The Fourth Left Atrial Appendage Occlusion Study
- Conditions
- Atrial FibrillationStroke, IschemicSystemic Embolism
- Interventions
- Device: WATCHMAN device
- Registration Number
- NCT05963698
- Lead Sponsor
- Hamilton Health Sciences Corporation
- Brief Summary
LAAOS-4 aims to determine if catheter-based endovascular left atrial appendage occlusion prevents ischemic stroke or systemic embolism in participants with atrial fibrillation, who remain at high risk of stroke, despite receiving ongoing treatment with oral anticoagulation.
- Detailed Description
LAAOS-4 is a multicentre, prospective, open-label, randomized controlled trial with blinded assessment of endpoints (PROBE) to determine if catheter-based endovascular left atrial appendage occlusion prevents ischemic stroke or systemic embolism in participants with atrial fibrillation, who remain at high risk of stroke, despite receiving ongoing treatment with oral anticoagulation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 4000
- (a) Persistent or permanent atrial fibrillation OR (b) Paroxysmal atrial fibrillation in participants with a history of ischemic stroke or systemic embolism
- Increased risk of stroke, defined as a CHA2DS2-VASc stroke risk score of ≥ 4. [Note: the acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female).]
- Treatment with oral anticoagulants (Vitamin K agonist or factor Xa inhibitor) for at least 90 days prior to enrollment, AND no documented plan to discontinue treatment with oral anticoagulants for the expected duration of the trial.
- Age < 18 years
- Current left atrial appendage thrombus
- Prior left atrial appendage occlusion or removal (surgical or percutaneous)
- Prior percutaneous atrial septal defect or patent foramen ovale closure
- Prior atrial fibrillation ablation unless evidence of recurrent qualifying atrial fibrillation present at least 30 days following ablation
- Planned atrial fibrillation ablation within 90 days of enrollment
- Individuals being treated with direct thrombin inhibitors
- Women of childbearing potential unless they agree to employ effective birth control methods throughout the study
- Anticipated life-expectancy of < 2 years
- Patient unable or willing to give informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description WATCHMAN device WATCHMAN device Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
- Primary Outcome Measures
Name Time Method Ischemic stroke or systemic embolism The study duration is event-driven. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). The primary efficacy variable is the time from randomization to first occurrence of any of the components of the composite outcome (adjudicated) over the duration of follow-up, including:
* Ischemic stroke (Strokes of undetermined etiology will be treated as ischemic stroke)
* Systemic embolism
- Secondary Outcome Measures
Name Time Method Montreal Cognitive Assessment (MoCA) Score Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Proportion of participants with a decrease of two or more points on the MoCA score at either year 2 or end of study
All-cause mortality Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Time from randomization to all-cause mortality
All-cause stroke or systemic embolism Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Secondary efficacy outcomes will be evaluated in a hierarchical fashion only when the primary outcome meets statistical significance in the specified order:
Time from randomization to first occurrence of all-cause stroke or systemic embolismNew disabling ischemic strokes Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Time from randomization to first occurrence of disabling ischemic strokes with modified Rankin Score (mRS) \>2, measured at 90 days post-stroke
All-cause stroke, systemic embolism, or transient ischemic attack (TIA) Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Time from randomization to first occurrence of all-cause stroke, systemic embolism or transient ischemic attack (TIA)
Cardiovascular mortality Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years). Time from randomization to cardiovascular mortality
Trial Locations
- Locations (53)
St. Vincent's Health System
🇺🇸Jacksonville, Florida, United States
Kootenai Health Inc.
🇺🇸Coeur d'Alene, Idaho, United States
Affinity Hospital dba Grandview Medical Center
🇺🇸Birmingham, Alabama, United States
Arrhythmia Research Group
🇺🇸Jonesboro, Arkansas, United States
Memorial Health Services
🇺🇸Fountain Valley, California, United States
Sutter Valley Hospitals dba Sutter Institute for Medical Research
🇺🇸Sacramento, California, United States
Northwestern University
🇺🇸Evanston, Illinois, United States
Community Health Network Inc.
🇺🇸Indianapolis, Indiana, United States
MercyOne Iowa Heart Center
🇺🇸West Des Moines, Iowa, United States
Babtist Health Lexington
🇺🇸Lexington, Kentucky, United States
Lahey Clinic Inc.
🇺🇸Burlington, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
The Feinstein Institutes for Medical Research
🇺🇸Manhasset, New York, United States
NYU Grossman School of Medicine
🇺🇸New York, New York, United States
Cornell University for and on behalf of its Joan & Sanford I. Weill Medical College and The New York Presbyterian Hospital
🇺🇸New York, New York, United States
Mission Hospital HCA
🇺🇸Asheville, North Carolina, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
TriHealth Inc.
🇺🇸Cincinnati, Ohio, United States
Texas Cardiac Arrhythmia Research Foundation
🇺🇸Austin, Texas, United States
Baylor Research Institute
🇺🇸Dallas, Texas, United States
Heart Rhythm Associates
🇺🇸The Woodlands, Texas, United States
CHRISTUS Northeast Texas Health System
🇺🇸Tyler, Texas, United States
The Rector and Visitors of the University of Virginia
🇺🇸Charlottesville, Virginia, United States
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
Vancouver Coastal Health Authority
🇨🇦Vancouver, British Columbia, Canada
St. Boniface Hospital Inc.
🇨🇦Winnipeg, Manitoba, Canada
Circulate Cardiac & Vascular Centre (CCVC)
🇨🇦Burlington, Ontario, Canada
Cambridge Cardiac Care Inc.
🇨🇦Cambridge, Ontario, Canada
Hamilton Health Sciences Corp
🇨🇦Hamilton, Ontario, Canada
Waterloo Wellington Cardiovascular Research Institute (WWCRI)
🇨🇦Kitchener, Ontario, Canada
Lawson Health Research Institute
🇨🇦London, Ontario, Canada
Southlake Regional Health Centre
🇨🇦Newmarket, Ontario, Canada
Partners in Advanced Cardiac Evaluation (PACE)
🇨🇦Newmarket, Ontario, Canada
Ottawa Heart Institute Research Corp
🇨🇦Ottawa, Ontario, Canada
Niagara Health Systems - St. Catharines
🇨🇦St Catharines, Ontario, Canada
Niagara Health System - Niagara Falls
🇨🇦St. Catharines, Ontario, Canada
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
Lawrence Park Cardiology
🇨🇦Toronto, Ontario, Canada
Institut de Cardiologie de Montreal (ICM)
🇨🇦Montréal, Quebec, Canada
Centre hospitalier de l'Université de Montréal
🇨🇦Montréal, Quebec, Canada
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
🇨🇦Québec, Quebec, Canada
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS)
🇨🇦Sherbrooke, Quebec, Canada
Prairie Valscular Research Inc. (PVRI)
🇨🇦Regina, Saskatchewan, Canada
Saskatchewan Health Authority
🇨🇦Saskatoon, Saskatchewan, Canada
Region Hospital Viborg
🇩🇰Viborg, Midtjylland, Denmark
Aarhus University Hospital (AUH)
🇩🇰Aarhus, Region Midt, Denmark
Infirmerie Protestante de Lyon
🇫🇷Caluire-et Cuire, Rhone Alpes, France
CVC Rhein-Main GmbH
🇩🇪Frankfurt, Hessen, Germany
MVZ CCB Frankfurt und Main-Taunus GbR
🇩🇪Frankfurt, Hessen, Germany
Westpfalz-Klinikum GmbH
🇩🇪Kaiserslautern, Rheinland-Pfalz, Germany
Katholisches Krankenhaus "St. Johann Nepomuk"
🇩🇪Erfurt, Thuringen, Germany