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ATRIAL FIBRILLATIONPhase 3BRAIN-AFNCT02387229

Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in AF

A Phase 3 study testing Rivaroxaban in people with ATRIAL FIBRILLATION, run by Montreal Heart Institute at 41 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a prospective, multicenter, randomized, double-blinded clinical trial exploring the efficacy and safety of rivaroxaban as compared to standard of care in reducing stroke, transient ischemic attack (TIA) and neurocognitive decline, in subjects with non-valvular AF and with low risk of stroke. Read more about this study

Who is it for?
Ages 30 to 62 years
Conditions the study is for
ATRIAL FIBRILLATION
What is being tested?
Rivaroxaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,238 participants
Where
41 sitesCanada
Study dates
Mar 2015to 18 May 2024
Phase
Phase 3
Are there results?
None posted in the registry

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 30 to 62 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Age at consent ≥30 to ≤62 years;
  • Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing or any device (i.e. routine 12-lead electrocardiogram, Holter monitor [continuous ECG recording] rhythm strip, intracardiac electrogram, or pacemaker or implantable cardiac defibrillator interrogation of at least 30 s, transcutaneous monitoring or other) in the last 2 years;
  • Low risk of stroke as defined by the absence of all of the following:
  • Prior stroke or Transient Ischemic Attack, ii. Hypertension, iii. Diabetes mellitus, iv. Congestive heart failure (New York Heart Association class II or higher at the time of enrolment or a known left ventricular ejection fraction <35%);
  • Signed informed consent
  • For entry into the study, none of the following criteria MUST be met

Who cannot join

  • Known diagnosis of dementia;
  • MMSE score <25;
  • Valvular AF [mechanical heart valve, moderate to severe mitral stenosis (rheumatic or non rheumatic), or hypertrophic cardiomyopathy];
  • Other indication for antiplatelet therapy or anticoagulation;
  • History of GI bleeding;
  • Conditions associated with an increased risk of bleeding described as follows:
Show all 25Show fewer
  • Major surgery within the previous month;
  • Planned surgery or intervention within the next 3 months;
  • History of intracranial, intraocular, spinal, retroperitoneal or a traumatic intra-articular bleeding;
  • Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days;
  • Haemorrhagic disorder or bleeding diathesis;
  • Fibrinolytic agents within 48 hours of study entry;
  • Recent malignancy or radiation therapy (within 6 months from the time of enrolment) and not expected to survive 3 years;
  • Reversible cause of AF (e.g. cardiac surgery, pulmonary embolism, untreated hyperthyroidism);
  • Absence of recurrence of AF 3 months after AF ablation;
  • Severe renal impairment (creatinine clearance 30 mL/min or less);
  • Active infective endocarditis;
  • Active liver disease (e.g. acute clinical hepatitis, chronic active hepatitis, cirrhosis), or Alanine Transaminase (ALT) >3 times the upper limit of normal;
  • Women who are pregnant or of childbearing potential not using a medically acceptable form of contraception throughout the study;
  • Women who are breastfeeding;
  • Anemia or thrombocytopenia (according to the normal range values of the local laboratory);
  • Participation in another study involving an investigational drug (under development) at the same time or within 30 days of randomization;
  • Subjects considered unreliable, or having a life expectancy of less than 3 years or having any condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g. drug addiction, alcohol abuse);
  • History of allergic reaction to rivaroxaban.
  • History of allergic reaction, in the absence of desensitization to acetylsalicylic acid in patients with vascular disease.

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

Canada41 sites

  • Office of Dr. TunZan Maung, MD

    Abbotsford British Columbia, British Columbia, V5Z 1M9

  • Viacar Recherche Clinique Inc.

    Brossard, Quebec

  • CardiAi Inc.

    Calgary, Alberta

  • Libin Cardiovascular Institute of Alberta

    Calgary, Alberta

  • Cambridge Cardiac Care Center

    Cambridge, Ontario

  • Vizel Cardiac Research

    Cambridge, Ontario

  • CIUSSS du Saguenay-Lac-Saint-Jean

    Chicoutimi, Quebec

  • University of Alberta

    Edmonton, Alberta

  • CIUSSS de l'Estrie-CHUS-Centre Haute-Yamaska (Hopital de Granby)

    Granby, Quebec

  • CISSSMC-Hopital Charles-Lemoyne

    Greenfield Park, Quebec

  • Viacar Recherche Clinique Inc.

