NCT02387229

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,238

participants targeted

Target at P75+ for phase_3 atrial-fibrillation

Timeline
Completed

Started Mar 2015

Longer than P75 for phase_3 atrial-fibrillation

Geographic Reach
1 country

41 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 26, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 12, 2015

Completed
9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 18, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2024

Completed
Last Updated

June 15, 2025

Status Verified

June 1, 2025

Enrollment Period

9.2 years

First QC Date

February 26, 2015

Last Update Submit

June 11, 2025

Conditions

Keywords

Atrial FibrillationStrokeNeurocognitive declineRivaroxabanAcetylsalicylic acidAnticoagulationMontreal Cognitive Assesssment (MoCA)Mini-Mental State Examination (MMSE)

Outcome Measures

Primary Outcomes (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.

    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 Outcomes (4)

  • Death (total and cardiovascular)

    estimated up to 84 months

  • Composite including stroke/transient ischemic attack (TIA) and systemic embolic events

    estimated up to 84 months

  • Neurocognitive decline

    estimated up to 84 months

  • Hospitalization for cardiovascular (myocardial infarction, heart failure, AF, stroke or unstable angina or other cardiovascular events) or bleeding event

    estimated up to 84 months

Other Outcomes (1)

  • Major clinical bleeding event

    estimated up to 84 months

Study Arms (2)

Rivaroxaban

ACTIVE COMPARATOR

Rivaroxaban 15 mg, orally, once daily, preferably at the same time of the day throughout the study.

Drug: Rivaroxaban

standard of care

ACTIVE COMPARATOR

standard of care

Other: standard of care

Interventions

15 mg

Also known as: Xarelto
Rivaroxaban
standard of care

Eligibility Criteria

Age30 Years - 62 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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;
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (41)

CardiAi Inc.

Calgary, Alberta, Canada

Location

Libin Cardiovascular Institute of Alberta

Calgary, Alberta, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Office of Dr. TunZan Maung, MD

Abbotsford, British Columbia, V5Z 1M9, Canada

Location

North Shore Heart Center

North Vancouver, British Columbia, Canada

Location

Vancouver General Hospital/UBC

Vancouver, British Columbia, Canada

Location

Cardio 1

Winnipeg, Manitoba, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, Canada

Location

Dr. Georges-L - Dumont University Hospital Center

Moncton, New Brunswick, Canada

Location

QEll Health Sciences Center-Halifax Infirmary

Halifax, Nova Scotia, Canada

Location

Western University - London Health Sciences Centre

London, Onatrio, Canada

Location

PACE (Partners in Advanced Cardiac Evaluation)

Newmarket, Onatrio, Canada

Location

Oakville Cardiovascular Research LP

Oakville, Onatrio, Canada

Location

Cambridge Cardiac Care Center

Cambridge, Ontario, Canada

Location

Vizel Cardiac Research

Cambridge, Ontario, Canada

Location

Hamilton Health Sciences - General Site

Hamilton, Ontario, Canada

Location

McMaster University

Hamilton, Ontario, Canada

Location

Cardiology Clinic

Kitchener, Ontario, Canada

Location

St. Mary's general Hospital

Kitchener, Ontario, Canada

Location

One Heart Care

Mississauga, Ontario, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Viacar Recherche Clinique Inc.

Brossard, Quebec, Canada

Location

CIUSSS du Saguenay-Lac-Saint-Jean

Chicoutimi, Quebec, Canada

Location

CIUSSS de l'Estrie-CHUS-Centre Haute-Yamaska (Hopital de Granby)

Granby, Quebec, Canada

Location

CISSSMC-Hopital Charles-Lemoyne

Greenfield Park, Quebec, Canada

Location

Viacar Recherche Clinique Inc.

Greenfield Park, Quebec, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

Location

Clinique Cardiologie de Levis

Lévis, Quebec, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T1C8, Canada

Location

CHUM

Montreal, Quebec, Canada

Location

Hopital du Sacre Coeur de Montreal

Montreal, Quebec, Canada

Location

McGill University Health Center

Montreal, Quebec, Canada

Location

Montreal Heart Institute

Montreal, Quebec, Canada

Location

CISSS BSL-Hopital de Rimouski

Rimouski, Quebec, Canada

Location

CISSS des Laurentides-Unite de recherche clinique

Saint-Jérôme, Quebec, Canada

Location

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, Canada

Location

CISSS de Lanaudiere-Hopital Pierre-Le Gardeur

Terrebonne, Quebec, Canada

Location

CIUSSS MCQ CHAUR- Centre Hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Location

CHU de Quebec-Universite Laval/Hotel Dieu de Quebec

Québec, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Canada

Location

Related Publications (2)

  • Rivard L, Khairy P, Talajic M, Tardif JC, Healey JS, Black SE, Andrade JG, Field TS, Nault I, Bherer L, Massoud F, Nattel S, Lanthier S, Racine N, Roux JF, Greiss I, Macle L, Guerra PG, Tadros R, Mayrand H, Gosselin G, Conen D, Bocti C, Chayer C, Deschaintre Y, Sandhu RK, Manlucu J, Khaykin Y, Verma A, Mondesert B, Dyrda K, Cadrin-Tourigny J, Thibault B, Raymond-Paquin A, Aguilar M, Brouillette J, Roussin A, Robillard A, Tremblay-Gravel M, David LP, Cossette M, Parkash R, Guertin MC, Roy D; BRAIN-AF investigators; Pandey AS, Pichette F, Barrero M, Kus T, Lemieux A, Gaudreault V, Marzban P, Wong J, Sit PL, Laflamme D, Fowlis R, Quadros K, Kapoor A, Jolly US, Wilton S, Azzari FA, Dorian P, Deslongchamps F, Pesant Y, Vizel S, Maung T, Heffernan M, Nery P, Curnew G, Bourgeois S, Essebag V, Kouz S, Cormier L, Vyselaar J, Chehayeb R, Khoo C, Gupta A, Bessoudo R, Bhargava R, Sandrin F, Schram G, St-Maurice F, Tsui W, Liang W. Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial. Nat Med. 2026 Jan 7. doi: 10.1038/s41591-025-04101-y. Online ahead of print.

  • 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.

MeSH Terms

Conditions

Atrial FibrillationStroke

Interventions

RivaroxabanStandard of Care

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

ThiophenesSulfur CompoundsOrganic ChemicalsMorpholinesOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsQuality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Lena Rivard, MD

    Montreal Heart Institute

    PRINCIPAL INVESTIGATOR
  • Sophie Tanguay, M.Sc.

    Montreal health Innovations Coordinating Centre

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 26, 2015

First Posted

March 12, 2015

Study Start

March 1, 2015

Primary Completion

May 18, 2024

Study Completion

May 18, 2024

Last Updated

June 15, 2025

Record last verified: 2025-06

Locations