This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation (COBRRA-AF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04642430
Recruitment Status : Recruiting
First Posted : November 24, 2020
Last Update Posted : October 6, 2023
Sponsor:
Collaborators:
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

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.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Apixaban Drug: Rivaroxaban Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3018 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A pragmatic prospective randomized open blinded endpoint (PROBE) trial
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
Actual Study Start Date : July 6, 2021
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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

Drug: Apixaban
Refer to Apixaban group
Other Name: Eliquis

Active Comparator: 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

Drug: Rivaroxaban
Refer to Rivaroxaban group
Other Name: Xarelto




Primary Outcome Measures :
  1. The rate of adjudicated clinically relevant bleeding (CRB) events [ Time Frame: For the duration of the study: 12 months ]
    CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events


Secondary Outcome Measures :
  1. Adjudicated Major Bleeding events [ Time Frame: For the duration of the study: 12 months ]
  2. Adjudicated Clinically Relevant Non-Major Bleeding events [ Time Frame: For the duration of the study: 12 months ]
  3. Adjudicated stroke events [ Time Frame: For the duration of the study: 12 months ]
  4. All-cause mortality [ Time Frame: For the duration of the study: 12 months ]
  5. Medication adherence [ Time Frame: For the duration of the study: 12 months ]
    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

  6. cost per one CRB case prevented [ Time Frame: For the duration of the study: 12 months ]
  7. cost per one life year saved [ Time Frame: For the duration of the study: 12 months ]
  8. cost per one quality-adjusted life year (QALY) gained [ Time Frame: For the duration of the study: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04642430


Contacts
Layout table for location contacts
Contact: Lana Castellucci, MD, FRCPC 613-737-8899 ext 74641 lcastellucci@toh.ca
Contact: Erin Thomas 613-737-8899 ext 71068 erithomas@toh.ca

Locations
Layout table for location information
Canada, Nova Scotia
QEII Health Science Centre Not yet recruiting
Halifax, Nova Scotia, Canada
Contact: Ratika Parkash, MD         
Canada, Ontario
Kingston General Hospital Recruiting
Kingston, Ontario, Canada
Contact: Kerstin deWit, MD         
The Ottawa Hospital - General Campus Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Lana Castellucci, MD, FRCPC       lcastellucci@toh.ca   
Contact: Erin Thomas    613-737-8899 ext 71068    erithomas@toh.ca   
University Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada
Contact: Daniel Ramirez, MD         
Canada, Quebec
Université Laval Not yet recruiting
Québec, Quebec, Canada
Contact: Eric Mercier, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
Canadian Institutes of Health Research (CIHR)
Investigators
Layout table for investigator information
Principal Investigator: Lana Castellucci, MD, FRCPC Ottawa Hospital Research Institute
Layout table for additonal information
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT04642430    
Other Study ID Numbers: COBRRA-AF
First Posted: November 24, 2020    Key Record Dates
Last Update Posted: October 6, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ottawa Hospital Research Institute:
Stroke Prevention
Bleed
Additional relevant MeSH terms:
Layout table for MeSH terms
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Rivaroxaban
Apixaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants