Atrial FibrillationPhase 4COBRRA-AFNCT04642430
COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
A Phase 4 study testing Apixaban and Rivaroxaban in people with Atrial Fibrillation, run by Ottawa Hospital Research Institute at 8 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Apixaban and Rivaroxaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,018 participants
- Where
- 8 sitesCanada
- Study dates
- 6 Jul 2021to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines
Who cannot join
- 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
Show all 9Show fewer
- known liver disease with coagulopathy
- use of contraindicated medications (strong inducers/inhibitors of CYP 3A4/5, P-glycoprotein)
- pregnancy or breastfeeding
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Erin Thomas contact
8 sites in 1 country
Canada8 sites, 7 recruiting
- Recruiting
CISSS de l'Outaouais
Gatineau, Quebec, J8T 4J3
Celine Roy, celine.roy@ssss.gouv.qc.ca
Gladice Salem, gladice_salem@ssss.gouv.qc.ca
- Recruiting
QEII Health Science Centre
Halifax, Nova Scotia
Katie Kawulka, katie.kawulka@nshealth.ca
Ratika Parkash, MD
- Recruiting
Kingston General Hospital
Kingston, Ontario
Huba Rana, huba.rana1@kingstonhsc.ca
Tanya Gilpin, tanya.gilpin@kingstonhsc.ca
- Not yet recruiting
CHU de Quebec - Université Laval
Laval, Quebec
Eric Mercier, MD, eric.mercier@fmed.ulaval.ca
Dr. Eric Mercier, MD
- Recruiting
Ciusss Nim
Montreal, Quebec, H3L 1K5
Dr. Alexis Cournoyer, MD, alexiscournoyermus@gmail.com
Chantal Lanthier, chantal.lanthier.cnmtl@ssss.gouv.qc.ca
- Recruiting
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Daniel Warner, 613-737-8899 ext. 79590, dawarner@ohri.ca
Erin Thomas, erithomas@toh.ca
- Recruiting
University Ottawa Heart Institute
Ottawa, Ontario
Hannah Feagan, 613-696-7000 ext. 14125, hfeagan@ottawaheart.ca
Colleen Ratelle, cratelle@ottawaheart.ca
- Withdrawn
Victoria Cardiac Arrhythmia Trials
Victoria, British Columbia, V8Z 0B9
About this study
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.
Read more
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.
Read the 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
- Being tested
- Apixaban, Rivaroxaban
- Keywords
- Stroke Prevention, Bleed
- Medical subject headings
- Atrial Fibrillation, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
Refer to Apixaban group
RivaroxabanDrug
Also called Xarelto
Refer to Rivaroxaban group
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Rivaroxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: For the duration of the study: 12 months
Secondary outcomes (6)
Adjudicated Major Bleeding events
Major Bleeding includes clinically overt bleeding and is associated with:
- Fatal bleeding, and/or
- Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
- A fall in hemoglobin of ≥20 g/L, or
- Leading to transfusion of ≥2 units of whole blood or red cells.
Measured: For the duration of the study: 12 months
Adjudicated Clinically Relevant Non-Major Bleeding events
Clinically relevant non-major bleeding will be defined as:
- Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria:
- Requiring medical intervention by a healthcare professional
- Leading to hospitalization or increased level of care
- Prompting a face to face (i.e., not just a telephone or electronic communication) evaluation
Measured: For the duration of the study: 12 months
Adjudicated stroke/TIA events
Stroke is defined as non-traumatic focal neurologic deficit lasting ≥ 24 hours and confirmed on cerebral imaging (computed tomography or magnetic resonance imaging).
Transient ischemic attack (TIA) is defined as a temporary loss of blood flow to a part of the brain with focal neurologic deficit lasting < 24 hours without imaging evidence of acute infarction.
Strokes are to be classified as ischemic, hemorrhagic stroke, or uncertain. Hemorrhagic strokes are considered and will be reported as both bleeding events as well as stroke endpoints. The location of the bleeding can be determined from the diagnostic imaging reports.
Measured: For the duration of the study: 12 months
All-cause mortality
Using a binary outcome of an event or no event (Individual rates of death, all causes).
Measured: For the duration of the study: 12 months
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
Measured: For the duration of the study: 12 months
Incremental cost-effectiveness ratio
We will model the prognosis of a cohort of patients receiving rivaroxaban versus apixaban. The results will be presented as incremental cost per QALY gained, incremental costs per one clinically relevant bleeding cases prevented, and incremental cost per one life year saved.
Measured: For the duration of the study: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2020
- Study start6 Jul 2021
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A pragmatic prospective randomized open blinded endpoint (PROBE) trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,018 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Lana Castellucci, MD, FRCPC, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04642430
- Sponsor's protocol ID
- COBRRA-AF
- Acronym
- COBRRA-AF
- Status last verified
- Sep 2026
- First submitted
- 19 Nov 2020
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT04642430
- Acronym / sponsor ID
- COBRRA-AF / COBRRA-AF
- Conditions
- Atrial Fibrillation
- Keywords
- Stroke Prevention, Bleed
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3,018 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network, Canadian Institutes of Health Research (CIHR)
- Study start
- 6 Jul 2021 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 24 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A pragmatic prospective randomized open blinded endpoint (PROBE) trial
| Arm | Type | Receives |
|---|---|---|
| Apixaban group | Active comparator | Drug: Apixaban5 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 |
| Rivaroxaban Group | Active comparator | Drug: Rivaroxaban20 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years old
- Confirmed new diagnosis of AF on ECG with an indication to start anticoagulation according to Canadian Cardiovascular Society guidelines
Key exclusion criteria (9 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: EliquisRefer to Apixaban group | Drug | Apixaban group |
| RivaroxabanAlso: XareltoRefer to Rivaroxaban group | Drug | Rivaroxaban Group |
Primary outcome
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
6 secondary outcomes
Adjudicated Major Bleeding events
Time frame: For the duration of the study: 12 months
Adjudicated Clinically Relevant Non-Major Bleeding events
Time frame: For the duration of the study: 12 months
Adjudicated stroke/TIA events
Time frame: For the duration of the study: 12 months
All-cause mortality
Time frame: For the duration of the study: 12 months
Medication adherence
Time frame: For the duration of the study: 12 months
Incremental cost-effectiveness ratio
Time frame: For the duration of the study: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Atrial Fibrillation
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Erin Thomas contact
Lana Castellucci, MD, FRCPC principal investigator
Ottawa Hospital Research Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Apixaban and Rivaroxaban in people with Atrial Fibrillation, run by Ottawa Hospital Research Institute at 8 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lana Castellucci, MD (613-737-8899 ext. 75481, lcastellucci@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of adjudicated clinically relevant bleeding (CRB) events (time frame: For the duration of the study: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.