%
    5
    0.3%
    Calcium high (n=1569,1562)
    0
    0%
    1
    0.1%
    Chloride low (n=1568,1562)
    11
    0.7%
    17
    1.1%
    Chloride high (n=1568,1562)
    0
    0%
    1
    0.1%
    Bicarbonate low (n=1568,1561)
    11
    0.7%
    13
    0.8%
    Potassium low(n=1568,1559)
    54
    3.4%
    56
    3.5%
    Potassium high(n=1568,1559)
    26
    1.6%
    20
    1.3%
    Sodium low (n=1568,1562)
    23
    1.4%
    39
    2.4%
    Sodium high (n=1568,1562)
    2
    0.1%
    0
    0%
    24. Secondary Outcome
    Title Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period
    Description Treatment Period=the period from first dose of study drug through 2 days after discontinuation of study drug. Laboratory Chemistry profile was measured during screening (pre-operative, post-operative) and in the Treatment Period on Days 4, and 12 (end of treatment). Fasting Glucose: if pre-dose < LLN then use < 0.8*predose; or > ULN if pre-dose > ULN then use > 2.0*predose or <LLN. Total Protein: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use 0.9*predose or > ULN if pre-dose > ULN then use 1.1*predose or < LLN. Uric Acid: > 1.5*ULN, or if pre-dose > ULN then use > 2*predose. Creatine Kinase (CK): > 5*ULN.
    Time Frame First dose to last dose of study drug (12 days), plus 2 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets BID plus matching placebo SC injection q 12 hours for 12 days, ±2 days. Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ±2 days.
    Measure Participants 1573 1563
    Fasting Glucose low (n=611, 579)
    8
    0.5%
    5
    0.3%
    Fasting Glucose high (n=611, 579)
    54
    3.4%
    28
    1.8%
    Total Protein low (n=1568,1562)
    527
    33%
    513
    32.1%
    CK high (n=1573,1563)
    52
    3.3%
    45
    2.8%
    Uric Acid high (n=1567,1562)
    22
    1.4%
    12
    0.8%

    Adverse Events

    Time Frame First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs.
    Adverse Event Reporting Description All participants who received at least one dose of study drug were included.
    Arm/Group Title Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Arm/Group Description Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72). Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).
    All Cause Mortality
    Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 123/1596 (7.7%) 123/1588 (7.7%)
    Blood and lymphatic system disorders
    Anaemia 5/1596 (0.3%) 2/1588 (0.1%)
    Coagulopathy 1/1596 (0.1%) 0/1588 (0%)
    Cardiac disorders
    Acute coronary syndrome 0/1596 (0%) 1/1588 (0.1%)
    Atrial fibrillation 3/1596 (0.2%) 5/1588 (0.3%)
    Cardiac failure congestive 1/1596 (0.1%) 0/1588 (0%)
    Cardiac arrest 0/1596 (0%) 1/1588 (0.1%)
    Myocardial infarction 2/1596 (0.1%) 4/1588 (0.3%)
    Arrhythmia 0/1596 (0%) 2/1588 (0.1%)
