Clinical trial NCT04642430: COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
Official title: COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: Stroke Prevention
Bleed
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
name: Canadian Institutes of Health Research (CIHR)
First posted: 2020-11-24
Enrollment: 3018
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A pragmatic prospective randomized open blinded endpoint (PROBE) trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The rate of adjudicated clinically relevant bleeding (CRB) events
timeFrame: For the duration of the study: 12 months
Secondary outcomes:
measure: Adjudicated Major Bleeding events
timeFrame: For the duration of the study: 12 months
measure: Adjudicated Clinically Relevant Non-Major Bleeding events
timeFrame: For the duration of the study: 12 months
measure: Adjudicated stroke/TIA events
timeFrame: For the duration of the study: 12 months
measure: All-cause mortality
timeFrame: For the duration of the study: 12 months
measure: Medication adherence
timeFrame: For the duration of the study: 12 months
measure: Incremental cost-effectiveness ratio
timeFrame: For the duration of the study: 12 months
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Science Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Ottawa
country: Canada
facility: University Ottawa Heart Institute
state: Ontario
city: Gatineau
country: Canada
facility: CISSS de l'Outaouais
state: Quebec
city: Laval
country: Canada
facility: CHU de Quebec - Université Laval
state: Quebec
city: Montreal
country: Canada
facility: Ciusss Nim
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Lana Castellucci, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: