COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation (COBRRA-AF)
Sponsor: Canadian Institutes of Health Research (CIHR)
Listed as NCT04642430, this observational or N/A phase trial focuses on Atrial Fibrillation and remains actively recruiting participants. Sponsored by Canadian Institutes of Health Research (CIHR), it has been updated 15 times since 2021, reflecting substantial change activity. This study contributes longitudinal data to the cardiovascular research landscape.
Study Description(click to expand)Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Oral anticoagulants such as Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are highly effective at reducing the risk of stroke by up to 95%. Randomized controlled trials (RCTs) have compared apixaban and rivaroxaban (both DOACs) to VKAs for stroke prevention in AF, and are approved for this use by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF, patient values around bleeding, and litigation highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.
The objective of this RCT is to compare the safety of the first 12 months of apixaban twice daily to rivaroxaban once daily in patients with non-valvular AF (NVAF). Patients will be monitored for the primary outcome of clinically relevant bleeding (CRB; a composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events during follow-up. This trial will directly inform clinical practice and the choice of first-line therapy.
Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Oral anticoagulants such as Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are highly effective at reducing the risk of stroke by up to 95%. Randomized controlled trials (RCTs) have compared apixaban and rivaroxaban (both DOACs) to VKAs for stroke prevention in AF, and are approved for this use by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF, patient values around bleeding, and litigation highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm.
The objective of this RCT is to compare the safety of the first 12 months of apixaban twice daily to rivaroxaban once daily in patients with non-valvular AF (NVAF). Patients will be monitored for the primary outcome of clinically relevant bleeding (CRB; a composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events during follow-up. This trial will directly inform clinical practice and the choice of first-line therapy.
Status Flow
Change History
15 versions recorded-
Apr 23, 2026 — Present [daily]
Recruiting
Phase: PHASE4 → None
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Dec 2025 — Apr 2026 [monthly]
Recruiting PHASE4
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May 2025 — Dec 2025 [monthly]
Recruiting PHASE4
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Nov 2024 — May 2025 [monthly]
Recruiting PHASE4
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Sep 2024 — Nov 2024 [monthly]
Recruiting PHASE4
▶ Show 10 earlier versions
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Jul 2024 — Sep 2024 [monthly]
Recruiting PHASE4
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May 2024 — Jul 2024 [monthly]
Recruiting PHASE4
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Nov 2023 — May 2024 [monthly]
Recruiting PHASE4
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May 2023 — Nov 2023 [monthly]
Recruiting PHASE4
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Apr 2022 — May 2023 [monthly]
Recruiting PHASE4
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Dec 2021 — Apr 2022 [monthly]
Recruiting PHASE4
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Oct 2021 — Dec 2021 [monthly]
Recruiting PHASE4
Status: Not Yet Recruiting → Recruiting
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Mar 2021 — Oct 2021 [monthly]
Not Yet Recruiting PHASE4
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Jan 2021 — Mar 2021 [monthly]
Not Yet Recruiting PHASE4
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Dec 2020 — Jan 2021 [monthly]
Not Yet Recruiting PHASE4
First recorded
Eligibility Summary
Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Having a stroke can affect a patient's ability to speak, eat, walk, work, care for themselves, and interact with others. Not only can it ruin one's life, but it can also be fatal. A stroke occurs when blood flow to the brain is blocked by a clot, depriving brain cells of oxygen. In people with atrial fibrillation, blood flow is sluggish in the top chambers of the heart, and blood clots can form there. When a piece of a clot breaks off, it can travel to the brain and cause a stroke. That's where blood thinners come in. Blood thinners, or anticoagulants, decrease the chances of blood clots forming in the heart, reducing the risk of stroke. Studies show that blood thinners are highly effective at reducing the risk of stroke by up to 95%. The conventional blood thinner is warfarin, taken by mouth. Warfarin requires regular blood tests to make sure a patient getting the correct dose. The patient also may have to avoid certain foods since the medication can interact with them. Newer blood thinners, known as direct-oral anticoagulants (DOACs) are available, which do not require regular blood tests and do not interact with foods. Two of the new blood thinners are called rivaroxaban and apixaban. Like warfarin, they can be taken by mouth, and studies have shown them to be as effective as warfarin. Both rivaroxaban and apixaban have been approved for stroke prevention in AF by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF and patient values around bleeding highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm. The trial is to assess bleeding rates and superiority of using apixaban versus rivaroxaban in patients with non-valvular atrial fibrillation.
Contact Information
- Canadian Institutes of Health Research (CIHR)
- Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
- Ottawa Hospital Research Institute
For direct contact, visit the study record on ClinicalTrials.gov .