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

Sponsor

Montreal Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT02387229

Collaborator

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

2,180

Enrollment

Location

Arms

107.1

Anticipated Duration (Months)

20.4

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

2180 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 :

Mar 1, 2015

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

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 Names: Xarelto
Active Comparator: standard of care standard of care	Other: standard of care

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 Names:

Xarelto

Active Comparator: standard of care

standard of care

Other: standard of care

Outcome Measures

Primary Outcome Measures

Composite endpoint of stroke, TIA and neurocognitive decline. Neurocognitive decline is defined by a decrease in the MoCA score greater than or equal to 3 at any follow-up visit from baseline. [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

Death (total and cardiovascular) [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
Composite including stroke/transient ischemic attack (TIA) and systemic embolic events [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
Neurocognitive decline [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.
Hospitalization for cardiovascular (myocardial infarction, heart failure, AF, stroke or unstable angina or other cardiovascular events) or bleeding event [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

Major clinical bleeding event [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

Criteria

Ages Eligible for Study:

30 Years to 62 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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:

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.