    Greenfield Park, Quebec

  • QEll Health Sciences Center-Halifax Infirmary

    Halifax, Nova Scotia

  • Hamilton Health Sciences - General Site

    Hamilton, Ontario

  • McMaster University

    Hamilton, Ontario

  • Cardiology Clinic

    Kitchener, Ontario

  • St. Mary's general Hospital

    Kitchener, Ontario

  • Hopital de la Cite-de-la-Sante

    Laval, Quebec

  • Clinique Cardiologie de Levis

    Lévis, Quebec

  • Western University - London Health Sciences Centre

    London, Onatrio

  • One Heart Care

    Mississauga, Ontario

  • Dr. Georges-L - Dumont University Hospital Center

    Moncton, New Brunswick

  • Montreal Heart Institute

    Montreal, Quebec, H1T1C8

  • CHUM

    Montreal, Quebec

  • Hopital du Sacre Coeur de Montreal

    Montreal, Quebec

  • McGill University Health Center

    Montreal, Quebec

  • Montreal Heart Institute

    Montreal, Quebec

  • PACE (Partners in Advanced Cardiac Evaluation)

    Newmarket, Onatrio

  • North Shore Heart Center

    North Vancouver, British Columbia

  • Oakville Cardiovascular Research LP

    Oakville, Onatrio

  • University of Ottawa Heart Institute

    Ottawa, Ontario

  • CHU de Quebec-Universite Laval/Hotel Dieu de Quebec

    Québec

  • Institut Universitaire de Cardiologie et de Pneumologie de Quebec

    Québec

  • CISSS BSL-Hopital de Rimouski

    Rimouski, Quebec

  • CISSS des Laurentides-Unite de recherche clinique

    Saint-Jérôme, Quebec

  • CIUSSS de l'Estrie-CHUS

    Sherbrooke, Quebec

  • CISSS de Lanaudiere-Hopital Pierre-Le Gardeur

    Terrebonne, Quebec

  • St. Michael's Hospital

    Toronto, Ontario

  • CIUSSS MCQ CHAUR- Centre Hospitalier regional de Trois-Rivieres

    Trois-Rivières, Quebec

  • Vancouver General Hospital/UBC

    Vancouver, British Columbia

  • Cardio 1

    Winnipeg, Manitoba

  • St. Boniface Hospital

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in AF (BRAIN-AF)

This is a prospective, multicenter, randomized, double-blinded clinical trial exploring the efficacy and safety of rivaroxaban as compared to standard of care in reducing stroke, transient ischemic attack (TIA) and neurocognitive decline, in subjects with non-valvular AF and with low risk of stroke.

Read the detailed description

Subjects who qualify will be approached and those consenting will be enrolled to undergo a baseline evaluation. Subjects without a clinical diagnosis of dementia and with a Mini Mental State Examination score (MMSE) score ≥ 25 will undergo neurocognitive assessment (MoCA), psychosocial and QoL assessment before randomization.

Subjects will undergo regular visits (in-clinic, and/or by phone, or video conferencing) every 6 months during the treatment period. Subjects will take either rivaroxaban 15 mg or standard of care.

An independent clinical event committee will classify all endpoint events. An independent Data Safety Monitoring Committee (DSMC) was established to monitor the progress of the study and assure the safety of subjects enrolled in the trial.

Being tested
Rivaroxaban, standard of care
Keywords
Atrial Fibrillation, Stroke, Neurocognitive decline, Rivaroxaban, Acetylsalicylic acid, Anticoagulation, Montreal Cognitive Assesssment (MoCA), Mini-Mental State Examination (MMSE)
Medical subject headings
Atrial Fibrillation, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RivaroxabanDrug

    Also called Xarelto

    15 mg

  • standard of careOther

Study groups in NCT02387229
Study groupRoleWhat they receive
RivaroxabanActive comparatorRivaroxaban 15 mg, orally, once daily, preferably at the same time of the day throughout the study.
Receives: Drug: Rivaroxaban
standard of careActive comparatorstandard of care
Receives: Other: standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite endpoint of stroke, TIA and neurocognitive decline. Neurocognitive decline is defined by a decrease in the MoCA score greater than or equal to 2 at any follow-up visit from baseline.

