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Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)

Primary Purpose

Venous Thromboembolism

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Warfarin
Apixaban 2.5 MG
Rivaroxaban 10 MG
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Venous Thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California Irvine Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Warfarin

Apixaban

Rivaroxaban

Arm Description

Subjects randomized to Warfarin will have warfarin administered daily in order to maintain a target INR of 2-3

Subjects randomized to Apixaban will have apixaban administered study drug of 2.5mg twice daily

Subjects randomized to Rivaroxaban will have rivaroxaban administered study drug of 10 mg daily

Outcomes

Primary Outcome Measures

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))
Number of Subjects With Recurrent Venous Thromboembolism (VTE)
Primary efficacy outcome of recurrent VTE

Secondary Outcome Measures

Full Information

First Posted
June 20, 2017
Last Updated
December 12, 2019
Sponsor
Duke University
Collaborators
Patient-Centered Outcomes Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03196349
Brief Title
Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
Acronym
COVET
Official Title
Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment
Study Start Date
August 1, 2018 (Actual)
Primary Completion Date
May 1, 2019 (Actual)
Study Completion Date
May 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Patient-Centered Outcomes Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Warfarin
Arm Type
Active Comparator
Arm Description
Subjects randomized to Warfarin will have warfarin administered daily in order to maintain a target INR of 2-3
Arm Title
Apixaban
Arm Type
Active Comparator
Arm Description
Subjects randomized to Apixaban will have apixaban administered study drug of 2.5mg twice daily
Arm Title
Rivaroxaban
Arm Type
Active Comparator
Arm Description
Subjects randomized to Rivaroxaban will have rivaroxaban administered study drug of 10 mg daily
Intervention Type
Drug
Intervention Name(s)
Warfarin
Intervention Description
Will be randomized to receive open label warfarin daily to achieve a target INR of 2-3
Intervention Type
Drug
Intervention Name(s)
Apixaban 2.5 MG
Intervention Description
Will be randomized to receive open label apixaban of 2.5 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 10 MG
Intervention Description
Will be randomized to receive open label rivaroxaban of 10mg daily
Primary Outcome Measure Information:
Title
Number of Subjects With Clinically Relevant Bleeding Events
Description
Primary outcome of Clinically relevant bleeding (composite of major bleeding (MB) and/or clinically relevant non major bleeding (CRNMB))
Time Frame
Randomization to 12 months
Title
Number of Subjects With Recurrent Venous Thromboembolism (VTE)
Description
Primary efficacy outcome of recurrent VTE
Time Frame
Randomization to 12 months
Other Pre-specified Outcome Measures:
Title
Number of Subjects Experiencing Major Bleeding
Description
Major bleeding
Time Frame
Randomization to 12 months
Title
Number of Subjects Experiencing Clinically Relevant Non-major Bleeding
Description
Clinically relevant non-major bleeding
Time Frame
Randomization to 12 months
Title
Number of Subjects With Premature Termination of Study Medication
Description
Premature termination of study medication
Time Frame
Randomization to 12 months
Title
Number of Subjects Experiencing All-cause Mortality
Description
All cause mortality
Time Frame
Randomization to 12 months
Title
Number of Subjects Experiencing Vascular Events (Myocardial Infarction, Ischemic Stroke)
Description
MI, ischemic stroke, peripheral arterial embolism
Time Frame
Randomization to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Ortel, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism

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