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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03266783
Other study ID # COBRRA
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date December 13, 2017
Est. completion date December 2024

Study information

Verified date April 2024
Source Ottawa Hospital Research Institute
Contact Lana Castellucci, MD, FRCPC
Phone 613-737-8899
Email lcastellucci@toh.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Apixaban and rivaroxaban have been compared to standard therapy for treatment of acute symptomatic venous thromboembolism (VTE) in randomized controlled trials (RCTs), and are both approved by Health Canada. No safety or efficacy data is available from direct head-to-head comparison of these two anticoagulants. Lawsuits in the United States over bleeding events, patient perceptions, and concerns with medication adherence are additional factors highlighting the importance of a comparison trial. This multi-center, pragmatic, prospective, randomized, open-label, blinded end-point (PROBE) trial aims to compare the safety of apixaban and rivaroxaban for the treatment of VTE.


Description:

VTE is the third leading cause of mortality by cardiovascular disease. Standard treatment for acute VTE uses a combination of parenteral Low-Molecular-Weight Heparin (LMWH) and oral vitamin K antagonists (VKA) for 3 months, and carries significant bleeding risk. The major and/or clinically-relevant non-major bleeding (CRNMB) event rate is reported between 8.1-9.7% during initial treatment. This treatment is burdensome owing to subcutaneous injections, drug interactions, and laboratory monitoring. Direct oral anticoagulants (DOACs) are simpler to use and do not require laboratory monitoring. Rivaroxaban and apixaban are two DOACs targeting Factor Xa. Each DOAC was separately proven effective and safe when compared to standard treatment. Comparison of the bleeding rates between studies would favour use of apixaban over rivaroxaban; however, trial limitations and lack of direct comparison between these two agents makes it impossible to draw firm conclusions. This represents a dilemma in clinical practice because the absence of convincing differences in safety has led to genuine uncertainty about which DOAC has the best risk-to-benefit ratio. To address these limitations, a head-to-head randomized controlled trial (RCT) is needed to determine the safety (i.e. bleeding risk) of twice daily apixaban over once daily rivaroxaban during the first 3 months of acute VTE treatment. Eligibility criteria will be less stringent than the COBRRA pilot study and reflect real-world patients. Cost-effective analysis of apixaban twice daily compared to rivaroxaban once daily will also be performed.


Recruitment information / eligibility

Status Recruiting
Enrollment 2760
Est. completion date December 2024
Est. primary completion date August 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Confirmed newly diagnosed symptomatic acute venous thromboembolism (VTE) [proximal lower extremity deep vein thrombosis (DVT) or segmental or greater pulmonary embolism (PE)] - Age = 18 years old - Informed consent obtained Exclusion Criteria: - Have received > 72 hours of therapeutic anticoagulation - Creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula - Any contraindication for anticoagulation with apixaban or rivaroxaban as determined by the treating physician such as, but not limited to: - active bleeding, - active malignancy, defined as a) diagnosed with cancer within the past 6 months; or b) recurrent, regionally advanced or metastatic disease; or c) currently receiving treatment or have received any treatment for cancer during the 6 months prior to randomization; or d) a hematologic malignancy not in complete remission, - weight > 120 kg, - liver disease (Child-Pugh Class B or C), - use of contraindicated medications - another indication for long-term anticoagulation (e.g. atrial fibrillation) - pregnant (note below) or breastfeeding (Note: as reported by the patient or a pregnancy test will be ordered at the discretion of the treating physician for women of childbearing potential as per standard of care)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Apixaban
Refer to Apixaban group
Rivaroxaban
Refer to Rivaroxaban group

Locations

Country Name City State
Australia The University of Sydney Darlington New South Wales
Canada University of Calgary Calgary Alberta
Canada Alberta Health Sciences Edmonton Alberta
Canada QEII Health Science Centre Halifax Nova Scotia
Canada Hamilton General Hospital Hamilton Ontario
Canada Juravinski Hospital Hamilton Ontario
Canada St. Joseph's Healthcare Hamilton Hamilton Ontario
Canada Kingston General Hospital Kingston Ontario
Canada London Health Sciences Center London Ontario
Canada Hôpital Sacré-Coeur de Montréal Montreal Quebec
Canada St. Mary's Hospital Montreal Quebec
Canada Jewish General Hospital Montréal Quebec
Canada McGill University Health Center Montréal Quebec
Canada The Ottawa Hospital - General Campus Ottawa Ontario
Canada CHU de Québec-Université Laval Quebec city Quebec
Canada University of Sherbrooke Sherbrooke Quebec
Canada UHN - Toronto General Hospital Toronto Ontario
Canada St. Paul's Hospital Vancouver British Columbia
Ireland The Royal College of Surgeons in Ireland/Mater Misericordiae University Hospital Dublin

Sponsors (3)

Lead Sponsor Collaborator
Ottawa Hospital Research Institute Canadian Institutes of Health Research (CIHR), Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Countries where clinical trial is conducted

Australia,  Canada,  Ireland, 

Outcome

Type Measure Description Time frame Safety issue
Primary The rate of adjudicated clinically relevant bleeding (CRB) events CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events. For the duration of the study: 3 months
Secondary Adjudicated Major Bleeding events For the duration of the study: 3 months
Secondary Adjudicated Clinically Relevant Non-Major Bleeding events For the duration of the study: 3 months
Secondary Adjudicated recurrent VTE events For the duration of the study: 3 months
Secondary Adjudicated VTE-related deaths For the duration of the study: 3 months
Secondary All-cause mortality For the duration of the study: 3 months
Secondary Medication adherence For the duration of the study: 3 months
Secondary Quality-adjusted life years (QALYs) gained For the duration of the study: 3 months
Secondary Incremental cost-effectiveness ratio For the duration of the study: 3 months
Secondary Impact of verbal consent on patient participation in comparison with participants from sites using written informed consent For the duration of the study: 3 months
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