Trial Outcomes & Findings for Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study) (NCT NCT01583218)

Last Updated: 2023-08-07

Results Overview

mITT Cohort 1: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, venous thromboembolism (VTE) related death adjudicated by a blinded independent Clinical Events Committee (CEC) between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

7513 participants

Primary outcome timeframe

mITT Cohort 1: Between randomization and Day 47 (max)

Results posted on

2023-08-07

Participant Flow

First patient was enrolled on 3/29/2012 and last patient completed the study on 1/15/2016. Patients meeting the inclusion and none of the exclusion criteria at screening were randomized 1:1 to either the betrixaban or enoxaparin treatment group.

To maintain the blind, patients either received betrixaban capsules for 35 to 42 days and daily subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days, or received daily SQ injections of enoxaparin for 10 ± 4 days and betrixaban placebo capsules for 35 to 42 days.

Participant milestones

Participant milestones
Measure	Betrixaban Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
Overall Study STARTED	3759	3754
Overall Study COMPLETED	3470	3471
Overall Study NOT COMPLETED	289	283

Reasons for withdrawal

Reasons for withdrawal
Measure	Betrixaban Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
Overall Study Withdrawal by Subject	43	29
Overall Study Death	206	211
Overall Study Lost to Follow-up	11	17
Overall Study Adverse event or serious adverse event	3	3
Overall Study Patient /Family decision	3	0
Overall Study Cannot contact patient directly	1	2
Overall Study SOURCE DOCUMENT/COORDINATOR MISSING	0	2
Overall Study Patient did not wish to attend visits	0	1
Overall Study Patient randomized but not dosed	17	16
Overall Study Patient was assessed via phone in person	1	0
Overall Study Patient deemed ineligible after random	2	0
Overall Study Patient was early terminated from study	0	1
Overall Study Patient was randomized due to mistake	1	0
Overall Study THE SUBJECT MOVED TO ANOTHER PROVINCE	0	1
Overall Study Withdraw of consent on day of random	1	0

Baseline Characteristics

Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Betrixaban n=3759 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3754 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days	Total n=7513 Participants Total of all reporting groups
Age, Continuous	76.6 years STANDARD_DEVIATION 8.46 • n=5 Participants	76.2 years STANDARD_DEVIATION 8.31 • n=7 Participants	76.4 years STANDARD_DEVIATION 8.39 • n=5 Participants
Age, Customized <75 years	1184 Participants n=5 Participants	1237 Participants n=7 Participants	2421 Participants n=5 Participants
Age, Customized >=75 years	2575 Participants n=5 Participants	2517 Participants n=7 Participants	5092 Participants n=5 Participants
Sex: Female, Male Female	2054 Participants n=5 Participants	2034 Participants n=7 Participants	4088 Participants n=5 Participants
Sex: Female, Male Male	1705 Participants n=5 Participants	1720 Participants n=7 Participants	3425 Participants n=5 Participants

PRIMARY outcome

Timeframe: mITT Cohort 1: Between randomization and Day 47 (max)

Population: Cohort 1 (participants with baseline D-dimer ≥ 2 x upper limit normal (ULN) as determined by the local lab) of the mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.

Outcome measures

Outcome measures
Measure	Betrixaban n=2314 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=2313 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
Modified Intent-to-Treat (mITT) Cohort 1: Percentage of Participants Experiencing the Composite Event of Symptomatic Deep Vein Thrombosis (DVT), Non-fatal Pulmonary Emboli (PE), VTE-related Death, or Asymptomatic Proximal DVT, Through Visit 3	5.70 Percentage of Participants Interval 4.76 to 6.65	7.18 Percentage of Participants Interval 6.12 to 8.23

PRIMARY outcome

Timeframe: mITT Cohort 2: Between randomization and Day 47 (max)

Population: Cohort 2 (encompasses "both" participants over 75 and participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab) of the mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.

mITT Cohort 2: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).

Outcome measures

Outcome measures
Measure	Betrixaban n=3407 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3391 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
mITT Cohort 2: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, VTE-related Death, or Asymptomatic Proximal DVT, Through Visit 3	4.70 Percentage of Participants Interval 3.99 to 5.41	6.02 Percentage of Participants Interval 5.22 to 6.82

PRIMARY outcome

Timeframe: mITT: Between randomization and Day 47 (max)

Population: The mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.

mITT: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).

