Trial Outcomes & Findings for Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3) (NCT NCT00423319)
NCT ID: NCT00423319
Last Updated: 2014-05-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
5407 participants
Primary outcome timeframe
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Results posted on
2014-05-14
Participant Flow
A total of 5765 subjects were enrolled, and 5407 were randomized to double-blind study drug.
Participant milestones
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Overall Study
STARTED
|
2708
|
2699
|
|
Overall Study
Participants Who Received Treatment
|
2673
|
2659
|
|
Overall Study
COMPLETED
|
2484
|
2447
|
|
Overall Study
NOT COMPLETED
|
224
|
252
|
Reasons for withdrawal
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Adverse Event
|
93
|
112
|
|
Overall Study
Withdrawal by Subject
|
86
|
99
|
|
Overall Study
Lost to Follow-up
|
4
|
3
|
|
Overall Study
Poor compliance or noncompliance
|
1
|
1
|
|
Overall Study
No longer meets study criteria
|
15
|
15
|
|
Overall Study
Other
|
23
|
22
|
Baseline Characteristics
Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
Baseline characteristics by cohort
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2708 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2699 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
Total
n=5407 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.9 Years
STANDARD_DEVIATION 11.79 • n=5 Participants
|
60.6 Years
STANDARD_DEVIATION 11.82 • n=7 Participants
|
60.8 Years
STANDARD_DEVIATION 11.81 • n=5 Participants
|
|
Age, Customized
Younger than 65 years
|
1608 Participants
n=5 Participants
|
1605 Participants
n=7 Participants
|
3213 Participants
n=5 Participants
|
|
Age, Customized
65 to younger than 75 years
|
770 Participants
n=5 Participants
|
767 Participants
n=7 Participants
|
1537 Participants
n=5 Participants
|
|
Age, Customized
75 years and older
|
330 Participants
n=5 Participants
|
327 Participants
n=7 Participants
|
657 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1430 Participants
n=5 Participants
|
1451 Participants
n=7 Participants
|
2881 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1278 Participants
n=5 Participants
|
1248 Participants
n=7 Participants
|
2526 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
450 Participants
n=5 Participants
|
441 Participants
n=7 Participants
|
891 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
32 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
217 Participants
n=5 Participants
|
219 Participants
n=7 Participants
|
436 Participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
274 Participants
n=5 Participants
|
276 Participants
n=7 Participants
|
550 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
57 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
77 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
155 Participants
n=5 Participants
|
|
Region of Enrollment
India
|
56 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
75 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
152 Participants
n=5 Participants
|
150 Participants
n=7 Participants
|
302 Participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
73 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
147 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
359 Participants
n=5 Participants
|
356 Participants
n=7 Participants
|
715 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
53 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
59 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
184 Participants
n=5 Participants
|
185 Participants
n=7 Participants
|
369 Participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
24 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
101 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
200 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
99 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
198 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
135 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
269 Participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
47 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
121 Participants
n=5 Participants
|
124 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
63 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
125 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dosePopulation: 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.
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=1949 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=1917 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
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
|
1.39 Percentage of events/patients evaluated
Interval 0.95 to 2.02
|
3.86 Percentage of events/patients evaluated
Interval 3.08 to 4.83
|
SECONDARY outcome
Timeframe: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dosePopulation: Randomized participants with either an adjudicated event or an adjudicated evaluable bilateral venogram
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2199 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2195 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
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
|
0.45 Percentage of events/patients evaluated
Interval 0.24 to 0.85
|
1.14 Percentage of events/patients evaluated
Interval 0.77 to 1.69
|
SECONDARY outcome
Timeframe: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dosePopulation: All participants randomized to treatment
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2708 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2699 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
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
Asymptomatic DVT (n=1943, 1907)
|
1.08 Percentage of events/patients evaluated
|
3.30 Percentage of events/patients evaluated
|
|
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
Symptomatic distal DVT
|
0.04 Percentage of events/patients evaluated
|
0.04 Percentage of events/patients evaluated
|
|
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
Asymptomatic distal DVT (n=1950, 1907)
|
0.97 Percentage of events/patients evaluated
|
2.94 Percentage of events/patients evaluated
|
|
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
All-cause death
|
0.11 Percentage of events/patients evaluated
|
0.04 Percentage of events/patients evaluated
|
|
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
VTE-related death
|
0.04 Percentage of events/patients evaluated
|
0.00 Percentage of events/patients evaluated
|
|
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
PE (fatal or nonfatal)
|
0.11 Percentage of events/patients evaluated
|
0.19 Percentage of events/patients evaluated