    Cardiac failure 1/1596 (0.1%) 0/1588 (0%)
    Acute myocardial infarction 0/1596 (0%) 1/1588 (0.1%)
    Bradycardia 1/1596 (0.1%) 1/1588 (0.1%)
    Supraventricular tachycardia 0/1596 (0%) 1/1588 (0.1%)
    Tachycardia 2/1596 (0.1%) 0/1588 (0%)
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage 1/1596 (0.1%) 0/1588 (0%)
    Diarrhoea 2/1596 (0.1%) 0/1588 (0%)
    Ileus 2/1596 (0.1%) 1/1588 (0.1%)
    Ileus paralytic 0/1596 (0%) 2/1588 (0.1%)
    Intestinal obstruction 2/1596 (0.1%) 0/1588 (0%)
    Small intestinal obstruction 1/1596 (0.1%) 0/1588 (0%)
    Gastrointestinal haemorrhage 2/1596 (0.1%) 5/1588 (0.3%)
    Melaena 0/1596 (0%) 1/1588 (0.1%)
    Haematemesis 0/1596 (0%) 1/1588 (0.1%)
    Nausea 1/1596 (0.1%) 1/1588 (0.1%)
    Abdominal pain upper 2/1596 (0.1%) 0/1588 (0%)
    General disorders
    Hernia 1/1596 (0.1%) 0/1588 (0%)
    Chest discomfort 0/1596 (0%) 1/1588 (0.1%)
    Therapeutic response decreased 0/1596 (0%) 1/1588 (0.1%)
    Chest pain 1/1596 (0.1%) 0/1588 (0%)
    Gait disturbance 0/1596 (0%) 1/1588 (0.1%)
    Oedema 0/1596 (0%) 1/1588 (0.1%)
    Bloody discharge 1/1596 (0.1%) 0/1588 (0%)
    Infusion site extravasation 1/1596 (0.1%) 0/1588 (0%)
    Multi-organ failure 1/1596 (0.1%) 0/1588 (0%)
    Impaired healing 0/1596 (0%) 2/1588 (0.1%)
    Secretion discharge 1/1596 (0.1%) 1/1588 (0.1%)
    Asthenia 1/1596 (0.1%) 0/1588 (0%)
    Death 0/1596 (0%) 1/1588 (0.1%)
    Swelling 2/1596 (0.1%) 0/1588 (0%)
    Discomfort 1/1596 (0.1%) 0/1588 (0%)
    Oedema peripheral 3/1596 (0.2%) 1/1588 (0.1%)
    Pyrexia 1/1596 (0.1%) 3/1588 (0.2%)
    Infections and infestations
    Infection 2/1596 (0.1%) 0/1588 (0%)
    Pyelonephritis 1/1596 (0.1%) 0/1588 (0%)
    Incision site infection 1/1596 (0.1%) 1/1588 (0.1%)
    Lobar pneumonia 1/1596 (0.1%) 0/1588 (0%)
    Septic shock 1/1596 (0.1%) 0/1588 (0%)
    Urinary tract infection 1/1596 (0.1%) 0/1588 (0%)
    Wound infection 4/1596 (0.3%) 2/1588 (0.1%)
    Cellulitis 4/1596 (0.3%) 2/1588 (0.1%)
    Post procedural infection 2/1596 (0.1%) 2/1588 (0.1%)
    Skin infection 1/1596 (0.1%) 0/1588 (0%)
    Gastroenteritis 0/1596 (0%) 2/1588 (0.1%)
    Localised infection 0/1596 (0%) 1/1588 (0.1%)
    Soft tissue infection 0/1596 (0%) 2/1588 (0.1%)
    Urosepsis 0/1596 (0%) 1/1588 (0.1%)
    Nasopharyngitis 1/1596 (0.1%) 0/1588 (0%)
    Paronychia 0/1596 (0%) 1/1588 (0.1%)
    Sepsis 1/1596 (0.1%) 1/1588 (0.1%)
    Haematoma infection 0/1596 (0%) 1/1588 (0.1%)
    Postoperative wound infection 0/1596 (0%) 1/1588 (0.1%)
    Arthritis infective 0/1596 (0%) 1/1588 (0.1%)
    Subcutaneous abscess 0/1596 (0%) 1/1588 (0.1%)
    Incision site cellulitis 1/1596 (0.1%) 1/1588 (0.1%)
    Pneumonia 4/1596 (0.3%) 1/1588 (0.1%)
    Post procedural cellulitis 2/1596 (0.1%) 0/1588 (0%)
    Injury, poisoning and procedural complications
