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

NCT ID: NCT02387229

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1238 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2024-05-18

Brief 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.

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.

Conditions

ATRIAL FIBRILLATION

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Rivaroxaban

Rivaroxaban 15 mg, orally, once daily, preferably at the same time of the day throughout the study.

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

15 mg

standard of care

standard of care

Group Type: ACTIVE_COMPARATOR

standard of care

Intervention Type: OTHER

Interventions

Rivaroxaban

15 mg

Intervention Type: DRUG

standard of care

Intervention Type: OTHER

Other Intervention Names

Xarelto

Eligibility Criteria

Inclusion Criteria

• 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:

i. 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

Exclusion Criteria

• 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:

1. Major surgery within the previous month;

2. Planned surgery or intervention within the next 3 months;

3. History of intracranial, intraocular, spinal, retroperitoneal or a traumatic intra-articular bleeding;

4. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days;

5. Haemorrhagic disorder or bleeding diathesis;

6. Fibrinolytic agents within 48 hours of study entry;

7. 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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 62 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Stroke Prevention Intervention Network

OTHER

Sponsor Role: collaborator

The Montreal Health Innovations Coordinating Center (MHICC)

OTHER

Sponsor Role: collaborator

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

INDUSTRY

Sponsor Role: collaborator

Montreal Heart Institute Foundation

UNKNOWN

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Hewitt Foundation

UNKNOWN

Sponsor Role: collaborator

Montreal Heart Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lena Rivard, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute

Sophie Tanguay, M.Sc.

Role: STUDY_DIRECTOR

Montreal health Innovations Coordinating Centre

Locations

CardiAi Inc.

Calgary, Alberta, Canada

Libin Cardiovascular Institute of Alberta

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Office of Dr. TunZan Maung, MD

Abbotsford, British Columbia, Canada

North Shore Heart Center

North Vancouver, British Columbia, Canada

Vancouver General Hospital/UBC

Vancouver, British Columbia, Canada

Cardio 1

Winnipeg, Manitoba, Canada

St. Boniface Hospital

Winnipeg, Manitoba, Canada

Dr. Georges-L - Dumont University Hospital Center

Moncton, New Brunswick, Canada

QEll Health Sciences Center-Halifax Infirmary

Halifax, Nova Scotia, Canada

Western University - London Health Sciences Centre

London, Onatrio, Canada

PACE (Partners in Advanced Cardiac Evaluation)

Newmarket, Onatrio, Canada

Oakville Cardiovascular Research LP

Oakville, Onatrio, Canada

Cambridge Cardiac Care Center

Cambridge, Ontario, Canada

Vizel Cardiac Research

Cambridge, Ontario, Canada

Hamilton Health Sciences - General Site

Hamilton, Ontario, Canada

McMaster University

Hamilton, Ontario, Canada

Cardiology Clinic

Kitchener, Ontario, Canada

St. Mary's general Hospital

Kitchener, Ontario, Canada

One Heart Care

Mississauga, Ontario, Canada

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Viacar Recherche Clinique Inc.

Brossard, Quebec, Canada

CIUSSS du Saguenay-Lac-Saint-Jean

Chicoutimi, Quebec, Canada

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

Granby, Quebec, Canada

CISSSMC-Hopital Charles-Lemoyne

Greenfield Park, Quebec, Canada

Viacar Recherche Clinique Inc.

Greenfield Park, Quebec, Canada

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

Clinique Cardiologie de Levis

Lévis, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

CHUM

Montreal, Quebec, Canada

Hopital du Sacre Coeur de Montreal

Montreal, Quebec, Canada

McGill University Health Center

Montreal, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

CISSS BSL-Hopital de Rimouski

Rimouski, Quebec, Canada

CISSS des Laurentides-Unite de recherche clinique

Saint-Jérôme, Quebec, Canada

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, Canada

CISSS de Lanaudiere-Hopital Pierre-Le Gardeur

Terrebonne, Quebec, Canada

CIUSSS MCQ CHAUR- Centre Hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

CHU de Quebec-Universite Laval/Hotel Dieu de Quebec

Québec, , Canada

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, , Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 31376908 (View on PubMed)

Other Identifiers

BRAIN-001

Identifier Type: -

Identifier Source: org_study_id