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

Recruiting

Phase 3 Results N/A

Update History

10 Feb '18
Trial name was updated.
New
Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in AF
The description was updated.
New
Subjects who qualify will be approached and those consenting will be enrolled to undergo a baseline evaluation including the modified mini mental state test (3MS). 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 (between a minimum of 3 and 6.5 years depending on the length of the recruitment), subjects will receive study medications as fixed doses. During the follow-up period, subjects will visit the clinic every 6 months up to a maximum of 78 months. Subjects will take either rivaroxaban 15 mg with matching acetylsalicylic acid - placebo or acetylsalicylic acid 100 mg with matching rivaroxaban-placebo orally, once daily, preferably at the same time of the day throughout the study. 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.
Old
Subjects who qualify will be approached and those consenting will be enrolled to undergo a baseline evaluation including the modified mini mental state test (3MS). 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 (between a minimum of 3.5 and 6.5 years depending on the length of the recruitment), subjects will receive study medications as fixed doses. During the follow-up period, subjects will visit the clinic every 6 months up to a maximum of 78 months. Subjects will take either rivaroxaban 15 mg with matching acetylsalicylic acid - placebo or acetylsalicylic acid 100 mg with matching rivaroxaban-placebo orally, once daily, preferably at the same time of the day throughout the study. 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.
The gender criteria for eligibility was updated to "All."
The eligibility criteria were updated.
New
For entry into the study, the following criteria must be met: Inclusion Criteria: - Age at consent ≥30 to ≤61 years - Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing (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) within the prior 18 months - 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; - 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 randomisation; - 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.
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For entry into the study, the following criteria MUST be met: Inclusion Criteria: - Age at consent ≥30 to ≤60 years - Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing (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) within the prior 12 months - 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; - 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 breast feeding; - Anemia or thrombocytopenia (according to the normal range values of the local laboratory); - Investigational drug received in the past 30 days; - 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.
12 Dec '15
The eligibility criteria were updated.
New
For entry into the study, the following criteria MUST be met: Inclusion Criteria: - Age at consent ≥30 to ≤60 years - Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing (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) within the prior 12 months - 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; - 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 breast feeding; - Anemia or thrombocytopenia (according to the normal range values of the local laboratory); - Investigational drug received in the past 30 days; - 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.
Old
For entry into the study, the following criteria MUST be met: Inclusion Criteria: - Age at consent ≥30 to ≤60 years - Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing (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) within the prior 12 months - 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; - 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 breast feeding; - Anemia or thrombocytopenia (according to the normal range values of the local laboratory); - Investigational drug received in the past 30 days; - 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.
7 May '15
A location was updated in Montreal.
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The overall status was updated to "Recruiting" at Montreal Heart Institute.