The Fourth Left Atrial Appendage Occlusion Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Fourth Left Atrial Appendage Occlusion Study (LAAOS-4)

Conditions
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Atrial Fibrillation, Stroke, Ischemic, Systemic Embolism

Intervention / Treatment
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* Device: WATCHMAN device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WATCHMAN device<br>Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device | Device: WATCHMAN device<br>* Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device<br>|
| No Intervention: Standard Care<br>Participants will receive local, standard medical care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ischemic stroke or systemic embolism | 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 | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause stroke or systemic embolism | 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 | 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). | 
| All-cause stroke, systemic embolism, or transient ischemic attack (TIA) | Time from randomization to first occurrence of 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). | 
| Montreal Cognitive Assessment (MoCA) Score | Proportion of participants with a decrease of two or more points on the MoCA score at either year 2 or end of study | 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). | 
| New disabling ischemic strokes | Time from randomization to first occurrence of disabling ischemic strokes with modified Rankin Score (mRS) >2, measured at 90 days post-stroke | 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). | 
| Cardiovascular mortality | Time from randomization to 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). | 
| All-cause mortality | Time from randomization to 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WATCHMAN, Left Atrial Appendage (LAA), LAA Device, Left Atrial Appendage Occlusion