|
|
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
Nonfatal PE
|
0.07 Percentage of events/patients evaluated
|
0.19 Percentage of events/patients evaluated
|
|
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
All DVT (n=1944, 1911)
|
1.13 Percentage of events/patients evaluated
|
3.56 Percentage of events/patients evaluated
|
|
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
Symptomatic DVT
|
0.04 Percentage of events/patients evaluated
|
0.19 Percentage of events/patients evaluated
|
|
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
Proximal DVT (n=2196, 2190)
|
0.32 Percentage of events/patients evaluated
|
0.91 Percentage of events/patients evaluated
|
|
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
Distal DVT (1951, 1908)
|
1.03 Percentage of events/patients evaluated
|
2.99 Percentage of events/patients evaluated
|
|
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
Symptomatic proximal DVT
|
0.04 Percentage of events/patients evaluated
|
0.15 Percentage of events/patients evaluated
|
|
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
Asymptomatic proximal DVT (n=2195, 2187)
|
0.27 Percentage of events/patients evaluated
|
0.73 Percentage of events/patients evaluated
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
Major bleeding
|
0.82 Percentage of events/patients evaluted
Interval 0.54 to 1.25
|
0.68 Percentage of events/patients evaluted
Interval 0.42 to 1.08
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
CRNM
|
4.08 Percentage of events/patients evaluted
Interval 3.39 to 4.9
|
4.51 Percentage of events/patients evaluted
Interval 3.79 to 5.38
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
Major or CRNM
|
4.83 Percentage of events/patients evaluted
Interval 4.08 to 5.71
|
5.04 Percentage of events/patients evaluted
Interval 4.27 to 5.94
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
Any bleeding
|
11.71 Percentage of events/patients evaluted
Interval 10.55 to 12.99
|
12.56 Percentage of events/patients evaluted
Interval 11.36 to 13.88
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 30 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study medication
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
Death
|
2 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
SAEs
|
18 Participants
|
18 Participants
|
|
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
Bleeding AEs
|
15 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Postprocedural hemorrhagic
|
4 Participants
|
7 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hematuria traumatic
|
1 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Postprocedural hematoma
|
20 Participants
|
23 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Operative hemorrhage
|
19 Participants
|
14 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Incision site hematoma
|
14 Participants
|
10 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Incision site hemorrhage
|
13 Participants
|
19 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Periorbital hematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Subcutaneous hematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Traumatic hematoma
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hematoma
|
34 Participants
|
38 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Wound hemorrhage
|
18 Participants
|
15 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hemorrhage
|
13 Participants
|
13 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hematuria
|
41 Participants
|
39 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hemorrhage urinary tract
|
1 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Urethral hemorrhage
|
0 Participants
|
2 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Epistaxis
|
33 Participants
|
25 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Hemoptysis
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Hemorrhoidal hemorrhage
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Blood urine
|
1 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Occult blood positive
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Bloody discharge
|
16 Participants
|
13 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Catheter site hemorrhage
|
6 Participants
|
5 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Injection site hemorrhage
|
4 Participants
|
10 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Injection site hematoma
|
3 Participants
|
28 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Infusion site hematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Vessel puncture site hematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Hematocrit decreased
|
18 Participants
|
21 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Red blood cell count decreased
|
14 Participants
|
20 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Blood urine present
|
8 Participants
|
6 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Fibrin D dimer increased
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Hematochezia
|
6 Participants
|
2 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Mallory-Weiss Syndrome
|
4 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Hematemesis
|
3 Participants
|
2 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Melaena
|
3 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Rectal hemorrhage
|
3 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Gingival bleeding
|
2 Participants
|
3 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Anal hemorrhage
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Diarrhea hemorrhagic
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Diverticulum intestinal hemorrhagic
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Gastrointestinal hemorrhage
|
1 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Intra-abdominal hematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Duodenal ulcer hemorrhage
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Mouth hemorrhage
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Menorrhagia
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Spinal hematoma
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Ecchymosis
|
5 Participants
|
9 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Petechiae
|
2 Participants
|
2 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Hemorrhagic anemia
|
20 Participants
|
15 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Hemorrhage subcutaneous
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Increased tendency to bruise
|
0 Participants
|
5 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Vaginal hemorrhage
|
