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

NCT04642430 | Recruiting Phase 4 DMC

• 1 other identifier: COBRRA-AF
• Study Type: interventional
• Target: 3,018
• Locations: 1 country
• Sites: 8

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.

Conditions

Atrial Fibrillation

Keywords

Stroke Prevention; Bleed

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Adjudicated Major Bleeding events

  For the duration of the study: 12 months

• Adjudicated Clinically Relevant Non-Major Bleeding events

  For the duration of the study: 12 months

• Adjudicated stroke/TIA events

  For the duration of the study: 12 months

• All-cause mortality

  For the duration of the study: 12 months

• Medication adherence

  For the duration of the study: 12 months

Study Arms (2)

Apixaban group

ACTIVE COMPARATOR

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

Drug: Apixaban

Rivaroxaban Group

ACTIVE COMPARATOR

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

Drug: Rivaroxaban

Interventions

Apixaban DRUG

Refer to Apixaban group

Also known as: Eliquis

Apixaban group

Rivaroxaban DRUG

Refer to Rivaroxaban group

Also known as: Xarelto

Rivaroxaban Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (8)

Victoria Cardiac Arrhythmia Trials

Victoria, British Columbia, V8Z 0B9, Canada

RECRUITING

QEII Health Science Centre

Halifax, Nova Scotia, Canada

RECRUITING

Kingston General Hospital

Kingston, Ontario, Canada

RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

University Ottawa Heart Institute

Ottawa, Ontario, Canada

RECRUITING

CISSS de l'Outaouais

Gatineau, Quebec, J8T 4J3, Canada

RECRUITING

CHU de Quebec - Université Laval

Laval, Quebec, Canada

NOT YET RECRUITING

Ciusss Nim

Montreal, Quebec, H3L 1K5, Canada

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Hemorrhage

Interventions

apixaban; Rivaroxaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lana Castellucci, MD, FRCPC

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lana Castellucci, MD, FRCPC

CONTACT

613-737-8899; lcastellucci@toh.ca

Erin Thomas

CONTACT

613-737-8899; erithomas@toh.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A pragmatic prospective randomized open blinded endpoint (PROBE) trial

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: November 24, 2020
• Study Start: July 6, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8)