Trial Outcomes & Findings for Study of Apixaban for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery (NCT NCT00371683)

Last Updated: 2015-12-30

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3608 participants

Primary outcome timeframe

From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Results posted on

2015-12-30

Participant Flow

3608 patients enrolled and 3195 were randomized to double blind (DB) Treatment Period: 413 not randomized due to: 227 no longer met criteria, 109 withdrew consent, 60 other reasons, 11 administrative reason by sponsor, 5 adverse event, 1 poor, non-compliance.

Participant milestones

Participant milestones
Measure	Apixaban 2.5mg BID Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug (day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).	Enoxaparin 30 mg SC Injection q 12 Hours Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug(day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).
DB Treatment Period-Randomized Patients STARTED	1599	1596
DB Treatment Period-Randomized Patients COMPLETED	1509	1489
DB Treatment Period-Randomized Patients NOT COMPLETED	90	107
Follow-Up Period - Randomized Patients STARTED	1553	1533
Follow-Up Period - Randomized Patients COMPLETED	1492	1461
Follow-Up Period - Randomized Patients NOT COMPLETED	61	72

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban 2.5mg BID Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug (day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).	Enoxaparin 30 mg SC Injection q 12 Hours Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug(day of surgery or next day); and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).
DB Treatment Period-Randomized Patients Death	1	1
DB Treatment Period-Randomized Patients Adverse Event	60	58
DB Treatment Period-Randomized Patients Withdrawal by Subject	18	37
DB Treatment Period-Randomized Patients Lost to Follow-up	0	1
DB Treatment Period-Randomized Patients No longer meets study criteria	1	2
DB Treatment Period-Randomized Patients Administrative reason by sponsor	1	0
DB Treatment Period-Randomized Patients non-specified	9	8
Follow-Up Period - Randomized Patients Withdrawal by Subject	17	19
Follow-Up Period - Randomized Patients Death	0	2
Follow-Up Period - Randomized Patients Lost to Follow-up	38	39
Follow-Up Period - Randomized Patients non-specified	6	12

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).	Total n=3195 Participants Total of all reporting groups
Age, Continuous	65.9 years STANDARD_DEVIATION 9.26 • n=5 Participants	65.7 years STANDARD_DEVIATION 9.22 • n=7 Participants	65.8 years STANDARD_DEVIATION 9.24 • n=5 Participants
Age, Customized Less than(<) 65 years	697 participants n=5 Participants	691 participants n=7 Participants	1388 participants n=5 Participants
Age, Customized Greater than, equal to (>=) 65 and < 75 years	593 participants n=5 Participants	610 participants n=7 Participants	1203 participants n=5 Participants
Age, Customized >=75 years	309 participants n=5 Participants	295 participants n=7 Participants	604 participants n=5 Participants
Sex: Female, Male Female	997 Participants n=5 Participants	986 Participants n=7 Participants	1983 Participants n=5 Participants
Sex: Female, Male Male	602 Participants n=5 Participants	610 Participants n=7 Participants	1212 Participants n=5 Participants
Region of Enrollment Argentina	43 participants n=5 Participants	43 participants n=7 Participants	86 participants n=5 Participants
Region of Enrollment Russian Federation	15 participants n=5 Participants	13 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Hungary	28 participants n=5 Participants	26 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment United States	464 participants n=5 Participants	474 participants n=7 Participants	938 participants n=5 Participants
Region of Enrollment Canada	554 participants n=5 Participants	548 participants n=7 Participants	1102 participants n=5 Participants
Region of Enrollment Sweden	66 participants n=5 Participants	68 participants n=7 Participants	134 participants n=5 Participants
Region of Enrollment Turkey	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Denmark	87 participants n=5 Participants	89 participants n=7 Participants	176 participants n=5 Participants
Region of Enrollment Brazil	42 participants n=5 Participants	39 participants n=7 Participants	81 participants n=5 Participants
Region of Enrollment Poland	35 participants n=5 Participants	35 participants n=7 Participants	70 participants n=5 Participants
Region of Enrollment Mexico	138 participants n=5 Participants	138 participants n=7 Participants	276 participants n=5 Participants
Region of Enrollment Israel	44 participants n=5 Participants	42 participants n=7 Participants	86 participants n=5 Participants
Region of Enrollment Australia	50 participants n=5 Participants	54 participants n=7 Participants	104 participants n=5 Participants
Region of Enrollment Norway	21 participants n=5 Participants	17 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Primary Population=All randomized participants who: have an adjudicated and evaluable bilateral venogram performed during the Intended Treatment Period; or have an adjudicated VTE during the Intended Treatment Period; or die due to any cause during the Intended Treatment Period.

