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

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ClinicalTrials.gov Identifier: NCT02387229
Recruitment Status : Recruiting
First Posted : March 12, 2015
Last Update Posted : August 9, 2019
Sponsor:
Collaborators:
Canadian Stroke Prevention Intervention Network
The Montreal Health Innovations Coordinating Center (MHICC)
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Montreal Heart Institute Foundation
Information provided by (Responsible Party):
Montreal Heart Institute

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.

During the follow-up period or double-blind treatment period, subjects will receive study medications as fixed doses. During the follow-up period, subjects will visit the clinic every 6 months. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3250 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 : February 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban

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



Primary Outcome Measures :
  1. Composite endpoint of stroke, TIA and neurocognitive decline [ 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 ≥3 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 (routine 12-lead electrocardiogram (ECG)), 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 written 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 (Clinically significant (severe or moderate) rheumatic mitral stenosis, mechanical or bioprosthetic heart valve, or mitral valve repair) 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);
  • Plan to perform pulmonary vein ablation or surgery for treatment of AF;
  • 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);
  • Known diagnosis of major depression within the past year defined as:

    1. Subject who has/had a clinical diagnosis made by a psychiatrist through medical evaluation;
    2. Subject who had required hospitalization for the management of their major depression;
    3. Subject has had a suicide attempt.
  • History of allergic reaction to rivaroxaban.
  • History of allergic reaction, in the absence of desensitization to acetylsalicylic acid in patients with vascular disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02387229


Contacts
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Contact: Isabelle Robert, M.Sc 514-461-1300 ext 2037 Isabelle.Robert@mhicc.org
Contact: Brigitte DeChamisso, D.E.A 514-461-1300 ext 4057 brigitte.dechamisso@mhicc.org

Locations
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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
Investigators
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Principal Investigator: Lena Rivard, MD Montreal Heart Institute

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Responsible Party: Montreal Heart Institute
ClinicalTrials.gov Identifier: NCT02387229     History of Changes
Other Study ID Numbers: BRAIN-001
First Posted: March 12, 2015    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Keywords provided by Montreal Heart Institute:
Atrial Fibrillation
Stroke
Neurocognitive decline
Rivaroxaban
Acetylsalicylic acid
Anticoagulation
Additional relevant MeSH terms:
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Atrial Fibrillation
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