2 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Uterine hemorrhage
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Conjunctival hemorrhage
|
1 Participants
|
0 Participants
|
|
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Hematoma infection
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Femoral nerve injury
|
1 Participants
|
0 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Sciatic nerve injury
|
1 Participants
|
0 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Gait disturbance
|
1 Participants
|
0 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Paraesthesia
|
32 Participants
|
19 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Hypoaesthesia
|
29 Participants
|
35 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Burning sensation
|
7 Participants
|
5 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Peroneal nerve palsy
|
5 Participants
|
6 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Hypotonia
|
4 Participants
|
4 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Dysarthria
|
3 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Paresis
|
2 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Cervicobrachial syndrome
|
1 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Coordination abnormal
|
1 Participants
|
0 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Hypertonia
|
1 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Neuropathy peripheral
|
1 Participants
|
2 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Peripheral nerve lesion
|
1 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Radiculitis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Paralysis
|
0 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Muscular weakness
|
7 Participants
|
11 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Nerve injury
|
2 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Peroneal nerve injury
|
0 Participants
|
1 Participants
|
|
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Diplopia
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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;
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Hemoglobin, low (n=2605, 2587)
|
2189 Participants
|
2218 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Hematocrit, low (n=2554, 2536)
|
1274 Participants
|
1350 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Platelet count, low (n=2597, 2576)
|
6 Participants
|
9 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Erythrocytes, low (n=2558, 2540)
|
1310 Participants
|
1377 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Leukocytes, low (n=2632, 2617)
|
54 Participants
|
54 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Leukocytes, high (n=2632, 2617)
|
385 Participants
|
360 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Lymphocytes (absolute), low (n=2629, 2613)
|
383 Participants
|
382 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Monocytes (absolute), high (n=2629, 2613)
|
9 Participants
|
11 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Neutrophils (absolute), low (n=2629, 2613)
|
5 Participants
|
4 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Basophils (absolute), high (n=2629, 2613)
|
1 Participants
|
3 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Eosinophils (absolute), high (n=2629, 2613)
|
75 Participants
|
70 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Lymphocytes (absolute), high (n=2629, 2613)
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Alkaline phosphatase, high (n=2631, 2618)
|
55 Participants
|
57 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Alanine aminotransferase, high (n=2629, 2616)
|
50 Participants
|
83 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Bilirubin, direct, high (n=2622, 2604)
|
145 Participants
|
139 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Bilirubin, total, high (n=2630, 2617)
|
24 Participants
|
12 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Blood urea nitrogen (BUN), high (n=2618, 2598)
|
19 Participants
|
17 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Creatinine, high (n=2618, 2598)
|
21 Participants
|
25 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Calcium, total, low (n=2618, 2598)
|
7 Participants
|
18 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Calcium, total, high (n=2618, 2598)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Chloride, serum, low (n=2615, 2594)
|
6 Participants
|
6 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Bicarbonate, low (n=2615, 2595)
|
8 Participants
|
8 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Potassium, serum, low (n=2614, 2594)
|
73 Participants
|
73 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Potassium, serum, high (n=2614, 2594)
|
61 Participants
|
47 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Sodium, serum, low (n=2615, 2594)
|
29 Participants
|
23 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Sodium, serum, high (n=2615, 2594)
|
5 Participants
|
4 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Aspartate aminotransferase, high (n=2629, 2616)
|
73 Participants
|
73 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 2 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Glucose, fasting serum, high (n=14, 17)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Protein, total, low (n=2618, 2596)
|
747 Participants
|
752 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Protein, total, high (n=2618, 2596)
|
3 Participants
|
1 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Glucose, urine, high (n=2588, 2568)
|
68 Participants
|
76 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Protein, urine (n=2588, 2568)
|
169 Participants
|
168 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Creatine kinase, high (n=2630, 2616)
|
615 Participants
|
642 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Uric acid, high (n=2618, 2597)
|
2 Participants
|
3 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Blood, urine, high (n=2588, 2568)
|
275 Participants
|
234 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Leukocyte esterase, urine, high (n=21, 41)
|
0 Participants
|
4 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Red blood cells (RBC), urine, high (n=1310, 1230)
|
216 Participants
|
173 Participants
|
|
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
White blood cells (WBC),urine, high (n=1311, 1228)
|
217 Participants
|
229 Participants
|
SECONDARY outcome
Timeframe: First dose of study drug (presurgery) through 30 days after the last dose of study drugPopulation: All participants who received at least 1 dose of study drug