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1157 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1130 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects	8.99 percentage of participants Interval 7.47 to 10.79	8.85 percentage of participants Interval 7.33 to 10.66

PRIMARY outcome

Timeframe: First dose of study drug to last dose, plus 2 days post last dose

Population: All participants who received at least one dose of study drug (Treated population).

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1596 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1588 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population Major Bleeding (n=1596, 1588)	0.69 percentage of participants Interval 0.37 to 1.25	1.39 percentage of participants Interval 0.91 to 2.11
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population CR N-M Bleeding (n=1596, 1588)	2.19 percentage of participants Interval 1.58 to 3.05	2.96 percentage of participants Interval 2.23 to 3.93
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population Major or CR N-M Bleeding(n=1596, 1588)	2.88 percentage of participants Interval 2.16 to 3.84	4.28 percentage of participants Interval 3.39 to 5.41
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population Any Bleeding (n=1596, 1588)	5.33 percentage of participants Interval 4.33 to 6.55	6.80 percentage of participants Interval 5.66 to 8.16

PRIMARY outcome

Timeframe: Last dose of study drug to Day 72 (60 days)

Population: All participants who received at least 1 dose of study drug during the Treatment Period and entered the Follow-Up Period.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1563 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1553 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period Major Bleeding (n=1563, 1553)	0.13 percentage of participants Interval 0.01 to 0.51	0.13 percentage of participants Interval 0.01 to 0.51
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period CR N-M Bleeding (n=1563, 1553)	0.26 percentage of participants Interval 0.08 to 0.69	0.45 percentage of participants Interval 0.2 to 0.96
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period Major or CR N-M Bleeding (n=1563, 1553)	0.38 percentage of participants Interval 0.16 to 0.86	0.58 percentage of participants Interval 0.29 to 1.12
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period Any Bleeding (n=1563, 1553)	0.90 percentage of participants Interval 0.52 to 1.52	1.29 percentage of participants Interval 0.83 to 2.0

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated non-fatal PE or death, during the Intended Treatment Period, were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1269 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1216 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period	2.05 percentage of participants Interval 1.39 to 3.01	1.64 percentage of participants Interval 1.06 to 2.55

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1156 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1127 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period	8.91 percentage of participants Interval 7.4 to 10.71	8.61 percentage of participants Interval 7.1 to 10.4

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1268 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1213 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period	1.97 percentage of participants Interval 1.33 to 2.92	1.40 percentage of participants Interval 0.86 to 2.26

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1270 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1219 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period	2.13 percentage of participants Interval 1.46 to 3.1	1.97 percentage of participants Interval 1.32 to 2.94

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1269 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1216 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period	2.05 percentage of participants Interval 1.39 to 3.01	1.73 percentage of participants Interval 1.12 to 2.65

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: All Randomized participants were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With All-Cause Death During the Intended Treatment Period	0.19 percentage of participants Interval 0.04 to 0.59	0.19 percentage of participants Interval 0.04 to 0.59

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: All randomized participants were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period	0.13 percentage of participants Interval 0.0 to 0.49	0.00 percentage of participants Interval 0.0 to 0.3

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: All randomized participants were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period	1.25 percentage of participants Interval 0.8 to 1.94	1.00 percentage of participants Interval 0.61 to 1.64

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: All randomized participants were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period	1.19 percentage of participants Interval 0.75 to 1.87	0.81 percentage of participants Interval 0.46 to 1.41

