LAAOS-4: The Fourth Left Atrial Appendage Occlusion Study

• Sponsor: Hamilton Health Sciences Corporation (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05963698
• Collaborator: McMaster University (Other), Population Health Research Institute (Other), Boston Scientific Corporation (Industry)
• Enrollment: 4,000
• Arms: 2
• Anticipated Duration (Months): 75

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Stroke, Ischemic; Systemic Embolism	Device: WATCHMAN device	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 4000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Controlled TrialRandomized Controlled Trial
• Masking: Single (Outcomes Assessor)
• Masking Description: Events Adjudication Committee is blinded to intervention assignment.
• Primary Purpose: Treatment
• Official Title: The Fourth Left Atrial Appendage Occlusion Study (LAAOS-4)
• Anticipated Study Start Date: Sep 1, 2023
• Anticipated Primary Completion Date: Sep 1, 2029
• Anticipated Study Completion Date: Dec 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WATCHMAN device Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device	Device: WATCHMAN device; Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
No Intervention: Standard Care Participants will receive local, standard medical care

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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)

3. 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

4. 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

5. 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

6. 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

Other Outcome Measures

1. Non-procedural Major Bleeding [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 non-procedural Major Bleeding (International Society on Thrombosis and Haemostasis (ISTH) definition; excluding WATCHMAN-related bleeding within 14 days of implant)

2. Hospitalization for any cause [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 hospitalization for any cause

3. Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy [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 heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy

4. Myocardial Infarction [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 Myocardial Infarction (4th Universal definition)

5. Device and procedural-related outcomes: Device-related thrombus [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 device-related thrombus (thrombus formed on the surface of the WATCHMAN device)

6. Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure [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 incomplete LAA closure

7. Device and procedural-related outcomes: Peri-procedural major bleeding [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 peri-procedural major bleeding (ISTH definition; within 14 days following the procedure)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Hamilton Health Sciences Corporation
• McMaster University
• Population Health Research Institute
• Boston Scientific Corporation

Investigators

• Principal Investigator: Jeff Healey, Hamilton Health Sciences Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hamilton Health Sciences Corporation
• ClinicalTrials.gov Identifier: NCT05963698
• Other Study ID Numbers: LAAOS-4
• First Posted: Jul 27, 2023
• Last Update Posted: Jul 27, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Hamilton Health Sciences Corporation: WATCHMAN; Left Atrial Appendage (LAA); LAA Device; Left Atrial Appendage Occlusion
• Additional relevant MeSH terms: Ischemic Stroke; Atrial Fibrillation; Embolism

Study Results

No Results Posted as of Jul 27, 2023