Outcome measures

Outcome measures
Measure	Betrixaban n=3721 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3720 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
mITT: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, VTE-related Death, or Asymptomatic Proximal DVT, Through Visit 3	4.43 Percentage of Participants Interval 3.77 to 5.1	5.99 Percentage of Participants Interval 5.23 to 6.76

PRIMARY outcome

Timeframe: Between randomization and Day 49 (max)

Population: Safety population which consisted of all participants who had taken at least one dose of study drug.

Percentage of participants experiencing at least one major bleeding adjudicated by a blinded independent CEC between randomization (day 1) and up to seven days after discontinuation of all study medication.

Outcome measures

Outcome measures
Measure	Betrixaban n=3716 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3716 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
Percentage of Participants Experiencing Major Bleeding Through Seven Days After Discontinuation of All Study Medication	0.67 Percentage of Participants Interval 0.41 to 0.94	0.57 Percentage of Participants Interval 0.32 to 0.81

SECONDARY outcome

Timeframe: mITT Cohort 1: Between randomization and Day 42 (max)

Population: Cohort 1 (participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab) of the mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.

mITT Cohort 1: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).

Outcome measures

Outcome measures
Measure	Betrixaban n=2314 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=2313 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
mITT Cohort 1: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3	1.30 Percentage of Participants Interval 0.84 to 1.76	1.90 Percentage of Participants Interval 1.35 to 2.46

SECONDARY outcome

Timeframe: mITT Cohort 2: Between randomization and Day 42 (max)

mITT Cohort 2: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).

Outcome measures

Outcome measures
Measure	Betrixaban n=3407 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3391 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
mITT Cohort 2: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3	1.03 Percentage of Participants Interval 0.69 to 1.37	1.45 Percentage of Participants Interval 1.04 to 1.85

SECONDARY outcome

Timeframe: mITT: Between randomization and Day 42 (max)

mITT: Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).

Outcome measures

Outcome measures
Measure	Betrixaban n=3721 Participants Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3720 Participants Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
mITT: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3	0.94 Percentage of Participants Interval 0.63 to 1.25	1.45 Percentage of Participants Interval 1.07 to 1.84

Adverse Events

Betrixaban

Serious events: 657 serious events

Other events: 879 other events

Deaths: 0 deaths

Enoxaparin

Serious events: 615 serious events

Other events: 779 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Development

Portola Pharmaceuticals, Inc.

Phone: 650-246-7000

Results disclosure agreements

Principal investigator is a sponsor employee Due to multi centers, studies and countries this varies.
Publication restrictions are in place

Restriction type: OTHER

Measure	Betrixaban n=3716 participants at risk Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days	Enoxaparin n=3716 participants at risk Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
Infections and infestations Urinary tract infection	3.0% 110/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.1% 78/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Gastrointestinal disorders Constipation	2.9% 109/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.7% 102/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Metabolism and nutrition disorders Hypokalaemia	2.4% 91/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.3% 84/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Vascular disorders Hypertension	2.4% 88/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.2% 80/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Psychiatric disorders Insomnia	2.3% 87/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.4% 89/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Nervous system disorders Headache	2.0% 74/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.6% 59/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Gastrointestinal disorders Nausea	1.8% 67/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.5% 55/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Gastrointestinal disorders Diarrhoea	1.7% 63/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.6% 59/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Renal and urinary disorders Renal cyst	1.5% 55/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.3% 47/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.4% 53/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.1% 41/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Cardiac disorders Atrial fibrillation	1.3% 50/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	2.3% 85/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Cardiac disorders Cardiac failure	1.3% 48/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	0.86% 32/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 48/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	0.51% 19/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Renal and urinary disorders Haematuria	1.2% 46/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	0.62% 23/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Blood and lymphatic system disorders Anaemia	1.2% 44/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	0.78% 29/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Cardiac disorders Mitral valve incompetence	1.1% 41/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.3% 49/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
General disorders Oedema peripheral	1.0% 39/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	0.51% 19/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Cardiac disorders Tricuspid valve incompetence	1.0% 38/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.1% 41/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.
Vascular disorders Deep vein thrombosis	0.78% 29/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.	1.6% 58/3716 • From first dose date (including) till the end of study The number of patients at risk by study arm in the Adverse Events Results is based on Safety population, defined as patients who were randomized and received at least one dose of study drug. It leads to 3716 safety subjects in Betrixaban arm and 3716 in Enoxaprin arm which corresponds to the number of patients at risk in Adverse Events Results.