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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether extended prophylaxis with oral betrixaban can prevent blood clots in the leg and lung that sometime occur in patients hospitalized for an acute medical illness and to compare these results with standard of care enoxaparin. The safety of betrixaban will also be studied.

Official Title
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(Apex) Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients

Conditions
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Venous Thromboembolism (VTE)

Intervention / Treatment
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* Drug: Betrixaban
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men and non-pregnant, non-breastfeeding women anticipated to be severely immobilized for at least 24 hours after randomization hospitalized with one of the following congestive heart failure acute respiratory failure, acute infection without septic shock, acute rheumatic disorders acute ischemic stroke with lower extremity hemiparesis or hemi paralysis Exclusion Criteria: a condition requiring prolonged anticoagulation or anti-platelets active bleeding or at high risk of bleeding contraindication to anticoagulant therapy general conditions in which subjects are not suitable to participate in the study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Betrixaban<br>Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days | Drug: Betrixaban<br>* Betrixaban 80 mg PO once daily (QD) for 35 day + 7 days. Enoxaparin Placebo: Once daily, 6-14 days<br>|
| Active Comparator: Enoxaparin<br>Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days | Drug: Enoxaparin<br>* Enoxaparin 40 mg subcutaneous (SC) QD for 10 ± 4 days. Betrixaban Placebo: once daily, 35 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | mITT Cohort 1: Between randomization and Day 47 (max) | 
| 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 | 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). | mITT Cohort 2: Between randomization and Day 47 (max) | 
| mITT: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, VTE-related Death, or Asymptomatic Proximal DVT, Through Visit 3 | 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). | mITT: Between randomization and Day 47 (max) | 
| Percentage of Participants Experiencing Major Bleeding Through Seven Days After Discontinuation of All Study Medication | 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. | Between randomization and Day 49 (max) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mITT Cohort 1: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3 | 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). | mITT Cohort 1: Between randomization and Day 42 (max) | 
| mITT Cohort 2: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3 | 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). | mITT Cohort 2: Between randomization and Day 42 (max) | 
| mITT: Percentage of Participants Experiencing the Composite Event of Symptomatic DVT, Non-fatal PE, or VTE-related Death, Through Visit 3 | 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). | mITT: Between randomization and Day 42 (max) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase III