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

NCT ID: NCT04642430

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 3018 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-06
• Study Completion Date: 2027-12-31

Brief 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.

Detailed 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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Apixaban group

5 mg PO, twice daily for 12 months of treatment. A dose reduction* to 2.5 mg twice daily will apply if patients meet 2 of 3 following criteria: age > 80 years; weight < 60 kg; creatinine >133 micromol/L.

*Patients with AF who are receiving DOAC should have their renal function assessed at baseline and at least annually

Group Type: ACTIVE_COMPARATOR

Apixaban

Intervention Type: DRUG

Refer to Apixaban group

Rivaroxaban Group

20 mg PO, once daily for 12 months of treatment. A dose reduction* to 15 mg daily will apply to patients with creatinine clearance <50 ml/min.

*Patients with AF who are receiving DOAC should have their renal function assessed at baseline and at least annually

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

Refer to Rivaroxaban group

Interventions

Apixaban

Refer to Apixaban group

Intervention Type: DRUG

Rivaroxaban

Refer to Rivaroxaban group

Intervention Type: DRUG

Other Intervention Names

Eliquis; Xarelto

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

NETWORK

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lana Castellucci, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Victoria Cardiac Arrhythmia Trials

Victoria, British Columbia, Canada

Site Status: RECRUITING

QEII Health Science Centre

Halifax, Nova Scotia, Canada

Site Status: RECRUITING

Kingston General Hospital

Kingston, Ontario, Canada

Site Status: RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Site Status: RECRUITING

University Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status: RECRUITING

CISSS de l'Outaouais

Gatineau, Quebec, Canada

Site Status: RECRUITING

CHU de Quebec - Université Laval

Laval, Quebec, Canada

Site Status: NOT_YET_RECRUITING

Ciusss Nim

Montreal, Quebec, Canada

Site Status: NOT_YET_RECRUITING

Countries

Canada

Central Contacts

Lana Castellucci, MD, FRCPC

Role: CONTACT

lcastellucci@toh.ca

613-737-8899 ext. 74641

Erin Thomas

Role: CONTACT

erithomas@toh.ca

613-737-8899 ext. 79714

Facility Contacts

Matthew Coxon

Role: primary

mcoxon@catrials.org

May Woodburn

Role: backup

mwoodburn@catrials.org

Ratika Parkash, MD

Role: primary

Kerstin deWit, MD

Role: primary

Lana Castellucci, MD, FRCPC

Role: primary

lcastellucci@toh.ca

Erin Thomas

Role: backup

erithomas@toh.ca

613-737-8899 ext. 79714

Daniel Ramirez, MD

Role: primary

Celine Roy

Role: primary

celine.roy@ssss.gouv.qc.ca

Gladice Salem

Role: backup

gladice_salem@ssss.gouv.qc.ca

Eric Mercier, MD

Role: primary

eric.mercier@fmed.ulaval.ca

Dr. Alexis Cournoyer, MD

Role: primary

alexiscournoyermus@gmail.com

Chantal Lanthier

Role: backup

chantal.lanthier.cnmtl@ssss.gouv.qc.ca

Other Identifiers

COBRRA-AF

Identifier Type: -

Identifier Source: org_study_id