    Incision site haemorrhage 0/1596 (0%) 1/1588 (0.1%)
    Patella fracture 0/1596 (0%) 1/1588 (0.1%)
    Post procedural complication 1/1596 (0.1%) 0/1588 (0%)
    Postoperative ileus 0/1596 (0%) 2/1588 (0.1%)
    Fall 2/1596 (0.1%) 0/1588 (0%)
    Fat embolism 1/1596 (0.1%) 0/1588 (0%)
    Ligament rupture 0/1596 (0%) 1/1588 (0.1%)
    Postoperative wound complication 0/1596 (0%) 1/1588 (0.1%)
    Wound secretion 0/1596 (0%) 1/1588 (0.1%)
    Wound dehiscence 1/1596 (0.1%) 1/1588 (0.1%)
    Ankle fracture 0/1596 (0%) 1/1588 (0.1%)
    Humerus fracture 1/1596 (0.1%) 0/1588 (0%)
    Overdose 2/1596 (0.1%) 2/1588 (0.1%)
    Anaemia postoperative 0/1596 (0%) 2/1588 (0.1%)
    Incision site erythema 1/1596 (0.1%) 0/1588 (0%)
    Joint dislocation 0/1596 (0%) 1/1588 (0.1%)
    Ligament injury 0/1596 (0%) 1/1588 (0.1%)
    Wrist fracture 0/1596 (0%) 1/1588 (0.1%)
    Incision site pain 1/1596 (0.1%) 0/1588 (0%)
    Medical device complication 1/1596 (0.1%) 1/1588 (0.1%)
    Accidental overdose 0/1596 (0%) 1/1588 (0.1%)
    Femur fracture 1/1596 (0.1%) 0/1588 (0%)
    Investigations
    Blood sodium decreased 1/1596 (0.1%) 0/1588 (0%)
    Heart rate increased 1/1596 (0.1%) 0/1588 (0%)
    Heart rate decreased 0/1596 (0%) 1/1588 (0.1%)
    Platelet count decreased 1/1596 (0.1%) 0/1588 (0%)
    Clostridium difficile toxin test positive 1/1596 (0.1%) 0/1588 (0%)
    Haemoglobin decreased 1/1596 (0.1%) 1/1588 (0.1%)
    Blood culture positive 0/1596 (0%) 1/1588 (0.1%)
    Hepatic enzyme increased 1/1596 (0.1%) 0/1588 (0%)
    Oxygen saturation decreased 1/1596 (0.1%) 3/1588 (0.2%)
    Weight decreased 1/1596 (0.1%) 0/1588 (0%)
    Metabolism and nutrition disorders
    Hypokalaemia 0/1596 (0%) 1/1588 (0.1%)
    Dehydration 1/1596 (0.1%) 2/1588 (0.1%)
    Hyponatraemia 0/1596 (0%) 2/1588 (0.1%)
    Hypoglycaemia 0/1596 (0%) 2/1588 (0.1%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 1/1596 (0.1%) 0/1588 (0%)
    Joint range of motion decreased 0/1596 (0%) 1/1588 (0.1%)
    Joint swelling 1/1596 (0.1%) 0/1588 (0%)
    Muscular weakness 1/1596 (0.1%) 0/1588 (0%)
    Arthralgia 1/1596 (0.1%) 1/1588 (0.1%)
    Joint contracture 1/1596 (0.1%) 0/1588 (0%)
    Joint stiffness 1/1596 (0.1%) 1/1588 (0.1%)
    Joint ankylosis 1/1596 (0.1%) 1/1588 (0.1%)
    Pain in extremity 3/1596 (0.2%) 2/1588 (0.1%)
    Nervous system disorders
    Transient ischaemic attack 1/1596 (0.1%) 0/1588 (0%)
    Cerebrovascular accident 0/1596 (0%) 4/1588 (0.3%)
    Haemorrhage intracranial 0/1596 (0%) 1/1588 (0.1%)
    Toxic encephalopathy 1/1596 (0.1%) 0/1588 (0%)
    Lethargy 1/1596 (0.1%) 0/1588 (0%)
    Syncope 1/1596 (0.1%) 2/1588 (0.1%)
    Paraesthesia 0/1596 (0%) 1/1588 (0.1%)
    Sedation 0/1596 (0%) 1/1588 (0.1%)
    Encephalopathy 0/1596 (0%) 1/1588 (0.1%)
    Psychiatric disorders
