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

ATRIAL FIBRILLATION Clinical Trial

— BRAIN-AF  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02387229
• Other study ID #: BRAIN-001
• Status: Terminated
• Phase: Phase 3
• Start date: March 2015
• Est. completion date: December 2023

Study information

• Verified date: December 2023
• Source: Montreal Heart Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1238
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 62 Years

Eligibility

For entry into the study, the following criteria must be met:

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.

Related Conditions & MeSH terms

• ATRIAL FIBRILLATION
• Ischemic Stroke

Intervention

Drug:
• Rivaroxaban
15 mg

Other:
• standard of care

Locations

Country	Name	City	State
Canada	Office of Dr. TunZan Maung, MD	Abbotsford	British Columbia
Canada	Viacar Recherche Clinique Inc.	Brossard	Quebec
Canada	CardiAi Inc.	Calgary	Alberta
Canada	Libin Cardiovascular Institute of Alberta	Calgary	Alberta
Canada	Cambridge Cardiac Care Center	Cambridge	Ontario
Canada	Vizel Cardiac Research	Cambridge	Ontario
Canada	CIUSSS du Saguenay-Lac-Saint-Jean	Chicoutimi	Quebec
Canada	University of Alberta	Edmonton	Alberta
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	QEll Health Sciences Center-Halifax Infirmary	Halifax	Nova Scotia
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	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	Clinique Cardiologie de Levis	Levis	Quebec
Canada	Western University - London Health Sciences Centre	London	Onatrio
Canada	One Heart Care	Mississauga	Ontario
Canada	Dr. Georges-L - Dumont University Hospital Center	Moncton	New Brunswick
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	Montreal Heart Institute	Montreal	Quebec
Canada	PACE (Partners in Advanced Cardiac Evaluation)	Newmarket	Onatrio
Canada	North Shore Heart Center	North Vancouver	British Columbia
Canada	Oakville Cardiovascular Research LP	Oakville	Onatrio
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	CHU de Quebec-Universite Laval/Hotel Dieu de Quebec	Quebec
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec
Canada	CISSS BSL-Hopital de Rimouski	Rimouski	Quebec
Canada	CISSS des Laurentides-Unite de recherche clinique	Saint-Jerome	Quebec
Canada	CIUSSS de l'Estrie-CHUS	Sherbrooke	Quebec
Canada	CISSS de Lanaudiere-Hopital Pierre-Le Gardeur	Terrebonne	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	CIUSSS MCQ CHAUR- Centre Hospitalier regional de Trois-Rivieres	Trois-Rivières	Quebec
Canada	Vancouver General Hospital/UBC	Vancouver	British Columbia
Canada	Cardio 1	Winnipeg	Manitoba
Canada	St. Boniface Hospital	Winnipeg	Manitoba

Sponsors (7)

Lead Sponsor	Collaborator
Montreal Heart Institute	Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma, Canadian Institutes of Health Research (CIHR), Canadian Stroke Prevention Intervention Network, Hewitt Foundation, Montreal Heart Institute Foundation, The Montreal Health Innovations Coordinating Center (MHICC)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Major clinical bleeding event	From date of randomization until the date of first documented major clinical bleeding event, assessed up to the end of the study. First occurrence of bleeding events consider as major or requiring hospitalization. Bleeding will be defined in accordance with the International Society on Thrombosis and Haemostasis (ISTH).	estimated up to 84 months
Primary	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	estimated up to 84 months
Secondary	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	estimated up to 84 months
Secondary	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	estimated up to 84 months
Secondary	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.	estimated up to 84 months
Secondary	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	estimated up to 84 months