COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— COBRRA-AF  

Official title:

COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04642430
• Other study ID #: COBRRA-AF
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2021
• Est. completion date: December 31, 2026

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
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3018
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years old

• Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines

Exclusion Criteria:

• Creatinine clearance =<15 ml/min calculated using 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

• history of mechanical valve

• other indication for anticoagulation (e.g. mechanical valves, venous thrombosis)

• dual antiplatelet agent use

• known liver disease with coagulopathy

• use of contraindicated medications (strong inducers/inhibitors of CYP 3A4/5, P-glycoprotein)

• pregnancy or breastfeeding

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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

Locations

Country	Name	City	State
Canada	CISSS de l'Outaouais	Gatineau	Quebec
Canada	QEII Health Science Centre	Halifax	Nova Scotia
Canada	Kingston General Hospital	Kingston	Ontario
Canada	CHU de Quebec - Université Laval	Laval	Quebec
Canada	Ciusss Nim	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	University Ottawa Heart Institute	Ottawa	Ontario
Canada	Victoria Cardiac Arrhythmia Trials	Victoria	British Columbia

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

Country where clinical trial is conducted

Canada, 

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: 12 months
Secondary	Adjudicated Major Bleeding events		For the duration of the study: 12 months
Secondary	Adjudicated Clinically Relevant Non-Major Bleeding events		For the duration of the study: 12 months
Secondary	Adjudicated stroke events		For the duration of the study: 12 months
Secondary	All-cause mortality		For the duration of the study: 12 months
Secondary	Medication adherence	Reported as the number of patients self-reporting "all assigned medications were taken" "missing at least one dose of study medication", or "not able to take all of the study medications" out of the total number of medication compliance assessments done respectively	For the duration of the study: 12 months
Secondary	cost per one CRB case prevented		For the duration of the study: 12 months
Secondary	cost per one life year saved		For the duration of the study: 12 months
Secondary	cost per one quality-adjusted life year (QALY) gained		For the duration of the study: 12 months