Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism

Study Overview
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Brief Summary
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Comparison of Oral anticoagulants (warfarin, apixaban and rivaroxaban) for extended VEnous Thromboembolism.

Detailed Description
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Determine if apixaban is superior to warfarin in the reduction of clinically relevant bleeding. Determine if rivaroxaban is superior to warfarin in the reduction of clinically relevant bleeding. Determine if apixaban is non-inferior to warfarin in the prevention of recurrent venous thromboembolism. Determine if rivaroxaban is non-inferior to warfarin in the prevention of recurrent venous thromboembolism. An exploratory comparison of apixaban versus rivaroxaban for the prevention of clinically relevant bleeding and recurrent Venous Thromboembolism (VTEs) as a secondary objective.

Official Title
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Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Warfarin
* Drug: Apixaban 2.5 MG
* Drug: Rivaroxaban 10 MG


Participation Criteria
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Eligibility Criteria
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3.1 Inclusion Criteria To be eligible for this trial, patients must meet all of the following criteria: Have confirmed acute, symptomatic, first lower extremity proximal DVT and/or PE that is NOT associated with a transient risk factor. Have completed an initial treatment course of oral anticoagulant therapy for 3-12 months and have a recommendation from their provider to continue anticoagulation indefinitely. Have the capacity to understand and sign an informed consent form. Be 18 years of age and older. Under the direct care of a healthcare provider for treatment of VTE for the length of time in the study. 3.2 Exclusion Criteria If a patient meets any of the following criteria, he or she may not be enrolled in the study: Creatinine clearance (CrCl) < 30 mL/min as determined by Cockcroft-Gault formula documented within 3 months from date of consent Significant liver disease (Child-Pugh B or C) Concomitant use of medications that are strong P-glycoprotein or CYP3A4 inducers/inhibitors Another indication for chronic therapeutic-dose anticoagulation, such as atrial fibrillation (i.e., rivaroxaban, 10 mg daily, or apixaban, 2.5 mg twice daily, would not be appropriate therapy) A clinical indication for a specific anticoagulant regimen (e.g., warfarin with a target INR of 2-3 is recommended for patients with 'triple-positive' antiphospholipid syndrome). Life expectancy < 3 months Currently pregnant or breast feeding Unable / unwilling to pay for one (or more) of the treatment options Active Cancer defined as: Diagnosed with cancer within the past 6 months; or Recurrent, regionally advanced or metastatic disease; Currently receiving treatment or have received any treatment for cancer during the 6 months prior to randomization; or A hematologic malignancy not in complete remission • Unwilling / unlikely to agree to follow up

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Warfarin<br>Subjects randomized to Warfarin will have warfarin administered daily in order to maintain a target INR of 2-3 | Drug: Warfarin<br>* Will be randomized to receive open label warfarin daily to achieve a target INR of 2-3<br>|
| Active Comparator: Apixaban<br>Subjects randomized to Apixaban will have apixaban administered study drug of 2.5mg twice daily | Drug: Apixaban 2.5 MG<br>* Will be randomized to receive open label apixaban of 2.5 mg twice daily<br>|
| Active Comparator: Rivaroxaban<br>Subjects randomized to Rivaroxaban will have rivaroxaban administered study drug of 10 mg daily | Drug: Rivaroxaban 10 MG<br>* Will be randomized to receive open label rivaroxaban of 10mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Clinically Relevant Bleeding Events | Primary outcome of Clinically relevant bleeding (composite of major bleeding (MB) and/or clinically relevant non major bleeding (CRNMB)) | Randomization to 12 months | 
| Number of Subjects With Recurrent Venous Thromboembolism (VTE) | Primary efficacy outcome of recurrent VTE | Randomization to 12 months |