Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)

Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)

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

Study Overview

• Status: Terminated
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Warfarin; Drug: Apixaban 2.5 MG; Drug: Rivaroxaban 10 MG

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Experiencing Major Bleeding	Major bleeding	Randomization to 12 months
Number of Subjects Experiencing Clinically Relevant Non-major Bleeding	Clinically relevant non-major bleeding	Randomization to 12 months
Number of Subjects With Premature Termination of Study Medication	Premature termination of study medication	Randomization to 12 months
Number of Subjects Experiencing All-cause Mortality	All cause mortality	Randomization to 12 months
Number of Subjects Experiencing Vascular Events (Myocardial Infarction, Ischemic Stroke)	MI, ischemic stroke, peripheral arterial embolism	Randomization to 12 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Thomas Ortel, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (Actual): June 22, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Apixaban; Warfarin
• Other Study ID Numbers: Pro00077510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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