The Fourth Left Atrial Appendage Occlusion Study

Not Applicable

Recruiting

• Conditions: Atrial Fibrillation; Stroke, Ischemic; Systemic Embolism

• 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.

Study Timeline

• Study First Submitted: 2023-07-05
• Study First Submitted QC: 2023-07-18
• Study First Posted: 2023-07-27
• Study Start: 2023-11-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-21
• Primary Completion: 2029-09-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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 embolism
New 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)

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

St. Vincent's Health System; 🇺🇸 Jacksonville, Florida, United States

Kootenai Health Inc.; 🇺🇸 Coeur d'Alene, Idaho, 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

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