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Randomized participants with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint, during the Intended Treatment Period, were analyzed.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1162 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1141 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period	9.90 percentage of participants Interval 8.31 to 11.76	10.60 percentage of participants Interval 8.95 to 12.54

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: All randomized participants: PE, Symptomatic DVT, Symptomatic Proximal DVT, Symptomatic Distal DVT. Randomized with an adjudicated and evaluable bilateral venogram or an adjudicated event associated with the endpoint: All DVT, Asymptomatic DVT. n=number analyzed in each category

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1599 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1596 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period PE (Fatal or Non-Fatal) (n=1599, 1596)	1.00 percentage of participants Interval 0.61 to 1.64	0.44 percentage of participants Interval 0.2 to 0.93
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period Non-Fatal PE (n=1599, 1596)	0.88 percentage of participants Interval 0.51 to 1.49	0.44 percentage of participants Interval 0.2 to 0.93
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period All DVT n=1142, 1122	7.79 percentage of participants Interval 6.37 to 9.51	8.20 percentage of participants Interval 6.73 to 9.97
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period Symptomatic DVT (n=1599, 1596)	0.19 percentage of participants Interval 0.04 to 0.59	0.44 percentage of participants Interval 0.2 to 0.93
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period Asymptomatic DVT (n=1139,1115)	7.55 percentage of participants Interval 6.15 to 9.25	7.62 percentage of participants Interval 6.2 to 9.35
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period Symptomatic Proximal DVT (n=1599,1596)	0.13 percentage of participants Interval 0.0 to 0.49	0.19 percentage of participants Interval 0.04 to 0.59
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period Symptomatic Distal DVT (n=1599,1596)	0.06 percentage of participants Interval 0.0 to 0.4	0.38 percentage of participants Interval 0.15 to 0.85

SECONDARY outcome

Timeframe: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization

Population: Randomized participants with either an adjudicated and evaluable bilateral proximal (or distal, as appropriate) venogram or an adjudicated event associated with the endpoint. n= number analyzed

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1254 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1207 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period Proximal DVT (n=1254, 1207)	0.72 percentage of participants Interval 0.36 to 1.39	0.91 percentage of participants Interval 0.49 to 1.65
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period Distal DVT (n=1146, 1133)	7.24 percentage of participants Interval 5.88 to 8.91	8.03 percentage of participants Interval 6.58 to 9.78
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period Asymptomatic Distal DVT (n=1145, 1127)	7.16 percentage of participants Interval 5.8 to 8.82	7.54 percentage of participants Interval 6.14 to 9.25
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period Asymptomatic Proximal DVT (n=1252, 1204)	0.56 percentage of participants Interval 0.25 to 1.18	0.66 percentage of participants Interval 0.32 to 1.34

SECONDARY outcome

Timeframe: From first dose to last dose, plus 2 days (12 days, plus 2)

Population: All participants who received at least one dose of study drug were analyzed (Treated Population).

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1596 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1588 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period MI/Stroke	0.06 percentage of participants Interval 0.0 to 0.4	0.31 percentage of participants Interval 0.11 to 0.77
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period MI	0.06 percentage of participants Interval 0.0 to 0.4	0.25 percentage of participants Interval 0.08 to 0.68
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period Stroke	0.00 percentage of participants Interval 0.0 to 0.3	0.13 percentage of participants Interval 0.01 to 0.5
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period Thrombocytopenia	0.00 percentage of participants Interval 0.0 to 0.3	0.13 percentage of participants Interval 0.01 to 0.5

SECONDARY outcome

Timeframe: Post last dose of study drug to Day 72 (60 days)

Population: Participants who received at least one dose of study drug and entered the Follow-Up period

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1563 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1553 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period MI/Stroke	0.06 percentage of participants Interval 0.0 to 0.41	0.06 percentage of participants Interval 0.0 to 0.41
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period MI	0.06 percentage of participants Interval 0.0 to 0.41	0.06 percentage of participants Interval 0.0 to 0.41
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period Stroke	0.00 percentage of participants Interval 0.0 to 0.3	0.00 percentage of participants Interval 0.0 to 0.31
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period Thrombocytopenia	0.00 percentage of participants Interval 0.0 to 0.3	0.00 percentage of participants Interval 0.0 to 0.31

SECONDARY outcome

Timeframe: First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)

Population: All participants who received at least 1 dose of study drug during the Treatment Period.

