Trial Outcomes & Findings for Study of Apixaban for the Prevention of Thrombosis-related Events in Patients With Acute Medical Illness (NCT NCT00457002)

Last Updated: 2015-12-08

Results Overview

VTE: nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE could not be excluded as a cause. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

6758 participants

Primary outcome timeframe

Intended Treatment Period

Results posted on

2015-12-08

Participant Flow

First patient, first visit was June 2007 and last patient, last visit was May 2011. Acutely ill patients who had been hospitalized and had an expected hospitalization of an additional 3 or more days after randomization were enrolled.

6758 enrolled; 6528 randomized to treatment. Reasons for non-randomization: 2 Adverse event (AE); 34 withdrew consent; 1 death; 3 poor/non-compliance; 162 no longer met study criteria; 2 administrative reason by Sponsor; 26 other reasons.

Participant milestones

Participant milestones
Measure	Apixaban 2.5 mg Oral Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg Subcutaneous Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Overall Study STARTED	3255	3273
Overall Study COMPLETED	2442	2516
Overall Study NOT COMPLETED	813	757

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban 2.5 mg Oral Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg Subcutaneous Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Overall Study Death	40	47
Overall Study Adverse Event	284	260
Overall Study Withdrawal by Subject	299	271
Overall Study Lost to Follow-up	72	71
Overall Study Poor/Non-compliance	46	33
Overall Study No longer met criteria	41	37
Overall Study Administrative reason by Sponsor	1	0
Overall Study non-specified	29	38
Overall Study treated for 1 day; missing status/reason	1	0

Baseline Characteristics

Study of Apixaban for the Prevention of Thrombosis-related Events in Patients With Acute Medical Illness

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban 2.5 mg n=3255 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3273 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.	Total n=6528 Participants Total of all reporting groups
Age, Continuous	68.0 years n=5 Participants	67.0 years n=7 Participants	67.0 years n=5 Participants
Age, Customized Less than (<) 65 years	1401 participants n=5 Participants	1411 participants n=7 Participants	2812 participants n=5 Participants
Age, Customized Greater than, equal to (>=) 65 and < 75 years	890 participants n=5 Participants	884 participants n=7 Participants	1774 participants n=5 Participants
Age, Customized >= 75 years	964 participants n=5 Participants	978 participants n=7 Participants	1942 participants n=5 Participants
Sex: Female, Male Female	1629 Participants n=5 Participants	1696 Participants n=7 Participants	3325 Participants n=5 Participants
Sex: Female, Male Male	1626 Participants n=5 Participants	1577 Participants n=7 Participants	3203 Participants n=5 Participants
Region of Enrollment United States	625 participants n=5 Participants	620 participants n=7 Participants	1245 participants n=5 Participants
Region of Enrollment Philippines	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Region of Enrollment Hong Kong	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Region of Enrollment Taiwan	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Spain	51 participants n=5 Participants	50 participants n=7 Participants	101 participants n=5 Participants
Region of Enrollment Ukraine	270 participants n=5 Participants	276 participants n=7 Participants	546 participants n=5 Participants
Region of Enrollment Chile	65 participants n=5 Participants	65 participants n=7 Participants	130 participants n=5 Participants
Region of Enrollment Israel	168 participants n=5 Participants	168 participants n=7 Participants	336 participants n=5 Participants
Region of Enrollment Russian Federation	632 participants n=5 Participants	632 participants n=7 Participants	1264 participants n=5 Participants
Region of Enrollment Colombia	10 participants n=5 Participants	14 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Italy	35 participants n=5 Participants	34 participants n=7 Participants	69 participants n=5 Participants
Region of Enrollment India	198 participants n=5 Participants	202 participants n=7 Participants	400 participants n=5 Participants
Region of Enrollment France	203 participants n=5 Participants	200 participants n=7 Participants	403 participants n=5 Participants
Region of Enrollment Malaysia	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Denmark	49 participants n=5 Participants	54 participants n=7 Participants	103 participants n=5 Participants
Region of Enrollment Australia	51 participants n=5 Participants	49 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Peru	119 participants n=5 Participants	121 participants n=7 Participants	240 participants n=5 Participants
Region of Enrollment South Africa	52 participants n=5 Participants	48 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Korea, Republic of	33 participants n=5 Participants	33 participants n=7 Participants	66 participants n=5 Participants
Region of Enrollment Turkey	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Austria	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment United Kingdom	195 participants n=5 Participants	194 participants n=7 Participants	389 participants n=5 Participants
Region of Enrollment Hungary	18 participants n=5 Participants	16 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Czech Republic	53 participants n=5 Participants	56 participants n=7 Participants	109 participants n=5 Participants
Region of Enrollment Mexico	58 participants n=5 Participants	59 participants n=7 Participants	117 participants n=5 Participants
Region of Enrollment Canada	45 participants n=5 Participants	47 participants n=7 Participants	92 participants n=5 Participants
Region of Enrollment Argentina	78 participants n=5 Participants	77 participants n=7 Participants	155 participants n=5 Participants
Region of Enrollment Brazil	41 participants n=5 Participants	45 participants n=7 Participants	86 participants n=5 Participants
Region of Enrollment Belgium	21 participants n=5 Participants	22 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Poland	57 participants n=5 Participants	60 participants n=7 Participants	117 participants n=5 Participants
Region of Enrollment Singapore	8 participants n=5 Participants	12 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Norway	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Germany	35 participants n=5 Participants	32 participants n=7 Participants	67 participants n=5 Participants
Region of Enrollment Sweden	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Participants with Risk Factors Previous Venous Thromboembolism (VTE)	141 participants n=5 Participants	124 participants n=7 Participants	265 participants n=5 Participants
Participants with Risk Factors Estrogenic Hormone Therapy	49 participants n=5 Participants	27 participants n=7 Participants	76 participants n=5 Participants
Participants with Risk Factors History of Malignancy	312 participants n=5 Participants	320 participants n=7 Participants	632 participants n=5 Participants
Participants with Risk Factors Chronic Heart Failure	1531 participants n=5 Participants	1537 participants n=7 Participants	3068 participants n=5 Participants