Treatment guidelines were provided for jaundice and elevated results of liver function tests.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hypoproteinemia
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Yellow skin
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Aspartate aminotransferase increased
|
48 Participants
|
67 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Alanine aminotransferase increased
|
40 Participants
|
61 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Gamma-glutamyltransferase increased
|
27 Participants
|
54 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Blood bilirubin increased
|
17 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Bilirubin conjugated increased
|
11 Participants
|
12 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hepatic enzyme increased
|
9 Participants
|
16 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Liver function test results abnormal
|
4 Participants
|
9 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Transaminases increased
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Cholelithiasis
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hepatitis toxic
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Cholecystitis acute
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Cholestasis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hyperbilirubinemia
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Postcholecystectomy syndrome
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Cholecystitis
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hepatic pain
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hepatitis
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hepatomegaly
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Jaundice cholestatic
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Hypoalbuminemia
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dosePopulation: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID Plus Placebo
n=2673 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=2659 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
MI/stroke
|
0.22 Percent of events/patients evaluated
Interval 0.09 to 0.51
|
0.26 Percent of events/patients evaluated
Interval 0.12 to 0.56
|
|
Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
MI
|
0.19 Percent of events/patients evaluated
Interval 0.07 to 0.46
|
0.11 Percent of events/patients evaluated
Interval 0.02 to 0.35
|
|
Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
Stroke
|
0.04 Percent of events/patients evaluated
Interval 0.0 to 0.24
|
0.15 Percent of events/patients evaluated
Interval 0.05 to 0.41
|
|
Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
Thrombocytopenia
|
0.07 Percent of events/patients evaluated
Interval 0.0 to 0.3
|
0.11 Percent of events/patients evaluated
Interval 0.02 to 0.35
|
Adverse Events
Apixaban, 2.5 mg BID + Placebo
Serious events: 184 serious events
Other events: 1260 other events
Deaths: 0 deaths
Enoxaparin, 40 mg QD + Placebo
Serious events: 172 serious events
Other events: 1315 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=2673 participants at risk
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=2659 participants at risk
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Cardiac disorders
Angina unstable
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Vascular disorders
Haematoma
|
0.15%
4/2673
|
0.08%
2/2659
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Localised infection
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Gastrointestinal disorders
Pancreatitis
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Cardiac disorders
Acute coronary syndrome
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Immune system disorders
Anaphylactic shock
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Infections and infestations
Cellulitis
|
0.00%
0/2673
|
0.11%
3/2659
|
|
Nervous system disorders
Cerebrovascular accident
|
0.04%
1/2673
|
0.15%
4/2659
|
|
Psychiatric disorders
Depression
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Dizziness
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Gastritis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Renal and urinary disorders
Haematuria
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.07%
2/2673
|
0.00%
0/2659
|
|
General disorders
Impaired healing
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Injury, poisoning and procedural complications
Incorrect dose administered
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Lower respiratory tract infection
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Periprosthetic fracture
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Infections and infestations
Skin infection
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Cardiac disorders
Tachycardia
|
0.11%
3/2673
|
0.04%
1/2659
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/2673
|
0.11%
3/2659
|
|
Gastrointestinal disorders
Abdominal compartment syndrome
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Vascular disorders
Deep vein thrombosis
|
0.30%
8/2673
|
0.68%
18/2659
|
|
Injury, poisoning and procedural complications
Dislocation of joint prosthesis
|
0.19%
5/2673
|
0.41%
11/2659
|
|
Injury, poisoning and procedural complications
Fat embolism
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Haematemesis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Investigations
Haemoglobin decreased
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Ileus
|
0.15%
4/2673
|
0.08%
2/2659
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.04%
1/2673
|
0.00%
0/2659
|
|
General disorders
Oedema
|
0.00%
0/2673
|
0.04%
1/2659
|
|
General disorders
Oedema peripheral
|
0.07%
2/2673
|
0.15%
4/2659
|
|
Nervous system disorders
Paralysis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Nervous system disorders
Paresis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.11%
3/2673
|
0.26%
7/2659
|
|
General disorders
Pyrexia
|
0.11%
3/2673
|
0.11%
3/2659
|
|
Renal and urinary disorders
Renal failure acute
|
0.11%
3/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Seroma
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Investigations
White blood cell count increased
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Wound infection
|
0.26%
7/2673
|
0.11%
3/2659
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.19%
5/2673
|
0.11%
3/2659
|
|
Cardiac disorders
Acute myocardial infarction
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Blood and lymphatic system disorders
Anaemia
|
0.11%
3/2673
|
0.04%
1/2659
|
|
Infections and infestations
Appendicitis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Arterial injury
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Investigations