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.

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1596 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1588 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population SAE	123 participants	123 participants
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population Bleeding AE	110 participants	144 participants
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population AEs leading to discontinuation	60 participants	58 participants
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population Deaths	3 participants	5 participants

SECONDARY outcome

Timeframe: Baseline to last dose of study drug, plus 2 days

Population: All participants who received at least one dose of study drug and had blood pressure measurements at baseline were summarized.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1577 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1574 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Systolic BP Day 12 (n=1495,1463)	9.1 mmHg Standard Error 0.543	8.9 mmHg Standard Error 0.562
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Diastolic BP Day 1 (n=240, 237)	-0.4 mmHg Standard Error 0.741	-0.9 mmHg Standard Error 0.738
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Diastolic BP Day 2 (n=1577, 1574)	1.7 mmHg Standard Error 0.301	1.5 mmHg Standard Error 0.305
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Diastolic BP Day 3 (n=1489,1498)	2.3 mmHg Standard Error 0.322	2.1 mmHg Standard Error 0.321
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Diastolic BP Day 4 (n=127,134)	0.6 mmHg Standard Error 1.217	0.3 mmHg Standard Error 1.104
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Diastolic BP Day 12 (n=1495,1463)	7.3 mmHg Standard Error 0.342	7.5 mmHg Standard Error 0.343
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Systolic BP Day 1 (n=240,237)	1.5 mmHg Standard Error 1.189	-0.7 mmHg Standard Error 1.303
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Systolic BP Day 2 (n=1577,1574)	5.4 mmHg Standard Error 0.505	4.2 mmHg Standard Error 0.518
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Systolic BP Day 3 (n=1489,1498)	4.7 mmHg Standard Error 0.536	4.3 mmHg Standard Error 0.555
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period Systolic BP Day 4 (n=127,134)	2.8 mmHg Standard Error 2.129	1.4 mmHg Standard Error 1.871

SECONDARY outcome

Timeframe: Baseline to last dose of study drug, plus 2 days

Population: All participants who received at least one dose of study drug and had heart rate measurements at baseline were summarized.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1575 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1574 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Mean Change From Baseline in Heart Rate During the Treatment Period Heart Rate Day 1 (n=240,237)	2.3 bpm Standard Error 0.761	2.7 bpm Standard Error 0.761
Mean Change From Baseline in Heart Rate During the Treatment Period Heart Rate Day 2 (n=1575,1574)	4.6 bpm Standard Error 0.312	4.5 bpm Standard Error 0.317
Mean Change From Baseline in Heart Rate During the Treatment Period Heart Rate Day 3 (n=1490,1498)	4.5 bpm Standard Error 0.334	5.0 bpm Standard Error 0.344
Mean Change From Baseline in Heart Rate During the Treatment Period Heart Rate Day 4 (n=127,134)	7.6 bpm Standard Error 1.365	9.4 bpm Standard Error 1.320
Mean Change From Baseline in Heart Rate During the Treatment Period Heart Rate Day 12 (n=1495, 1462)	-0.3 bpm Standard Error 0.361	-0.1 bpm Standard Error 0.375

SECONDARY outcome

Timeframe: First dose to last dose of study drug (12 days), plus 2 days

Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1583 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1572 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Hemoglobin low (n=1561,1549)	386 participants	392 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Hematocrit low (n=1558,1547)	135 participants	157 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Platelet count low (n=1556,1543)	6 participants	9 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Erythrocytes low (n=1557,1547)	130 participants	149 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Leukocytes low(n=1583,1572)	8 participants	11 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Leukocytes high(n=1583,1572)	214 participants	210 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Basophils high (n=1577, 1564)	0 participants	2 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Eosinophils high (n=1577, 1564)	32 participants	13 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Lymphocytes low (n=1577,1564)	125 participants	117 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Lymphocytes high (n=1577,1564)	2 participants	4 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Monocytes high (n=1577,1564)	4 participants	4 participants
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period Neutrophils low (n=1577,1564)	4 participants	5 participants

SECONDARY outcome

Timeframe: First dose to last dose of study drug (12 days), plus 2 days

Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1573 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1563 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period ALP high (n=1573,1563)	42 participants	55 participants
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period ALT high (n=1573,1562)	33 participants	45 participants
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period AST high (n=1573,1562)	29 participants	40 participants
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period Bilirubin direct high (n=1563,1553)	63 participants	54 participants
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period Bilirubin total high(n=1572,1562)	2 participants	8 participants
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period Creatinine high (n=1569,1562)	17 participants	28 participants

SECONDARY outcome

Timeframe: First dose to last dose of study drug (12 days), plus 2 days

Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1569 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1562 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Calcium low (n=1569,1562)	1 participants	5 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Calcium high (n=1569,1562)	0 participants	1 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Chloride low (n=1568,1562)	11 participants	17 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Chloride high (n=1568,1562)	0 participants	1 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Bicarbonate low (n=1568,1561)	11 participants	13 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Potassium low(n=1568,1559)	54 participants	56 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Potassium high(n=1568,1559)	26 participants	20 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Sodium low (n=1568,1562)	23 participants	39 participants
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period Sodium high (n=1568,1562)	2 participants	0 participants

SECONDARY outcome

Timeframe: First dose to last dose of study drug (12 days), plus 2 days

Population: All participants who received at least one dose of study drug and had available laboratory results for that analyte and treatment group.

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

Outcome measures

Outcome measures
Measure	Apixaban 2.5mg BID n=1573 Participants Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, ± 2 days.	Enoxaparin 30 mg SC Injection q 12 Hours n=1563 Participants Enoxaparin 30 mg SC injection q 12 h plus matching placebo tablets BID for 12 days, ± 2 days.
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period Fasting Glucose low (n=611, 579)	8 participants	5 participants
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period Fasting Glucose high (n=611, 579)	54 participants	28 participants
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period Total Protein low (n=1568,1562)	527 participants	513 participants
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period CK high (n=1573,1563)	52 participants	45 participants
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period Uric Acid high (n=1567,1562)	22 participants	12 participants

Adverse Events

Apixaban 2.5mg BID

Serious events: 123 serious events

Other events: 713 other events

Deaths: 0 deaths

Enoxaparin 30 mg SC Injection q 12 Hours

Serious events: 123 serious events

Other events: 741 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Apixaban 2.5mg BID n=1596 participants at risk Apixaban 2.5 mg tablets twice a day (BID) plus matching placebo SC injection q 12 hours for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).	Enoxaparin 30 mg SC Injection q 12 Hours n=1588 participants at risk Enoxaparin 30 mg subcutaneous (SC) injection every (q) 12 hours (h) plus matching placebo tablets BID for 12 days, plus or minus 2 days. The study included a screening period that began no more than 30 days prior to surgery through 24 hours after surgery; a 12 (±2) day treatment period, starting on the day of the first dose of study drug; and a 60 (±3) day follow-up period, starting the day after the last dose of study drug (End of Treatment Period to Day 72).
Gastrointestinal disorders Vomiting	6.2% 99/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	6.4% 102/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Psychiatric disorders Insomnia	4.8% 77/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	5.4% 86/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Nervous system disorders Dizziness	6.5% 103/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	5.5% 88/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Vascular disorders Deep vein thrombosis	8.0% 127/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	7.1% 113/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Gastrointestinal disorders Nausea	13.0% 208/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	15.2% 241/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Gastrointestinal disorders Constipation	14.2% 227/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	14.7% 234/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
General disorders Oedema peripheral	8.2% 131/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	9.6% 153/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 84/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	4.8% 77/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.
General disorders Pyrexia	8.6% 137/1596 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.	9.4% 149/1588 • First dose to last dose, plus 2 days for AEs or plus 30 days for SAEs. All participants who received at least one dose of study drug were included.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

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