PRIMARY outcome

Timeframe: Intended Treatment Period

Population: Those randomized (without suspected VTE) who had an adjudicated and evaluable ultrasound at end of intended treatment; or (with suspected VTE) had VTE events adjudicated as non-events and had an adjudicated and evaluable ultrasound at end of intended treatment, or had an adjudicated total VTE-related death.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2211 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2284 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population	2.71 Event rate (%) Interval 2.11 to 3.49	3.06 Event rate (%) Interval 2.43 to 3.86

PRIMARY outcome

Timeframe: Day 1, first dose of study drug, to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug were analyzed (As Treated population). Participants were categorized to the group to which they were randomized, unless the same incorrect treatment was received throughout the study; in such case, the As Treated were equal to the treatment received.

Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Major Bleeding During the Treatment Period in Treated Participants	0.47 Event Rate (%) Interval 0.28 to 0.79	0.19 Event Rate (%) Interval 0.08 to 0.42

PRIMARY outcome

Timeframe: Day 1, first dose of study drug, to last dose of study drug plus 2 days

Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants	2.26 Event Rate (%): Interval 1.8 to 2.84	1.90 Event Rate (%): Interval 1.48 to 2.43

PRIMARY outcome

Timeframe: Day 1, first dose of study drug, to last dose of study drug plus 2 days

Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants	2.67 Event Rate (%) Interval 2.16 to 3.29	2.08 Event Rate (%) Interval 1.64 to 2.64

PRIMARY outcome

Timeframe: Day 1, first dose of drug to last dose of drug plus 2 days

Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of All Bleeding During the Treatment Period in Treated Participants	7.73 Event Rate (%) Interval 6.85 to 8.71	6.81 Event Rate (%) Interval 5.99 to 7.73

SECONDARY outcome

Timeframe: Day 1 to last dose of parenteral study drug plus 1 day

Population: Those randomized (without suspected VTE) who had an adjudicated and evaluable ultrasound at end of parenteral treatment; or (with suspected VTE) had VTE events adjudicated as non-events and had adjudicated and evaluable ultrasound at end of parenteral treatment, or had an adjudicated VTE-related death during the Parenteral Treatment Period.

Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Key Secondary Efficacy population: all who received at least 1 dose of parenteral study drug and: (those without suspected VTE events during Parenteral Treatment) had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or (those with suspected VTE events during Parenteral Treatment) had those suspected VTE events adjudicated as non-events, and had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or had an adjudicated total VTE during Parenteral Treatment; or had an adjudicated VTE-related death during Parenteral Treatment. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2485 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2488 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants	1.73 Event rate (%) Interval 1.28 to 2.33	1.61 Event rate (%) Interval 1.18 to 2.19

SECONDARY outcome

Timeframe: Day 1 to last dose of parenteral study drug plus 1 day

Population: Secondary Efficacy Evaluable includes those who have an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event is not inadequate; or those with an adjudicated event that is part of the composite endpoint.

Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Secondary Efficacy Evaluable includes those who had an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event was not inadequate; or those with an adjudicated event that was part of the composite endpoint.. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2344 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2380 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants	1.66 Event Rate (%) Interval 1.22 to 2.28	1.51 Event Rate (%) Interval 1.09 to 2.1

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Those randomized with adjudicated and evaluable ultrasound at the end of the intended treatment period; for those with a suspected symptomatic event, the adjudication result was not inadequate; includes all those randomized who have an adjudicated event associated with the endpoint during Intended Treatment.

Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal (N-F) PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. All-Cause Death (A-C Death). Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2297 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2369 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period	6.44 Event Rate (%) Interval 5.51 to 7.53	6.63 Event Rate (%) Interval 5.69 to 7.71

SECONDARY outcome

Timeframe: Intended Treatment Period

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2297 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2368 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period	6.44 Event Rate (%) Interval 5.51 to 7.53	6.50 Event Rate (%) Interval 5.58 to 7.58

SECONDARY outcome

Timeframe: Intended Treatment Period

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2211 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2283 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period	2.71 Event Rate (%) Interval 2.11 to 3.49	2.93 Event Rate (%) Interval 2.32 to 3.72

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: All Randomized Participants.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3255 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3273 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants	0.06 Event Rate (%) Interval 0.0 to 0.24	0.09 Event Rate (%) Interval 0.02 to 0.29

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3251 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3269 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period	3.11 Event Rate (%) Interval 2.56 to 3.77	3.46 Event Rate (%) Interval 2.88 to 4.14

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.

Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3251 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3266 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period	0.40 Event Rate (%) Interval 0.23 to 0.69	0.80 Event Rate (%) Interval 0.54 to 1.17

SECONDARY outcome

Timeframe: Intended Treatment Period

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2304 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2371 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period	7.16 Event Rate (%) Interval 6.18 to 8.29	6.83 Event Rate (%) Interval 5.88 to 7.93

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3251 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3266 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated PE With Onset During the Intended Treatment Period	0.22 Event Rate (%) Interval 0.1 to 0.46	0.24 Event Rate (%) Interval 0.12 to 0.5

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3251 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3266 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period	0.22 Event Rate (%) Interval 0.1 to 0.46	0.24 Event Rate (%) Interval 0.12 to 0.5

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment were analyzed.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3255 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3273 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period	0.15 Event Rate (%) Interval 0.06 to 0.37	0.49 Event Rate (%) Interval 0.3 to 0.8

SECONDARY outcome

Timeframe: Intended Treatment Period

Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2207 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2276 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period	2.40 Event Rate (%) Interval 1.84 to 3.14	2.50 Event Rate (%) Interval 1.94 to 3.24

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants, except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment period, were analyzed.

Events were adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3255 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3273 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period	0.00 Event Rate (%) Interval 0.0 to 0.15	0.15 Event Rate (%) Interval 0.06 to 0.37

SECONDARY outcome

Timeframe: Intended Treatment Period

Population: Randomized participants, except those with an inadequate assessment for symptomatic events that are part of the endpoint during the intended treatment, were analyzed.

Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3255 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3273 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period	0.15 Event Rate (%) Interval 0.06 to 0.37	0.37 Event Rate (%) Interval 0.2 to 0.65

SECONDARY outcome

Timeframe: Intended Treatment Period

A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2206 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2269 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period	2.36 Event Rate (%) Interval 1.8 to 3.09	2.12 Event Rate (%) Interval 1.6 to 2.8

SECONDARY outcome

Timeframe: Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths)

Population: Participants who received at least one dose of study drug were analyzed (As Treated population).

Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for AEs, and 30 days after last dose of study drugs for SAEs and deaths.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants AEs	1871 participants	1910 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants SAEs	611 participants	601 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants Bleeding AEs	244 participants	221 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants Discontinuations Due to AE	290 participants	262 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants Deaths	131 participants	133 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.

Diastolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken with the participant either sitting, standing, or supine.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2227 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2301 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period Day of Discharge from Hospital (N=1607, 1625)	-1.0 mmHg Standard Deviation 12.69	-0.4 mmHg Standard Deviation 12.32
Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period Day 30 of Treatment + 2 (N=2227,2301)	0.0 mmHg Standard Deviation 12.91	-0.5 mmHg Standard Deviation 12.78

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.

Systolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken either sitting, standing, or supine.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2227 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2301 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period Discharge from Hospital (N=1607, 1625)	-3.0 mmHg Standard Deviation 19.12	-2.4 mmHg Standard Deviation 19.80
Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period Day 30 of Treatment + 2 (N=2227, 2301)	-2.3 mmHg Standard Deviation 19.79	-2.9 mmHg Standard Deviation 20.61

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a baseline value, and had a value on the day specified were analyzed.

Heart Rate was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Heart rate was measured in beats per minute (bpm) and could have been taken with participants either sitting, standing, or supine.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2225 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2299 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Mean Change From Baseline in Heart Rate in Treated Participants Hospital Discharge (N=1606,1622)	-5.4 bpm Standard Deviation 14.08	-5.1 bpm Standard Deviation 14.07
Mean Change From Baseline in Heart Rate in Treated Participants Day 30 of treatment (N=2225,2299)	-4.0 bpm Standard Deviation 15.62	-4.3 bpm Standard Deviation 14.83

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.

Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). Absolute (Abs). Hemoglobin: \>2 g/dL decrease compared to PreRx value or value \<=8 g/dL; Hematocrit: \<0.75\*PreRx; Erythrocytes: \<0.75\*PreRx c/µL; Leukocytes: \<0.75\*LLN or \> 1.25\*ULN, if PreRx \<LLN then use \<0.8\*PreRx or \>ULN, if PreRx \>ULN then use \>1.2\*PreRx or \< LLN; Platelet count: \< 100\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.75\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes \> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL or \> 7.5\*10\^3 c/ µL. Samples were obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2835 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2871 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Hemoglobin >2 g/dL decrease (N=2835, 2871)	133 participants	98 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Hematocrit <0.75*PreRx (N=2688, 2722)	23 participants	17 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Platelet Count < 100*10^9 c/L (N=2761, 2799)	9 participants	7 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Erythrocytes <0.75*PreRx c/µL (N=2697, 2730)	28 participants	16 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Leukocytes <0.75*LLN (N= 2835, 2869)	64 participants	55 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Leukocytes > 1.25*ULN (N=2835, 2869)	331 participants	283 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Abs Eosinophils > 0.75*10^3 c/µL (N=20, 24)	1 participants	1 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Abs Lymphocytes < 0.750103 c/ µL (N=20, 24)	4 participants	2 participants
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants Abs Monocytes > 2000/MM^3 (N= 19, 25)	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.

Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if PreRx \< LLN then use \< 0.75\* PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if PreRx \< LLN then use \< 0.75\*PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if PreRx \< LLN then use \< 0.95\*PreRx or \> ULN if PreRx \> ULN then use \> 1.05\*PreRx or \< LLN. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2862 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2893 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Calcium < 0.8*LLN (N=2861, 2893)	6 participants	8 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Calcium > 1.2*ULN (N=2861, 2893)	3 participants	3 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Chloride < 0.9*LLN (N=2861, 2886)	25 participants	25 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Chloride > 1.1*ULN (N=2861, 2886)	5 participants	1 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Bicarbonate < 0.75*LLN (N=2831, 2855)	5 participants	6 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Bicarbonate > 1.25*ULN (N=2831, 2855)	6 participants	4 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Potassium < 0.9*LLN (N=2851, 2878)	61 participants	58 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Potassium > 1.1*ULN (N=2851, 2878)	140 participants	137 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Sodium < 0.95*LLN (N=2862, 2888)	23 participants	25 participants
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants Sodium > 1.05*ULN (N=2862, 2888)	9 participants	6 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.

Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL \> 1.5\*ULN; Creatinine mg/dL: \> 1.5\*ULN; Alanine aminotransferase (ALT) U/L: \> 3\*ULN; Aspartate aminotransferase (AST) U/L: \> 3\*ULN; Alkaline phosphatase U/L: \> 2\*ULN; Bilirubin Direct mg/dL: \> 1.5\*ULN; Bilirubin Total mg/dL: \> 2\*ULN. Samples for laboratories obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2866 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2895 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants Alkaline phosphatase U/L > 2*ULN(N=2866, 2895)	35 participants	47 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants ALT U/L > 3*ULN (N=2827, 2861)	23 participants	33 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants AST U/L > 3*ULN (N=2831, 2863)	24 participants	29 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants Bilirubin Direct mg/dL > 1.5*ULN (N=2782, 2821)	123 participants	106 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants Bilirubin Total mg/dL > 2*ULN (N=2853, 2884)	17 participants	15 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants BUN mg/dL > 1.5*ULN (N=2864, 2891)	194 participants	188 participants
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants Creatinine mg/dL > 1.5*ULN (N=2862, 2892)	150 participants	156 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug, had a pre-therapy value, and had a value on the day specified were analyzed.

Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use 0.9\* PreRx or \> ULN if PreRx \> ULN then use 1.1 \*PreRx or \<LLN; Uric acid High: \> 1.5\* ULN, or if PreRx \> ULN then use \> 2 \*PreRx. Glucose Fasting: \<0.9\*LLN or \> 1.5\*ULN or if PreRx \< LLN then use \< 0.8\*PreRx or \> ULN, if PreRx \> ULN then use \>2.0\*PreRx. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) ± 2days.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2864 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2890 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Glucose Fasting <0.9*LLN (N=284,287)	5 participants	3 participants
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Glucose Fasting > 1.5*ULN (N=284,287)	39 participants	30 participants
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Total Protein < 0.9 *LLN (N=2864, 2890)	78 participants	51 participants
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Total Protein > 1.1*ULN (N=2864, 2890)	16 participants	8 participants
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Creatine kinase >5*ULN U/L(N=2856, 2888)	8 participants	10 participants
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants Uric acid > 1.5* ULN (N=2862, 2889)	47 participants	44 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: MI and thrombocytopenia categories: participants who received at least one dose of study drug. MI or stroke category: treated participants except those who did not have MI and had an inadequate assessment for stroke. Stroke category: treated participants except those with an inadequate assessment for stroke during the treatment period.

Events of Special Interest include: adjudicated thrombocytopenia, adjudicated myocardial infarction (MI), adjudicated stroke, and adjudicated MI or stroke. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants MI or stoke (N=3183, 3216)	0.38 Event Rate (%) Interval 0.21 to 0.67	0.37 Event Rate (%) Interval 0.21 to 0.66
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants MI (N=3184, 3217)	0.22 Event Rate (%) Interval 0.1 to 0.47	0.12 Event Rate (%) Interval 0.04 to 0.34
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants Stroke (N=3183, 3216)	0.16 Event Rate (%) Interval 0.06 to 0.38	0.25 Event Rate (%) Interval 0.12 to 0.5
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants Thrombocytopenia (N=3184, 3217)	0.19 Event Rate (%) Interval 0.08 to 0.42	0.09 Event Rate (%) Interval 0.02 to 0.29

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs)

Population: Participants who received at least one dose of study drug, and had available laboratory results associated with the event and treatment group.

Special interest include: liver function test increases, AEs related to liver function, and neurologic AEs. Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drug when summarizing AEs and through 30 days after the last dose when summarizing SAEs.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=3184 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=3217 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements Neurologic AEs	45 participants	42 participants
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements Neurologic SAEs	5 participants	1 participants
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements Liver-related AEs	127 participants	142 participants
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements Liver-related SAEs	9 participants	12 participants

SECONDARY outcome

Timeframe: Day 1 to last dose of study drug plus 2 days

Population: Participants who received at least one dose of study drug and had available laboratory measurements.

Liver function tests: Alanine aminotransferase (ALT) U/L; Aspartate aminotransferase (AST) U/L; Alkaline phosphatase U/L; Total Bilirubin (TBili) mg/dL. Elevations consist of \>3\*Upper Limit of Normal (ULN) for ALT and AST and elevation of \>2\*ULN for Bilirubin.

Outcome measures

Outcome measures
Measure	Apixaban 2.5 mg n=2853 Participants Oral administration of 2.5 mg apixaban tablets twice daily (BID) for 30 days plus placebo matching enoxaparin 40 mg QD while in hospital and for a minimum of 6 days.	Enoxaparin 40 mg n=2884 Participants Subcutaneous (SC) administration of 40 mg enoxaparin once daily (QD) for a minimum of 6 days plus placebo tablets matching apixaban 2.5 mg for 30 days.
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants ALT or AST >3ULN + TBili >2ULN (N=2818,2855)	2 participants	2 participants
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants AST Elevation >3*ULN (N=2831, 2863)	23 participants	28 participants
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants ALT Elevation >3*ULN (N=2827, 2861)	22 participants	32 participants
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants AST + ALT >3*ULN on same date (N= 2827, 2861)	14 participants	13 participants
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants TBili >2*ULN (N= 2853, 2884)	13 participants	14 participants
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants ALT>3ULN + TBili >2ULN (N=2817, 2853)	0 participants	2 participants

Adverse Events

Apix 2.5mg BID

Serious events: 611 serious events

Other events: 0 other events

Deaths: 0 deaths

Enox 40mg QD

Serious events: 601 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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