    Mania 1/1596 (0.1%) 0/1588 (0%)
    Suicide attempt 0/1596 (0%) 1/1588 (0.1%)
    Alcohol withdrawal syndrome 0/1596 (0%) 1/1588 (0.1%)
    Delirium tremens 1/1596 (0.1%) 0/1588 (0%)
    Depression 0/1596 (0%) 2/1588 (0.1%)
    Psychotic disorder 1/1596 (0.1%) 0/1588 (0%)
    Confusional state 1/1596 (0.1%) 1/1588 (0.1%)
    Renal and urinary disorders
    Urinary retention 1/1596 (0.1%) 1/1588 (0.1%)
    Calculus ureteric 1/1596 (0.1%) 0/1588 (0%)
    Hydronephrosis 1/1596 (0.1%) 0/1588 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/1596 (0.1%) 1/1588 (0.1%)
    Respiratory distress 1/1596 (0.1%) 1/1588 (0.1%)
    Atelectasis 1/1596 (0.1%) 1/1588 (0.1%)
    Dyspnoea exertional 1/1596 (0.1%) 0/1588 (0%)
    Dyspnoea 4/1596 (0.3%) 2/1588 (0.1%)
    Hypoxia 2/1596 (0.1%) 1/1588 (0.1%)
    Respiratory failure 1/1596 (0.1%) 0/1588 (0%)
    Asthma 1/1596 (0.1%) 0/1588 (0%)
    Respiratory arrest 0/1596 (0%) 1/1588 (0.1%)
    Pneumonia aspiration 1/1596 (0.1%) 1/1588 (0.1%)
    Pulmonary embolism 19/1596 (1.2%) 9/1588 (0.6%)
    Skin and subcutaneous tissue disorders
    Skin necrosis 0/1596 (0%) 1/1588 (0.1%)
    Blister 0/1596 (0%) 1/1588 (0.1%)
    Increased tendency to bruise 1/1596 (0.1%) 0/1588 (0%)
    Rash 0/1596 (0%) 1/1588 (0.1%)
    Vascular disorders
    Orthostatic hypotension 1/1596 (0.1%) 1/1588 (0.1%)
    Haematoma 3/1596 (0.2%) 4/1588 (0.3%)
    Haemorrhage 0/1596 (0%) 2/1588 (0.1%)
    Blood pressure fluctuation 1/1596 (0.1%) 0/1588 (0%)
    Vascular pseudoaneurysm 1/1596 (0.1%) 0/1588 (0%)
    Hypertension 2/1596 (0.1%) 0/1588 (0%)
    Wound haemorrhage 0/1596 (0%) 2/1588 (0.1%)
    Hypovolaemic shock 0/1596 (0%) 1/1588 (0.1%)
    Deep vein thrombosis 6/1596 (0.4%) 10/1588 (0.6%)
    Hypotension 2/1596 (0.1%) 1/1588 (0.1%)
    Other (Not Including Serious) Adverse Events
    Apixaban 2.5mg BID Enoxaparin 30 mg SC Injection q 12 Hours
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 713/1596 (44.7%) 741/1588 (46.7%)
    Gastrointestinal disorders
    Vomiting 99/1596 (6.2%) 102/1588 (6.4%)
    Nausea 208/1596 (13%) 241/1588 (15.2%)
    Constipation 227/1596 (14.2%) 234/1588 (14.7%)
    General disorders
    Oedema peripheral 131/1596 (8.2%) 153/1588 (9.6%)
    Pyrexia 137/1596 (8.6%) 149/1588 (9.4%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 84/1596 (5.3%) 77/1588 (4.8%)
    Nervous system disorders
    Dizziness 103/1596 (6.5%) 88/1588 (5.5%)
    Psychiatric disorders
    Insomnia 77/1596 (4.8%) 86/1588 (5.4%)
    Vascular disorders
    Deep vein thrombosis 127/1596 (8%) 113/1588 (7.1%)

    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
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00371683
    Other Study ID Numbers:
    • CV185-034
    First Posted:
    Sep 4, 2006
    Last Update Posted:
    Dec 30, 2015
    Last Verified:
    Nov 1, 2015