Atrial Fibrillation, Stroke, Ischemic, Systemic Embolism
Conditions
Keywords
WATCHMAN, Left Atrial Appendage (LAA), LAA Device, Left Atrial Appendage Occlusion
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.
Interventions
DEVICEWATCHMAN device
Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
Sponsors
Hamilton Health Sciences Corporation
McMaster University
Population Health Research Institute
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Events Adjudication Committee is blinded to intervention assignment.
Intervention model description
Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
CONTACTProgram Director
PRINCIPAL_INVESTIGATORJeff Healey
Hamilton Health Sciences Corporation
Outcome results
None listed