    From date of randomization until the date of first documented occurrence of any component of the composite, assessed up to the end of the study

    Measured: estimated up to 84 months

Secondary outcomes (4)

  1. Death (total and cardiovascular)

    From date of randomization until the date of first documented death (total and cardiovascular), assessed up to the end of the study

    Measured: estimated up to 84 months

  2. Composite including stroke/transient ischemic attack (TIA) and systemic embolic events

    From date of randomization until the date of first documented composite including stroke/transient ischemic attack (TIA) and systemic embolic events, assessed up to the end of the study

    Measured: estimated up to 84 months

  3. Neurocognitive decline

    From date of randomization until the date of first documented neurocognitive decline, assessed up to the end of the study. First occurrence of decrease in MoCA score ≥2 at any follow up visit from baseline.

    Measured: estimated up to 84 months

  4. Hospitalization for cardiovascular (myocardial infarction, heart failure, AF, stroke or unstable angina or other cardiovascular events) or bleeding event

    From date of randomization until the date of first documented hospitalization for cardiovascular (myocardial infarction, heart failure, AF, stroke, other cardiovascular events or bleeding event, assessed up to the end of the study. Hospitalization is defined as an admission to an inpatient unit or a visit to an emergency department that results in at least a 24 hour stay

    Measured: estimated up to 84 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2015 (estimated)
  2. Study startMar 2015
  3. Primary completion18 May 2024
  4. Study completion18 May 2024

Why it stopped: Consensus BRAIN-AF Executive Steering Committee to terminate.

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,238 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02387229
Sponsor's protocol ID
BRAIN-001
Acronym
BRAIN-AF
Status last verified
Jun 2025
First submitted
26 Feb 2015
Last updated
15 Jun 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Rivard L, Khairy P, Talajic M, Tardif JC, Healey JS, Black SE, Andrade JG, Field TS, Nault I, Bherer L, Massoud F, Nattel S, Lanthier S, Racine N, Roux JF, Greiss I, Macle L, Guerra PG, Tadros R, Mayrand H, Gosselin G, Conen D, Bocti C, Chayer C, Deschaintre Y, Sandhu RK, Manlucu J, Khaykin Y, Verma A, Mondesert B, Dyrda K, Cadrin-Tourigny J, Thibault B, Raymond-Paquin A, Aguilar M, Brouillette J, Roussin A, Robillard A, Tremblay-Gravel M, David LP, Cossette M, Parkash R, Guertin MC, Roy D; BRAIN-AF investigators. Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial. Nat Med. 2026 Jan;32(1):297-305. doi: 10.1038/s41591-025-04101-y. Epub 2026 Jan 7.

    PubMed 41501492

  • Rivard L, Khairy P, Talajic M, Tardif JC, Nattel S, Bherer L, Black S, Healey J, Lanthier S, Andrade J, Massoud F, Nault I, Guertin MC, Dorian P, Kouz S, Essebag V, Ellenbogen KA, Wyse G, Racine N, Macle L, Mondesert B, Dyrda K, Tadros R, Guerra P, Thibault B, Cadrin-Tourigny J, Dubuc M, Roux JF, Mayrand H, Greiss I, Roy D. Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF): Methods and Design. Can J Cardiol. 2019 Aug;35(8):1069-1077. doi: 10.1016/j.cjca.2019.04.022. Epub 2019 May 7.

    PubMed 31376908

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rivaroxaban in people with ATRIAL FIBRILLATION, run by Montreal Heart Institute at 41 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 6 inclusion and 25 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: stopped early, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Consensus BRAIN-AF Executive Steering Committee to terminate.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite endpoint of stroke, TIA and neurocognitive decline. Neurocognitive decline is defined by a decrease in the MoCA score greater than or equal to 2 at any follow-up visit from baseline. (time frame: estimated up to 84 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02387229, which also lists 2 linked publications.

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 15 Jun 2025.

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