Clinical trial NCT05963698: The Fourth Left Atrial Appendage Occlusion Study
Official title: The Fourth Left Atrial Appendage Occlusion Study (LAAOS-4)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Stroke, Ischemic
Systemic Embolism
Keywords: WATCHMAN
Left Atrial Appendage (LAA)
LAA Device
Left Atrial Appendage Occlusion
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: McMaster University
name: Population Health Research Institute
name: Boston Scientific Corporation
First posted: 2023-07-27
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. (a) Persistent or permanent atrial fibrillation OR (b) Paroxysmal atrial fibrillation in participants with a history of ischemic stroke or systemic embolism
2. Increased risk of stroke, defined as a CHA2DS2-VASc stroke risk score of ≥ 4. \[Note: the acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female).\]
3. 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.

Exclusion Criteria:

1. Age \< 18 years
2. Current left atrial appendage thrombus
3. Prior left atrial appendage occlusion or removal (surgical or percutaneous)
4. Prior percutaneous atrial septal defect or patent foramen ovale closure
5. Prior atrial fibrillation ablation unless evidence of recurrent qualifying atrial fibrillation present at least 30 days following ablation
6. Planned atrial fibrillation ablation within 90 days of enrollment
7. Individuals being treated with direct thrombin inhibitors
8. Women of childbearing potential unless they agree to employ effective birth control methods throughout the study
9. Anticipated life-expectancy of \< 2 years
10. Patient unable or willing to give informed consent

Primary outcomes:
measure: Ischemic stroke or systemic embolism
timeFrame: 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).
Secondary outcomes:
measure: All-cause stroke or systemic embolism
timeFrame: 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).
measure: All-cause stroke, systemic embolism, or transient ischemic attack (TIA)
timeFrame: 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).
measure: Montreal Cognitive Assessment (MoCA) Score
timeFrame: 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).
measure: New disabling ischemic strokes
timeFrame: 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).
measure: Cardiovascular mortality
timeFrame: 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).
measure: All-cause mortality
timeFrame: 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).
Other outcomes:
measure: Non-procedural Major Bleeding
timeFrame: 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).
measure: Hospitalization for any cause
timeFrame: 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).
measure: Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy
timeFrame: 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).
measure: Myocardial Infarction
timeFrame: 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).
measure: Device and procedural-related outcomes: Device-related thrombus
timeFrame: 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).
measure: Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure
timeFrame: 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).
measure: Device and procedural-related outcomes: Peri-procedural major bleeding
timeFrame: 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).
Locations:
city: Birmingham
country: United States
facility: Affinity Hospital dba Grandview Medical Center
state: Alabama
city: Jonesboro
country: United States
facility: Arrhythmia Research Group
state: Arkansas
city: Fountain Valley
country: United States
facility: Memorial Health Services
state: California
city: Sacramento
country: United States
facility: Sutter Valley Hospitals dba Sutter Institute for Medical Research
state: California
city: Jacksonville
country: United States
facility: St. Vincent's Health System
state: Florida
city: Coeur d'Alene
country: United States
facility: Kootenai Health Inc.
state: Idaho
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network Inc.
state: Indiana
city: West Des Moines
country: United States
facility: MercyOne Iowa Heart Center
state: Iowa
city: Lexington
country: United States
facility: Babtist Health Lexington
state: Kentucky
city: Burlington
country: United States
facility: Lahey Clinic Inc.
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Manhasset
country: United States
facility: The Feinstein Institutes for Medical Research
state: New York
city: New York
country: United States
facility: NYU Grossman School of Medicine
state: New York
city: New York
country: United States
facility: Cornell University for and on behalf of its Joan & Sanford I. Weill Medical College and The New York Presbyterian Hospital
state: New York
city: Asheville
country: United States
facility: Mission Hospital HCA
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Inc.
state: Ohio
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: The Woodlands
country: United States
facility: Heart Rhythm Associates
state: Texas
city: Tyler
country: United States
facility: CHRISTUS Northeast Texas Health System
state: Texas
city: Charlottesville
country: United States
facility: The Rector and Visitors of the University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Authority
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface Hospital Inc.
state: Manitoba
city: Burlington
country: Canada
facility: Circulate Cardiac & Vascular Centre (CCVC)
state: Ontario
city: Cambridge
country: Canada
facility: Cambridge Cardiac Care Inc.
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corp
state: Ontario
city: Kitchener
country: Canada
facility: Waterloo Wellington Cardiovascular Research Institute (WWCRI)
state: Ontario
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Newmarket
country: Canada
facility: Partners in Advanced Cardiac Evaluation (PACE)
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute Research Corp
state: Ontario
city: St Catharines
country: Canada
facility: Niagara Health Systems - St. Catharines
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System - Niagara Falls
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Lawrence Park Cardiology
state: Ontario
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montreal (ICM)
state: Quebec
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS)
state: Quebec
city: Regina
country: Canada
facility: Prairie Valscular Research Inc. (PVRI)
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatchewan Health Authority
state: Saskatchewan
city: Viborg
country: Denmark
facility: Region Hospital Viborg
state: Midtjylland
city: Aarhus
country: Denmark
facility: Aarhus University Hospital (AUH)
state: Region Midt
city: Caluire-et Cuire
country: France
facility: Infirmerie Protestante de Lyon
state: Rhone Alpes
city: Frankfurt
country: Germany
facility: CVC Rhein-Main GmbH
state: Hessen
city: Frankfurt
country: Germany
facility: MVZ CCB Frankfurt und Main-Taunus GbR
state: Hessen
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
state: Rheinland-Pfalz
city: Erfurt
country: Germany
facility: Katholisches Krankenhaus "St. Johann Nepomuk"
state: Thuringen
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Jeff Healey
role: PRINCIPAL_INVESTIGATOR
References: