We are pleased to introduce The COVET Trial (Comparison of Oral anticoagulants for extended VEnous Thromboembolism), sponsored by PCORI. Experienced research investigators and research centers that have participated in similar sized trials are needed to ensure the success of this trial. Below is a description of The COVET Trial.
We will be hosting a meeting at the AC Forum National Conference in Los Angeles on April 20 at 9:30-11:30 and a poster on April 20 between 4:30-6 pm (Poster J3; Diamond Ballroom 5-10) and invite you to join in the discussions.
Background and Significance: Patients with acute unprovoked venous thromboembolism (VTE) require 3-6 months of anticoagulation. The risk of recurrent VTE (rVTE) in these patients is substantial, up to 10% in the first year after stopping anticoagulation and the annual risk of major hemorrhage on anticoagulation is approximately 2%. Guidelines suggest continuing anticoagulation long term reduces that risk, provided that patients have low risk of bleeding. The next crucial question becomes which anticoagulant to choose. Warfarin has been the standard anticoagulant for decades for treatment of VTE. Direct oral anticoagulants (DOACs) have been compared to warfarin for treatment of acute VTE and are at least as safe and effective. There are no direct comparison trials evaluating the safety and efficacy of rivaroxaban and apixaban, two DOACs targeting Factor Xa, to warfarin for patients who remain on lifelong anticoagulation.
The question to be addressed is: In patients with unprovoked VTE who have completed 3-6 months of initial anticoagulation treatment and need prolonged therapy, which of the following options is superior to standard anticoagulation therapy with warfarin with target INR 2-3: 1) Apixaban 2.5 mg BID, or 2) Rivaroxaban 20 mg daily?
Study Aim: This comparative effectiveness research (CER) trial will aim to determine whether apixaban and/or rivaroxaban is safer than VKA in patients at high risk for rVTE and remain on long term anticoagulation. This will inform patients, clinicians, and policy makers allowing therapeutic approaches to be tailored to individual patients.
Study Description: We propose a pragmatic, prospective, randomized, open, blinded end-point (PROBE) trial. The proposed intervention arms are a) warfarin once daily for target INR 2-3; b) rivaroxaban 20 mg daily; and c) apixaban 2.5 mg BID, for 12 months of anticoagulation and follow up. Patients to be included are adults with confirmed symptomatic and unprovoked DVT/PE, previously treated with oral anticoagulation for 3-6 months, and at high risk for rVTE. Patients will be excluded if they have creatinine clearance (CrCl) < 30 mL/min, liver disease, or life expectancy < 3 months. Patients will be recruited from out-patient clinical settings.
The proposed sample size is 1055 patients per treatment arm (3165 total) to be recruited over 3 years.
The primary outcome will be a composite bleeding outcome (major bleeding or clinically relevant non-major bleeding).
Study Investigators and Research Centers: Given the large sample size needed for this study, we anticipate needing 40-60 experienced recruiting centers in the United States and Canada.
If you are interested in participating, please contact:
Lana Castellucci MD, FRCPC, MSc
Assistant Professor, University of Ottawa, Faculty of Medicine, Department of Medicine
Email: firstname.lastname@example.org Tel: 613-737-8899 ext. 71069; Fax: 613-739-6837
Many thanks for your interest in this pragmatic and practice-changing trial.
Lana A. Castellucci, David Garcia, Thomas L. Ortel