Blood culture positive
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Constipation
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Immune system disorders
Contrast media allergy
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.22%
6/2673
|
0.15%
4/2659
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.04%
1/2673
|
0.04%
1/2659
|
|
General disorders
Inflammation of wound
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.11%
3/2673
|
0.11%
3/2659
|
|
Nervous system disorders
Monoparesis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Infections and infestations
Pneumonia
|
0.07%
2/2673
|
0.11%
3/2659
|
|
Psychiatric disorders
Suicide attempt
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Musculoskeletal and connective tissue disorders
Unequal limb length
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Infections and infestations
Upper respiratory tract infection
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Vascular disorders
Wound haemorrhage
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Aphasia
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Cardiac disorders
Atrial fibrillation
|
0.22%
6/2673
|
0.11%
3/2659
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Investigations
Blood creatinine increased
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Investigations
Body temperature increased
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Reproductive system and breast disorders
Breast hyperplasia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Infections and infestations
Bronchitis
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Cardiac disorders
Cardiac arrest
|
0.04%
1/2673
|
0.00%
0/2659
|
|
General disorders
Catheter site discharge
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/2673
|
0.04%
1/2659
|
|
General disorders
Chest pain
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Diarrhoea
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Investigations
Drug level increased
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Investigations
Haematocrit decreased
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Haematoma infection
|
0.04%
1/2673
|
0.00%
0/2659
|
|
General disorders
Hyperthermia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Vascular disorders
Hypotension
|
0.22%
6/2673
|
0.15%
4/2659
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Medical device complication
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Investigations
Occult blood positive
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Overdose
|
0.19%
5/2673
|
0.19%
5/2659
|
|
Investigations
Oxygen saturation decreased
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/2673
|
0.08%
2/2659
|
|
Infections and infestations
Postoperative wound infection
|
0.11%
3/2673
|
0.19%
5/2659
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Arthritis bacterial
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Incision site haematoma
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Operative haemorrhage
|
0.15%
4/2673
|
0.04%
1/2659
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.04%
1/2673
|
0.00%
0/2659
|
|
General disorders
Secretion discharge
|
0.07%
2/2673
|
0.11%
3/2659
|
|
Nervous system disorders
Sedation
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Urinary tract infection
|
0.04%
1/2673
|
0.08%
2/2659
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Contrast media reaction
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Device dislocation
|
0.11%
3/2673
|
0.26%
7/2659
|
|
Injury, poisoning and procedural complications
Device failure
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Vascular disorders
Ischaemia
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
0.07%
2/2673
|
0.04%
1/2659
|
|
Cardiac disorders
Myocardial infarction
|
0.19%
5/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Peroneal nerve injury
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory depression
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Sciatica
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Infections and infestations
Septic shock
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Syncope
|
0.04%
1/2673
|
0.04%
1/2659
|
|
Immune system disorders
Anaphylactic reaction
|
0.04%
1/2673
|
0.00%
0/2659
|
|
General disorders
Bloody discharge
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Investigations
C-reactive protein increased
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasm
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Confusion postoperative
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Psychiatric disorders
Confusional state
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Infections and infestations
Device related infection
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Gastrointestinal disorders
Ileal perforation
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.30%
8/2673
|
0.26%
7/2659
|
|
Infections and infestations
Osteomyelitis chronic
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Post procedural discharge
|
0.04%
1/2673
|
0.11%
3/2659
|
|
Infections and infestations
Post procedural infection
|
0.07%
2/2673
|
0.00%
0/2659
|
|
Injury, poisoning and procedural complications
Postoperative wound complication
|
0.04%
1/2673
|
0.00%
0/2659
|
|
Nervous system disorders
Presyncope
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.07%
2/2673
|
0.08%
2/2659
|
|
Renal and urinary disorders
Renal artery stenosis
|
0.00%
0/2673
|
0.04%
1/2659
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/2673
|
0.04%
1/2659
|
Other adverse events
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=2673 participants at risk
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=2659 participants at risk
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
15.8%
421/2673
|
16.0%
426/2659
|
|
Nervous system disorders
Dizziness
|
6.9%
185/2673
|
5.8%
154/2659
|
|
Psychiatric disorders
Insomnia
|
5.2%
138/2673
|
5.0%
132/2659
|
|
Cardiac disorders
Tachycardia
|
4.6%
123/2673
|
5.2%
137/2659
|
|
General disorders
Oedema peripheral
|
5.8%
156/2673
|
5.3%
141/2659
|
|
General disorders
Pyrexia
|
8.8%
236/2673
|
9.1%
242/2659
|
|
Gastrointestinal disorders
Constipation
|
11.9%
318/2673
|
13.7%
364/2659
|
|
Vascular disorders
Hypotension
|
9.7%
259/2673
|
9.9%
262/2659
|
|
Gastrointestinal disorders
Nausea
|
18.1%
485/2673
|
19.9%
529/2659
|
|
Renal and urinary disorders
Urinary retention
|
6.5%
174/2673
|
5.7%
152/2659
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
6.1%
163/2673
|
5.9%
156/2659
|
|
Gastrointestinal disorders
Vomiting
|
7.9%
211/2673
|
9.9%
262/2659
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER