NCT03266783

Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 2,760 (actual)
• Sponsor: Ottawa Hospital Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Venous Thromboembolism

Interventions

Type	Name	Description
DRUG	Apixaban	Refer to Apixaban group
DRUG	Rivaroxaban	Refer to Rivaroxaban group

Timeline

• Start date: 2017-12-13
• Primary completion: 2025-04-30
• Completion: 2025-09-08
• First posted: 2017-08-30
• Last updated: 2025-11-17

Locations

19 sites across 3 countries: Australia, Canada, Ireland