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

Primary Purpose

Atrial Fibrillation

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Apixaban
Rivaroxaban
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Stroke Prevention, Bleed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • QEII Health Science Centre
  • Kingston General HospitalRecruiting
  • The Ottawa Hospital - General CampusRecruiting
  • University Ottawa Heart InstituteRecruiting
  • Université Laval

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Apixaban group

Rivaroxaban Group

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Adjudicated Major Bleeding events
Adjudicated Clinically Relevant Non-Major Bleeding events
Adjudicated stroke events
All-cause mortality
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
cost per one CRB case prevented
cost per one life year saved
cost per one quality-adjusted life year (QALY) gained

Full Information

First Posted
November 19, 2020
Last Updated
October 3, 2023
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network, Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT04642430
Brief Title
COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
Acronym
COBRRA-AF
Official Title
COmparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network, Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
Stroke Prevention, Bleed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A pragmatic prospective randomized open blinded endpoint (PROBE) trial
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
3018 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Apixaban group
Arm Type
Active Comparator
Arm Description
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
Arm Title
Rivaroxaban Group
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
Eliquis
Intervention Description
Refer to Apixaban group
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Xarelto
Intervention Description
Refer to Rivaroxaban group
Primary Outcome Measure Information:
Title
The rate of adjudicated clinically relevant bleeding (CRB) events
Description
CRB events are defined as the composite of major bleeding (MB) events and clinically relevant non-major bleeding (CRNMB) events
Time Frame
For the duration of the study: 12 months
Secondary Outcome Measure Information:
Title
Adjudicated Major Bleeding events
Time Frame
For the duration of the study: 12 months
Title
Adjudicated Clinically Relevant Non-Major Bleeding events
Time Frame
For the duration of the study: 12 months
Title
Adjudicated stroke events
Time Frame
For the duration of the study: 12 months
Title
All-cause mortality
Time Frame
For the duration of the study: 12 months
Title
Medication adherence
Description
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
Time Frame
For the duration of the study: 12 months
Title
cost per one CRB case prevented
Time Frame
For the duration of the study: 12 months
Title
cost per one life year saved
Time Frame
For the duration of the study: 12 months
Title
cost per one quality-adjusted life year (QALY) gained
Time Frame
For the duration of the study: 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lana Castellucci, MD, FRCPC
Phone
613-737-8899
Ext
74641
Email
lcastellucci@toh.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Erin Thomas
Phone
613-737-8899
Ext
71068
Email
erithomas@toh.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lana Castellucci, MD, FRCPC
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
QEII Health Science Centre
City
Halifax
State/Province
Nova Scotia
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ratika Parkash, MD
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kerstin deWit, MD
Facility Name
The Ottawa Hospital - General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lana Castellucci, MD, FRCPC
Email
lcastellucci@toh.ca
First Name & Middle Initial & Last Name & Degree
Erin Thomas
Phone
613-737-8899
Ext
71068
Email
erithomas@toh.ca
Facility Name
University Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Ramirez, MD
Facility Name
Université Laval
City
Québec
State/Province
Quebec
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Mercier, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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