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Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)

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ClinicalTrials.gov Identifier: NCT00423319
Recruitment Status : Completed
First Posted : January 18, 2007
Results First Posted : May 14, 2014
Last Update Posted : May 14, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Deep Vein Thrombosis
Pulmonary Embolism
Interventions Drug: Enoxaparin
Drug: Apixaban
Drug: Enoxaparin-matching placebo
Drug: Apixaban-matching placebo
Enrollment 5407
Recruitment Details  
Pre-assignment Details A total of 5765 subjects were enrolled, and 5407 were randomized to double-blind study drug.
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD) Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Period Title: Overall Study
Started 2708 [1] 2699 [1]
Participants Who Received Treatment 2673 2659
Completed 2484 2447
Not Completed 224 252
Reason Not Completed
Death             2             0
Adverse Event             93             112
Withdrawal by Subject             86             99
Lost to Follow-up             4             3
Poor compliance or noncompliance             1             1
No longer meets study criteria             15             15
Not specified             23             22
[1]
Randomized
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo Total
Hide Arm/Group Description Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD) Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID Total of all reporting groups
Overall Number of Baseline Participants 2708 2699 5407
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2708 participants 2699 participants 5407 participants
60.9  (11.79) 60.6  (11.82) 60.8  (11.81)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2708 participants 2699 participants 5407 participants
Younger than 65 years 1608 1605 3213
65 to younger than 75 years 770 767 1537
75 years and older 330 327 657
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2708 participants 2699 participants 5407 participants
Female
1430
  52.8%
1451
  53.8%
2881
  53.3%
Male
1278
  47.2%
1248
  46.2%
2526
  46.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2708 participants 2699 participants 5407 participants
United States 450 441 891
Spain 32 29 61
Ukraine 217 219 436
Russian Federation 274 276 550
Israel 57 56 113
United Kingdom 77 78 155
India 56 56 112
France 75 74 149
Hungary 152 150 302
Mexico 73 74 147
Canada 359 356 715
Argentina 53 54 107
Belgium 59 60 119
Poland 184 185 369
Romania 24 25 49
Australia 101 99 200
Denmark 99 99 198
Germany 135 134 269
Norway 47 48 95
China 121 124 245
Sweden 63 62 125
1.Primary Outcome
Title Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period
Hide Description Event rate=Number of events divided by the number of patients evaluated. A mandatory bilateral ascending contrast venogram was to be obtained on Day 35 (± 3). Patients with confirmed symptomatic DVT at any time, or asymptomatic DVT upon venography, were to receive treatment for DVT according to the investigator’s standard of care. Signs and symptoms suggestive of VTE included, but were not limited to: 1) lower extremity DVT: erythema, warmth, pain, swelling, tenderness; and 2) PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended Treatment Period started on day of randomization and, for patients who received treatment, ended at the later of 2 days after last dose of study drug or 38 days after the first dose (presurgery) of study drug. For randomized patients who did not receive study drug, the period ended 38 days after randomization.
Time Frame Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who, during the Intended Treatment Period, had an adjudicated and evaluable bilateral venogram, had an adjudicated venous thromboembolic event, or died of any cause.
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 1949 1917
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of events/patients evaluated
1.39
(0.95 to 2.02)
3.86
(3.08 to 4.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistically significant at the 1-sided 0.025 level
Method Farrington-Manning test
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.22 to 0.54
Estimation Comments Apixaban-enoxaparin
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistically significant at the 1-sided 0.025 level
Method Farrington-Manning test
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference
Estimated Value -2.47
Confidence Interval (2-Sided) 95%
-3.54 to 1.50
Estimation Comments Apixaban-enoxaparin
2.Secondary Outcome
Title Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period
Hide Description Event rate=Number of events divided by the number of patients evaluated. Each patient was categorized as having no proximal DVT, having proximal DVT, being nonevaluable for proximal DVT, having no distal DVT, having distal DVT, or being nonevaluable for distal DVT. Adjudication criteria were: Normal=All deep veins were visualized, and there was no intraluminal filling defect (ILFD). ILFD=An area of reduced, or absent filling, at least partially surrounded with contrast medium in ≥ 2 projections or a lack of filling in a vessel in which there was a cut-off that had the configuration of a thrombus. Indeterminate=A lack of filling of a region of the deep vein system, proximal or distal, without the presence of an ILFD elsewhere in the same region. Not Done=A venography was not performed. Proximal DVT was found if any of the proximal veins had an ILFD. Pulmonary embolism was radiographically (angiography, V/Q scan, computed tomography) determined.
Time Frame Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with either an adjudicated event or an adjudicated evaluable bilateral venogram
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2199 2195
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of events/patients evaluated
0.45
(0.24 to 0.85)
1.14
(0.77 to 1.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistically significant at the 1-sided 0.025 level
Method Farrington-Manning test
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.15 to 0.80
Estimation Comments Apixaban-enoxaparin
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments Statistically significant at the 1-sided 0.025 level
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk difference
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-1.27 to -0.17
Estimation Comments Apixaban-enoxaparin
3.Secondary Outcome
Title Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period
Hide Description VTE=venous thromboembolic event; VTE-related death=combination of fatal or nonfatal PE and symptomatic or asymptomatic DVT. Event rate=Number of events divided by the number of patients evaluated.
Time Frame Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized to treatment
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2708 2699
Measure Type: Number
Unit of Measure: Percentage of events/patients evaluated
All-cause death 0.11 0.04
VTE-related death 0.04 0.00
PE (fatal or nonfatal) 0.11 0.19
Nonfatal PE 0.07 0.19
All DVT (n=1944, 1911) 1.13 3.56
Symptomatic DVT 0.04 0.19
Asymptomatic DVT (n=1943, 1907) 1.08 3.30
Proximal DVT (n=2196, 2190) 0.32 0.91
Distal DVT (1951, 1908) 1.03 2.99
Symptomatic proximal DVT 0.04 0.15
Asymptomatic proximal DVT (n=2195, 2187) 0.27 0.73
Symptomatic distal DVT 0.04 0.04
Asymptomatic distal DVT (n=1950, 1907) 0.97 2.94
4.Secondary Outcome
Title Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
Hide Description Event rate=Number of events divided by the number of patients evaluated. Major bleeding event defined as a bleeding event that was 1) Acute clinically overt bleeding accompanied by at least 1 of the following: decrease in hemoglobin of ≥ 2 g/dL over a 24-hour period, transfusion of ≥2 units of packed red blood cells; bleeding that occurred in at least 1 of the following sites: intracranial, intra-spinal, intraocular, pericardial, an operated joint and requires reoperation or intervention, intramuscular with compartment syndrome, or retroperitoneal; 2) Fatal. CRNM was defined as acute clinically overt bleeding that did not satisfy the criteria for a major bleeding event and met at least 1 of the following: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, or hemoptysis. Minor bleeding was defined as an acute clinically overt bleeding event that did not meet the criteria for major bleeding or a CRNM. Fatal bleeding event was defined as bleeding that was the primary
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of events/patients evaluted
Major bleeding
0.82
(0.54 to 1.25)
0.68
(0.42 to 1.08)
CRNM
4.08
(3.39 to 4.90)
4.51
(3.79 to 5.38)
Major or CRNM
4.83
(4.08 to 5.71)
5.04
(4.27 to 5.94)
Any bleeding
11.71
(10.55 to 12.99)
12.56
(11.36 to 13.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments 2-sided P-Value
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-0.33 to 0.64
Estimation Comments Major bleeding. Apixaban-enoxaparin
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments 2-sided P-Value
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-1.53 to 0.66
Estimation Comments CRNM. Apixaban-enoxaparin
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments 2-sided P-Value
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.38 to 0.95
Estimation Comments Major or CRNM. Apixaban-enoxaparin
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments 2-sided P-Value
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rate
Estimated Value -0.85
Confidence Interval (2-Sided) 95%
-2.61 to 0.90
Estimation Comments Any bleeding. Apixaban-enoxaparin
5.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
Hide 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. All suspected bleeding events were to be reported by the investigator as either an AE or SAE and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood.
Time Frame First dose of study drug (presurgery) through 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study medication
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
SAEs 18 18
Bleeding AEs 15 21
Death 2 0
6.Secondary Outcome
Title Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hide Description All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Postprocedural hematoma 20 23
Operative hemorrhage 19 14
Incision site hematoma 14 10
Incision site hemorrhage 13 19
Postprocedural hemorrhagic 4 7
Hematuria traumatic 1 1
Periorbital hematoma 1 0
Subcutaneous hematoma 1 0
Traumatic hematoma 0 1
Hematoma 34 38
Wound hemorrhage 18 15
Hemorrhage 13 13
Hematuria 41 39
Hemorrhage urinary tract 1 1
Urethral hemorrhage 0 2
Epistaxis 33 25
Hemoptysis 3 1
7.Secondary Outcome
Title Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Hide Description All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Bloody discharge 16 13
Catheter site hemorrhage 6 5
Injection site hemorrhage 4 10
Injection site hematoma 3 28
Infusion site hematoma 1 0
Vessel puncture site hematoma 1 0
Hematocrit decreased 18 21
Red blood cell count decreased 14 20
Blood urine present 8 6
Blood urine 1 1
Occult blood positive 1 0
Fibrin D dimer increased 0 1
Hematochezia 6 2
Mallory-Weiss Syndrome 4 0
Hematemesis 3 2
Melaena 3 1
Rectal hemorrhage 3 1
Gingival bleeding 2 3
Anal hemorrhage 1 0
Diarrhea hemorrhagic 1 0
Diverticulum intestinal hemorrhagic 1 0
Gastrointestinal hemorrhage 1 1
Intra-abdominal hematoma 1 0
Duodenal ulcer hemorrhage 0 1
Hemorrhoidal hemorrhage 0 1
Mouth hemorrhage 0 1
8.Secondary Outcome
Title Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Hide Description All suspected bleeding events were to be reported by the investigator as either an adverse event or serious adverse event or and adjudicated by the Independent Central Adjudication Committee (ICAC). Definitions of bleeding outcomes: Acute clinically overt bleeding =new onset, visible bleeding, or signs or symptoms suggestive of bleeding with confirmatory imaging techniques that could detect the presence of blood. All acute clinically overt bleeding events were adjudicated by the ICAC as a major bleeding event or a clinically relevant nonmajor bleeding event; suspected minor bleeding events were not sent for adjudication.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixiban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Hemorrhagic anemia 20 15
Ecchymosis 5 9
Petechiae 2 2
Hemorrhage subcutaneous 1 0
Increased tendency to bruise 0 5
Vaginal hemorrhage 2 0
Menorrhagia 1 0
Uterine hemorrhage 0 1
Conjunctival hemorrhage 1 0
Hematoma infection 1 0
Spinal hematoma 0 1
9.Secondary Outcome
Title Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Hide Description Neurologic events were based on Medical Dictionary for Regulatory Activities search categories.For new or worsening events that were not related to the site of surgery, additional information was collected on a specific form. In addition, neurology consultation was to be obtained for these patients.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Paraesthesia 32 19
Hypoaesthesia 29 35
Burning sensation 7 5
Peroneal nerve palsy 5 6
Hypotonia 4 4
Dysarthria 3 1
Paresis 2 1
Cervicobrachial syndrome 1 1
Coordination abnormal 1 0
Hypertonia 1 1
Neuropathy peripheral 1 2
Peripheral nerve lesion 1 1
Radiculitis 1 0
Paralysis 0 1
Muscular weakness 7 11
Nerve injury 2 1
Femoral nerve injury 1 0
Sciatic nerve injury 1 0
Peroneal nerve injury 0 1
Diplopia 1 0
Gait disturbance 1 0
10.Secondary Outcome
Title Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Hide Description preRx=predose; LLN=lower limit of normal; ULN=upper limit of normal. MA criteria: Hemoglobin: >2 g/dL decrease from preRx or value ≤ 8 g/dL; hematocrit (%): <0.75*preRx; platelet count (*10^9 cells/L): <100,000/mm^3; erythrocytes (*10^6 cells/μL): <0.75*preRx level; leukocytes (*10^3 cells/μL): < 0.75*LLN or >1.25*ULN, or if preRx LLN use < 0.8*preRx or >ULN if preRx >ULN use >1.2*preRx or <LLN; basophils (*10^3 cells/μL): >400/mm^3; eosinophils (*10^3 cells/μL): > 0.75*10^3 cells/μL; lymphocytes (*10^3 cells/μL): >0.75*10^3 cells/μL; monocytes (*10^3 cells/μL): >2000/mm^3; neutrophils (*10^3 cells/μL): <1.0;
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Hemoglobin, low (n=2605, 2587) 2189 2218
Hematocrit, low (n=2554, 2536) 1274 1350
Platelet count, low (n=2597, 2576) 6 9
Erythrocytes, low (n=2558, 2540) 1310 1377
Leukocytes, low (n=2632, 2617) 54 54
Leukocytes, high (n=2632, 2617) 385 360
Basophils (absolute), high (n=2629, 2613) 1 3
Eosinophils (absolute), high (n=2629, 2613) 75 70
Lymphocytes (absolute), low (n=2629, 2613) 383 382
Lymphocytes (absolute), high (n=2629, 2613) 3 3
Monocytes (absolute), high (n=2629, 2613) 9 11
Neutrophils (absolute), low (n=2629, 2613) 5 4
11.Secondary Outcome
Title Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Hide Description preRx=predose; LLN=lower limit of normal; ULN=upper limit of normal. Alanine aminotransferase (ALT) (U/L): >3 *ULN: alkaline phosphatase (ALP) (U/L): >2* ULN; aspartate aminotransferase (ASP) (U/L): >3 *ULN; bilirubin, direct (mg/dL): >2*ULN; bilirubin, total (mg/dL): >2*ULN; BUN (mg/dL): >2*ULN; creatinine (mg/dL): >1.5*ULN; calcium (mg/dL): < 0.8*LLN or >1.2 *ULN, or if preRx <LLN use <0.75* preRx or >ULN if preRx >ULN use > 1.25*preRx or <LLN; chloride (mEq/L): <0.9*LLN or >1.1*ULN, or if preRx <LLN use <0.9*preRx or >ULN if preRx >ULN use >1.1* preRx or <LLN; bicarbonate (mEq/L): < 0.75* LLN or >1.25*ULN, or if preRx <LLN use <0.75*preRx or >ULN if preRx >ULN use >1.25*preRx or <LLN; potassium (mEq/L): < 0.9*LLN or >1.1*ULN, or if preRx <LLN use <0.9*preRx or >ULN if preRx >ULN use >1.1* preRx or < LLN; sodium (mEq/L): <0.95* LLN or >1.05×ULN, or if preRx <LLN use <0.95* predose or >ULN if preRx >ULN use >1.05 *preRx or < LLN.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Alkaline phosphatase, high (n=2631, 2618) 55 57
Alanine aminotransferase, high (n=2629, 2616) 50 83
Aspartate aminotransferase, high (n=2629, 2616) 73 73
Bilirubin, direct, high (n=2622, 2604) 145 139
Bilirubin, total, high (n=2630, 2617) 24 12
Blood urea nitrogen (BUN), high (n=2618, 2598) 19 17
Creatinine, high (n=2618, 2598) 21 25
Calcium, total, low (n=2618, 2598) 7 18
Calcium, total, high (n=2618, 2598) 0 1
Chloride, serum, low (n=2615, 2594) 6 6
Bicarbonate, low (n=2615, 2595) 8 8
Potassium, serum, low (n=2614, 2594) 73 73
Potassium, serum, high (n=2614, 2594) 61 47
Sodium, serum, low (n=2615, 2594) 29 23
Sodium, serum, high (n=2615, 2594) 5 4
12.Secondary Outcome
Title Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Hide Description preRx=predose; LLN=lower limit of normal; ULN=upper limit of normal. Glucose, fasting (mg/dL): <.8*LLN or >1.5*ULN, or if preRx <LLN use <.8*preRx or >ULN if preRx >ULN use >2*preRx or <LLN; protein, total (g/L): If missing preRx use ≥2, or if value ≥4 or preRx =0 or .5 use ≥2, or if preRx=1 use ≥3, or if preRx =2 or 3 use ≥4; creatine kinase (U/L): >5*ULN; uric acid (mg/dL): >.5* ULN, or if preRx >ULN use >2*preRx; blood, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx =2 or 3 use ≥4; glucose, urine : If missing preRx use ≥2, or if value ≥4, or if preRx=0 or .5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; RBC, urine (hpf): If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx dose= 1 use ≥3, or if preRx=2 or 3 use ≥4; WBC, urine (h): If missing preRx use ≥2, or if value ≥4, or if preRx =0 or .5 use ≥2, or if preRx =1 use ≥3, or if preRx=2 or 3 use ≥4.
Time Frame First dose of study drug (presurgery) through 2 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Glucose, fasting serum, high (n=14, 17) 0 1
Protein, total, low (n=2618, 2596) 747 752
Protein, total, high (n=2618, 2596) 3 1
Creatine kinase, high (n=2630, 2616) 615 642
Uric acid, high (n=2618, 2597) 2 3
Blood, urine, high (n=2588, 2568) 275 234
Glucose, urine, high (n=2588, 2568) 68 76
Leukocyte esterase, urine, high (n=21, 41) 0 4
Protein, urine (n=2588, 2568) 169 168
Red blood cells (RBC), urine, high (n=1310, 1230) 216 173
White blood cells (WBC),urine, high (n=1311, 1228) 217 229
13.Secondary Outcome
Title Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hide Description Treatment guidelines were provided for jaundice and elevated results of liver function tests.
