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

• ClinicalTrials.gov Identifier: NCT02387229
• Recruitment Status: Recruiting
• First Posted: March 12, 2015
• Last Update Posted: December 22, 2022
• Sponsor: Montreal Heart Institute
• Collaborators: Canadian Stroke Prevention Intervention Network; The Montreal Health Innovations Coordinating Center (MHICC); Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma; Montreal Heart Institute Foundation; Canadian Institutes of Health Research (CIHR); Hewitt Foundation
• Information provided by (Responsible Party): Montreal Heart Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
ATRIAL FIBRILLATION	Drug: Rivaroxaban; Other: standard of care	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1424 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in AF (BRAIN-AF)
• Actual Study Start Date: March 2015
• Estimated Primary Completion Date: December 2026
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Rivaroxaban; Rivaroxaban 15 mg, orally, once daily, preferably at the same time of the day throughout the study.	Drug: Rivaroxaban; 15 mg; Other Name: Xarelto
Active Comparator: standard of care; standard of care	Other: standard of care

Outcome Measures

Primary Outcome Measures :

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. [ Time Frame: estimated up to 84 months ]
   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

Secondary Outcome Measures :

1. Death (total and cardiovascular) [ Time Frame: estimated up to 84 months ]
   From date of randomization until the date of first documented death (total and cardiovascular), assessed up to the end of the study
2. Composite including stroke/transient ischemic attack (TIA) and systemic embolic events [ Time Frame: estimated up to 84 months ]
   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
3. Neurocognitive decline [ Time Frame: estimated up to 84 months ]
   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.
4. Hospitalization for cardiovascular (myocardial infarction, heart failure, AF, stroke or unstable angina or other cardiovascular events) or bleeding event [ Time Frame: estimated up to 84 months ]
   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

Other Outcome Measures:

1. Major clinical bleeding event [ Time Frame: estimated up to 84 months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 62 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Isabelle Robert, M.Sc; 514-461-1300 ext 2037; Isabelle.Robert@mhicc.org

Locations

Canada, Quebec

Montreal Heart Institute; Recruiting

Montreal, Quebec, Canada, H1T1C8

Contact: Lena Rivard, MD (514) 376-3330 ext 2120 lena.rivard@umontreal.ca

Principal Investigator: Lena Rivard, MD

Sub-Investigator: Katia Dyrda, MD

Sub-Investigator: Denis Roy, MD

Sub-Investigator: Mario Talajic, MD

Sub-Investigator: Paul Khairy, MD

Sub-Investigator: Bernard Thibault, MD

Sub-Investigator: Marc Dubuc, MD

Sub-Investigator: Peter Guerra, MD

Sub-Investigator: Laurent Macle, MD

Sub-Investigator: Jason Andrade, MD

Sub-Investigator: Blandine Mondésert, MD

Sponsors and Collaborators

Montreal Heart Institute

Canadian Stroke Prevention Intervention Network

The Montreal Health Innovations Coordinating Center (MHICC)

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Montreal Heart Institute Foundation

Canadian Institutes of Health Research (CIHR)

Hewitt Foundation

Investigators

• Principal Investigator: Lena Rivard, MD; Montreal Heart Institute
• Study Director: Sophie Tanguay, M.Sc.; Montreal health Innovations Coordinating Centre

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Montreal Heart Institute
• ClinicalTrials.gov Identifier: NCT02387229
• Other Study ID Numbers: BRAIN-001
• First Posted: March 12, 2015
• Last Update Posted: December 22, 2022
• Last Verified: October 2022

Keywords provided by Montreal Heart Institute:

Atrial Fibrillation; Stroke; Neurocognitive decline; Rivaroxaban; Acetylsalicylic acid; Anticoagulation; Montreal Cognitive Assesssment (MoCA); Mini-Mental State Examination (MMSE)

Additional relevant MeSH terms:

Ischemic Stroke; Atrial Fibrillation; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Rivaroxaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants