The Fourth Left Atrial Appendage Occlusion Study

Atrial Fibrillation Clinical Trial

— LAAOS-4  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05963698
• Other study ID #: LAAOS-4
• Status: Recruiting
• Phase: N/A
• Start date: November 30, 2023
• Est. completion date: December 1, 2029

Study information

• Verified date: December 2023
• Source: Hamilton Health Sciences Corporation
• Contact: Program Director
• Phone: 905-521-2100
• Email: LAAOS-4[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: December 1, 2029
• Est. primary completion date: September 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Embolism
• Ischemic Stroke
• Stroke, Ischemic
• Systemic Embolism

Intervention

Device:
• WATCHMAN device
Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences Corp	Hamilton	Ontario
United States	Arrhythmia Research Group	Jonesboro	Arkansas

Sponsors (4)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	Boston Scientific Corporation, McMaster University, Population Health Research Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Non-procedural Major Bleeding	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)	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	Hospitalization for any cause	Time from randomization to first occurrence of 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).
Other	Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy	Time from randomization to first occurrence of 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).
Other	Myocardial Infarction	Time from randomization to first occurrence of Myocardial Infarction (4th Universal definition)	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	Device and procedural-related outcomes: Device-related thrombus	Proportion of participants with device-related thrombus (thrombus formed on the surface of the WATCHMAN device)	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	Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure	Proportion of participants with incomplete 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).
Other	Device and procedural-related outcomes: Peri-procedural major bleeding	Proportion of participants with peri-procedural major bleeding (ISTH definition; within 14 days following the procedure)	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).
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).