Time Frame First dose of study drug (presurgery) through 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Unit of Measure: Participants
Aspartate aminotransferase increased 48 67
Alanine aminotransferase increased 40 61
Gamma-glutamyltransferase increased 27 54
Blood bilirubin increased 17 7
Bilirubin conjugated increased 11 12
Hepatic enzyme increased 9 16
Liver function test results abnormal 4 9
Transaminases increased 1 1
Cholelithiasis 2 0
Hepatitis toxic 2 0
Cholecystitis acute 1 0
Cholestasis 1 0
Hyperbilirubinemia 1 0
Postcholecystectomy syndrome 1 0
Cholecystitis 0 1
Hepatic pain 0 1
Hepatitis 0 1
Hepatomegaly 0 1
Jaundice cholestatic 0 1
Hypoalbuminemia 0 1
Hypoproteinemia 0 1
Yellow skin 0 1
14.Secondary Outcome
Title Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
Hide Description Event rate=Number of events divided by the number of patients evaluated. All suspected events were reported by investigator. Acute MI=the presence of a clinical situation (eg, abnormal history, physical examination, new electrocardiogram changes) suggestive of an MI and at least 1 of the following: elevated creatine kinase (CK)-MB or troponin T or troponin I ≥2*upper limit of normal (ULN); if CK-MB or troponin values not available, total CK ≥2*ULN; or new significant (≥0.04 sec) Q waves in ≥2 contiguous leads. Stroke=a new focal neurologic deficit of sudden onset lasting at least 24 hours that was not due to a readily identifiable nonvascular cause. Adjudication classified each reported stroke as primary hemorrhagic, nonhemorrhagic, infarction with hemorrhagic conversion, or unknown type. Thrombocytopenia=after 3 days as drop in platelet count to <100,000/mm^3 for patients with a baseline value >150,000/mm^3 or a >50% decline, if the baseline value was ≤150,000/mm^3.
Time Frame Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Apixaban, 2.5 mg BID Plus Placebo Enoxaparin, 40 mg QD Plus Placebo
Hide Arm/Group Description:
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Overall Number of Participants Analyzed 2673 2659
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of events/patients evaluated
MI/stroke
0.22
(0.09 to 0.51)
0.26
(0.12 to 0.56)
MI
0.19
(0.07 to 0.46)
0.11
(0.02 to 0.35)
Stroke
0.04
(0.00 to 0.24)
0.15
(0.05 to 0.41)
Thrombocytopenia
0.07
(0.00 to 0.30)
0.11
(0.02 to 0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.34 to 0.26
Estimation Comments Apixaban-enoxaparin. MI/stroke
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.17 to 0.34
Estimation Comments Apixaban-enoxaparin. MI
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.35 to 0.07
Estimation Comments Apixaban-enoxaparin. Stroke
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Apixaban, 2.5 mg BID Plus Placebo, Enoxaparin, 40 mg QD Plus Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.26 to 0.17
Estimation Comments Apixaban-enoxaparin. Thrombocytopenia
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Apixaban, 2.5 mg BID + Placebo Enoxaparin, 40 mg QD + Placebo
Hide Arm/Group Description Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD) Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
All-Cause Mortality
Apixaban, 2.5 mg BID + Placebo Enoxaparin, 40 mg QD + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Apixaban, 2.5 mg BID + Placebo Enoxaparin, 40 mg QD + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   184/2673 (6.88%)   172/2659 (6.47%) 
Blood and lymphatic system disorders     
Microcytic anaemia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Thrombocytopenia  1  0/2673 (0.00%)  3/2659 (0.11%) 
Anaemia  1  3/2673 (0.11%)  1/2659 (0.04%) 
Cardiac disorders     
Angina pectoris  1  1/2673 (0.04%)  0/2659 (0.00%) 
Angina unstable  1  1/2673 (0.04%)  0/2659 (0.00%) 
Acute coronary syndrome  1  1/2673 (0.04%)  0/2659 (0.00%) 
Tachycardia  1  3/2673 (0.11%)  1/2659 (0.04%) 
Cardiopulmonary failure  1  1/2673 (0.04%)  0/2659 (0.00%) 
Acute myocardial infarction  1  1/2673 (0.04%)  2/2659 (0.08%) 
Arrhythmia  1  0/2673 (0.00%)  1/2659 (0.04%) 
Atrial fibrillation  1  6/2673 (0.22%)  3/2659 (0.11%) 
Atrioventricular block second degree  1  1/2673 (0.04%)  0/2659 (0.00%) 
Cardiac arrest  1  1/2673 (0.04%)  0/2659 (0.00%) 
Bradycardia  1  0/2673 (0.00%)  1/2659 (0.04%) 
Myocardial infarction  1  5/2673 (0.19%)  1/2659 (0.04%) 
Ear and labyrinth disorders     
Vertigo  1  0/2673 (0.00%)  1/2659 (0.04%) 
Vertigo positional  1  0/2673 (0.00%)  1/2659 (0.04%) 
Gastrointestinal disorders     
Diverticulum intestinal haemorrhagic  1  1/2673 (0.04%)  0/2659 (0.00%) 
Haemorrhoids  1  1/2673 (0.04%)  1/2659 (0.04%) 
Pancreatitis  1  1/2673 (0.04%)  1/2659 (0.04%) 
Gastritis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Hiatus hernia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Abdominal compartment syndrome  1  1/2673 (0.04%)  0/2659 (0.00%) 
Abdominal pain  1  0/2673 (0.00%)  1/2659 (0.04%) 
Haematemesis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Ileus  1  4/2673 (0.15%)  2/2659 (0.08%) 
Constipation  1  2/2673 (0.07%)  0/2659 (0.00%) 
Gastrointestinal haemorrhage  1  1/2673 (0.04%)  0/2659 (0.00%) 
Intestinal obstruction  1  3/2673 (0.11%)  3/2659 (0.11%) 
Diarrhoea  1  1/2673 (0.04%)  0/2659 (0.00%) 
Duodenal ulcer  1  1/2673 (0.04%)  0/2659 (0.00%) 
Nausea  1  0/2673 (0.00%)  1/2659 (0.04%) 
Small intestinal obstruction  1  2/2673 (0.07%)  0/2659 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/2673 (0.04%)  0/2659 (0.00%) 
Mallory-Weiss syndrome  1  1/2673 (0.04%)  0/2659 (0.00%) 
Reflux oesophagitis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Ileal perforation  1  1/2673 (0.04%)  0/2659 (0.00%) 
General disorders     
Impaired healing  1  1/2673 (0.04%)  2/2659 (0.08%) 
Oedema  1  0/2673 (0.00%)  1/2659 (0.04%) 
Oedema peripheral  1  2/2673 (0.07%)  4/2659 (0.15%) 
Pyrexia  1  3/2673 (0.11%)  3/2659 (0.11%) 
Inflammation of wound  1  1/2673 (0.04%)  2/2659 (0.08%) 
Catheter site discharge  1  1/2673 (0.04%)  0/2659 (0.00%) 
Chest pain  1  0/2673 (0.00%)  1/2659 (0.04%) 
Hyperthermia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Secretion discharge  1  2/2673 (0.07%)  3/2659 (0.11%) 
Bloody discharge  1  1/2673 (0.04%)  0/2659 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Jaundice cholestatic  1  0/2673 (0.00%)  1/2659 (0.04%) 
Cholecystitis acute  1  1/2673 (0.04%)  0/2659 (0.00%) 
Cholecystitis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Immune system disorders     
Anaphylactic shock  1  0/2673 (0.00%)  2/2659 (0.08%) 
Contrast media allergy  1  2/2673 (0.07%)  0/2659 (0.00%) 
Anaphylactic reaction  1  1/2673 (0.04%)  0/2659 (0.00%) 
Infections and infestations     
Localised infection  1  2/2673 (0.07%)  0/2659 (0.00%) 
Cellulitis  1  0/2673 (0.00%)  3/2659 (0.11%) 
Lower respiratory tract infection  1  1/2673 (0.04%)  0/2659 (0.00%) 
Skin infection  1  1/2673 (0.04%)  0/2659 (0.00%) 
Subcutaneous abscess  1  0/2673 (0.00%)  2/2659 (0.08%) 
Wound infection  1  7/2673 (0.26%)  3/2659 (0.11%) 
Appendicitis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Pneumonia  1  2/2673 (0.07%)  3/2659 (0.11%) 
Upper respiratory tract infection  1  1/2673 (0.04%)  0/2659 (0.00%) 
Bronchitis  1  1/2673 (0.04%)  1/2659 (0.04%) 
Haematoma infection  1  1/2673 (0.04%)  0/2659 (0.00%) 
Postoperative wound infection  1  3/2673 (0.11%)  5/2659 (0.19%) 
Arthritis bacterial  1  1/2673 (0.04%)  0/2659 (0.00%) 
Osteomyelitis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Urinary tract infection  1  1/2673 (0.04%)  2/2659 (0.08%) 
Septic shock  1  1/2673 (0.04%)  0/2659 (0.00%) 
Device related infection  1  1/2673 (0.04%)  0/2659 (0.00%) 
Osteomyelitis chronic  1  1/2673 (0.04%)  0/2659 (0.00%) 
Post procedural infection  1  2/2673 (0.07%)  0/2659 (0.00%) 
Injury, poisoning and procedural complications     
Procedural pain  1  1/2673 (0.04%)  0/2659 (0.00%) 
Hip fracture  1  2/2673 (0.07%)  0/2659 (0.00%) 
Incorrect dose administered  1  0/2673 (0.00%)  1/2659 (0.04%) 
Lower limb fracture  1  0/2673 (0.00%)  1/2659 (0.04%) 
Multiple injuries  1  0/2673 (0.00%)  1/2659 (0.04%) 
Periprosthetic fracture  1  1/2673 (0.04%)  2/2659 (0.08%) 
Dislocation of joint prosthesis  1  5/2673 (0.19%)  11/2659 (0.41%) 
Fat embolism  1  0/2673 (0.00%)  1/2659 (0.04%) 
Seroma  1  1/2673 (0.04%)  0/2659 (0.00%) 
Wound secretion  1  5/2673 (0.19%)  3/2659 (0.11%) 
Arterial injury  1  0/2673 (0.00%)  1/2659 (0.04%) 
Fall  1  0/2673 (0.00%)  2/2659 (0.08%) 
Femur fracture  1  6/2673 (0.22%)  4/2659 (0.15%) 
Wound dehiscence  1  0/2673 (0.00%)  1/2659 (0.04%) 
Incision site haemorrhage  1  1/2673 (0.04%)  1/2659 (0.04%) 
Medical device complication  1  2/2673 (0.07%)  1/2659 (0.04%) 
Overdose  1  5/2673 (0.19%)  5/2659 (0.19%) 
Post procedural haematoma  1  2/2673 (0.07%)  0/2659 (0.00%) 
Post procedural haemorrhage  1  0/2673 (0.00%)  2/2659 (0.08%) 
Incision site haematoma  1  2/2673 (0.07%)  1/2659 (0.04%) 
Operative haemorrhage  1  4/2673 (0.15%)  1/2659 (0.04%) 
Anaemia postoperative  1  2/2673 (0.07%)  1/2659 (0.04%) 
Contrast media reaction  1  1/2673 (0.04%)  0/2659 (0.00%) 
Device dislocation  1  3/2673 (0.11%)  7/2659 (0.26%) 
Device failure  1  1/2673 (0.04%)  0/2659 (0.00%) 
Peroneal nerve injury  1  0/2673 (0.00%)  1/2659 (0.04%) 
Confusion postoperative  1  1/2673 (0.04%)  0/2659 (0.00%) 
Joint dislocation  1  8/2673 (0.30%)  7/2659 (0.26%) 
Post procedural discharge  1  1/2673 (0.04%)  3/2659 (0.11%) 
Postoperative wound complication  1  1/2673 (0.04%)  0/2659 (0.00%) 
Procedural site reaction  1  2/2673 (0.07%)  2/2659 (0.08%) 
Investigations     
Haemoglobin decreased  1  1/2673 (0.04%)  2/2659 (0.08%) 
White blood cell count increased  1  0/2673 (0.00%)  1/2659 (0.04%) 
Blood culture positive  1  1/2673 (0.04%)  0/2659 (0.00%) 
Blood creatinine increased  1  0/2673 (0.00%)  2/2659 (0.08%) 
Body temperature increased  1  2/2673 (0.07%)  1/2659 (0.04%) 
Drug level increased  1  1/2673 (0.04%)  0/2659 (0.00%) 
Haematocrit decreased  1  0/2673 (0.00%)  1/2659 (0.04%) 
Occult blood positive  1  1/2673 (0.04%)  0/2659 (0.00%) 
Oxygen saturation decreased  1  1/2673 (0.04%)  1/2659 (0.04%) 
C-reactive protein increased  1  0/2673 (0.00%)  1/2659 (0.04%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  1/2673 (0.04%)  1/2659 (0.04%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/2673 (0.00%)  2/2659 (0.08%) 
Exostosis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Osteochondrosis  1  0/2673 (0.00%)  2/2659 (0.08%) 
Unequal limb length  1  2/2673 (0.07%)  0/2659 (0.00%) 
Muscle spasms  1  1/2673 (0.04%)  0/2659 (0.00%) 
Pain in extremity  1  1/2673 (0.04%)  2/2659 (0.08%) 
Osteoarthritis  1  2/2673 (0.07%)  0/2659 (0.00%) 
Osteonecrosis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Mobility decreased  1  2/2673 (0.07%)  1/2659 (0.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Rectal cancer  1  1/2673 (0.04%)  0/2659 (0.00%) 
Chronic lymphocytic leukaemia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Metastases to liver  1  1/2673 (0.04%)  0/2659 (0.00%) 
Prostate cancer  1  1/2673 (0.04%)  0/2659 (0.00%) 
Colon neoplasm  1  1/2673 (0.04%)  0/2659 (0.00%) 
Nervous system disorders     
Hypoaesthesia  1  0/2673 (0.00%)  1/2659 (0.04%) 
Peroneal nerve palsy  1  2/2673 (0.07%)  0/2659 (0.00%) 
Cerebrovascular accident  1  1/2673 (0.04%)  4/2659 (0.15%) 
Dizziness  1  2/2673 (0.07%)  0/2659 (0.00%) 
Neuropathy peripheral  1  0/2673 (0.00%)  1/2659 (0.04%) 
Paralysis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Paresis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Monoparesis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Aphasia  1  0/2673 (0.00%)  1/2659 (0.04%) 
Cerebral infarction  1  0/2673 (0.00%)  1/2659 (0.04%) 
Sedation  1  1/2673 (0.04%)  2/2659 (0.08%) 
Sciatica  1  0/2673 (0.00%)  1/2659 (0.04%) 
Syncope  1  1/2673 (0.04%)  1/2659 (0.04%) 
Presyncope  1  0/2673 (0.00%)  1/2659 (0.04%) 
Transient ischaemic attack  1  0/2673 (0.00%)  1/2659 (0.04%) 
Psychiatric disorders     
Depression  1  1/2673 (0.04%)  0/2659 (0.00%) 
Mental status changes  1  0/2673 (0.00%)  1/2659 (0.04%) 
Alcohol withdrawal syndrome  1  1/2673 (0.04%)  0/2659 (0.00%) 
Suicidal ideation  1  0/2673 (0.00%)  1/2659 (0.04%) 
Suicide attempt  1  1/2673 (0.04%)  0/2659 (0.00%) 
Confusional state  1  2/2673 (0.07%)  0/2659 (0.00%) 
Renal and urinary disorders     
Haematuria  1  1/2673 (0.04%)  1/2659 (0.04%) 
Renal failure acute  1  3/2673 (0.11%)  0/2659 (0.00%) 
Renal failure chronic  1  0/2673 (0.00%)  1/2659 (0.04%) 
Urinary retention  1  0/2673 (0.00%)  1/2659 (0.04%) 
Renal artery stenosis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Reproductive system and breast disorders     
Prostatitis  1  0/2673 (0.00%)  1/2659 (0.04%) 
Breast hyperplasia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  1/2673 (0.04%)  0/2659 (0.00%) 
Lung disorder  1  1/2673 (0.04%)  0/2659 (0.00%) 
Hypoxia  1  0/2673 (0.00%)  1/2659 (0.04%) 
Pleurisy  1  0/2673 (0.00%)  1/2659 (0.04%) 
Pulmonary embolism  1  3/2673 (0.11%)  7/2659 (0.26%) 
Pleural effusion  1  0/2673 (0.00%)  1/2659 (0.04%) 
Atelectasis  1  1/2673 (0.04%)  1/2659 (0.04%) 
Dyspnoea  1  2/2673 (0.07%)  1/2659 (0.04%) 
Respiratory depression  1  1/2673 (0.04%)  0/2659 (0.00%) 
Skin and subcutaneous tissue disorders     
Ecchymosis  1  1/2673 (0.04%)  0/2659 (0.00%) 
Erythema  1  0/2673 (0.00%)  1/2659 (0.04%) 
Surgical and medical procedures     
Knee arthroplasty  1  1/2673 (0.04%)  0/2659 (0.00%) 
Vascular disorders     
Haematoma  1  4/2673 (0.15%)  2/2659 (0.08%) 
Deep vein thrombosis  1  8/2673 (0.30%)  18/2659 (0.68%) 
Wound haemorrhage  1  2/2673 (0.07%)  0/2659 (0.00%) 
Hypotension  1  6/2673 (0.22%)  4/2659 (0.15%) 
Ischaemia  1  1/2673 (0.04%)  0/2659 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Apixaban, 2.5 mg BID + Placebo Enoxaparin, 40 mg QD + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1260/2673 (47.14%)   1315/2659 (49.45%) 
Cardiac disorders     
Tachycardia  1  123/2673 (4.60%)  137/2659 (5.15%) 
Gastrointestinal disorders     
Constipation  1  318/2673 (11.90%)  364/2659 (13.69%) 
Nausea  1  485/2673 (18.14%)  529/2659 (19.89%) 
Vomiting  1  211/2673 (7.89%)  262/2659 (9.85%) 
General disorders     
Oedema peripheral  1  156/2673 (5.84%)  141/2659 (5.30%) 
Pyrexia  1  236/2673 (8.83%)  242/2659 (9.10%) 
Injury, poisoning and procedural complications     
Procedural pain  1  421/2673 (15.75%)  426/2659 (16.02%) 
Anaemia postoperative  1  163/2673 (6.10%)  156/2659 (5.87%) 
Nervous system disorders     
Dizziness  1  185/2673 (6.92%)  154/2659 (5.79%) 
Psychiatric disorders     
Insomnia  1  138/2673 (5.16%)  132/2659 (4.96%) 
Renal and urinary disorders     
Urinary retention  1  174/2673 (6.51%)  152/2659 (5.72%) 
Vascular disorders     
Hypotension  1  259/2673 (9.69%)  262/2659 (9.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00423319     History of Changes
Other Study ID Numbers: CV185-035
First Submitted: January 17, 2007
First Posted: January 18, 2007
Results First Submitted: April 14, 2014
Results First Posted: May 14, 2014
Last Update Posted: May 14, 2014