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

Primary Purpose

Atrial Fibrillation, Stroke, Ischemic, Systemic Embolism

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
WATCHMAN device
Sponsored by
Hamilton Health Sciences Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring WATCHMAN, Left Atrial Appendage (LAA), LAA Device, Left Atrial Appendage Occlusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    WATCHMAN device

    Standard Care

    Arm Description

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

    Participants will receive local, standard medical care

    Outcomes

    Primary Outcome Measures

    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

    Secondary Outcome Measures

    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
    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)
    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
    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
    Cardiovascular mortality
    Time from randomization to cardiovascular mortality
    All-cause mortality
    Time from randomization to all-cause mortality

    Full Information

    First Posted
    July 5, 2023
    Last Updated
    September 20, 2023
    Sponsor
    Hamilton Health Sciences Corporation
    Collaborators
    McMaster University, Population Health Research Institute, Boston Scientific Corporation
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05963698
    Brief Title
    The Fourth Left Atrial Appendage Occlusion Study
    Acronym
    LAAOS-4
    Official Title
    The Fourth Left Atrial Appendage Occlusion Study (LAAOS-4)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    September 1, 2029 (Anticipated)
    Study Completion Date
    December 1, 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hamilton Health Sciences Corporation
    Collaborators
    McMaster University, Population Health Research Institute, Boston Scientific Corporation

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    Yes
    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Atrial Fibrillation, Stroke, Ischemic, Systemic Embolism
    Keywords
    WATCHMAN, Left Atrial Appendage (LAA), LAA Device, Left Atrial Appendage Occlusion

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Randomized Controlled Trial
    Masking
    Outcomes Assessor
    Masking Description
    Events Adjudication Committee is blinded to intervention assignment.
    Allocation
    Randomized
    Enrollment
    4000 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    WATCHMAN device
    Arm Type
    Experimental
    Arm Description
    Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
    Arm Title
    Standard Care
    Arm Type
    No Intervention
    Arm Description
    Participants will receive local, standard medical care
    Intervention Type
    Device
    Intervention Name(s)
    WATCHMAN device
    Intervention Description
    Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
    Primary Outcome Measure Information:
    Title
    Ischemic stroke or systemic embolism
    Description
    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
    Time Frame
    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 Measure Information:
    Title
    All-cause stroke or systemic embolism
    Description
    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
    Time Frame
    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).
    Title
    All-cause stroke, systemic embolism, or transient ischemic attack (TIA)
    Description
    Time from randomization to first occurrence of all-cause stroke, systemic embolism or transient ischemic attack (TIA)
    Time Frame
    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).
    Title
    Montreal Cognitive Assessment (MoCA) Score
    Description
    Proportion of participants with a decrease of two or more points on the MoCA score at either year 2 or end of study
    Time Frame
    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).
    Title
    New disabling ischemic strokes
    Description
    Time from randomization to first occurrence of disabling ischemic strokes with modified Rankin Score (mRS) >2, measured at 90 days post-stroke
    Time Frame
    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).
    Title
    Cardiovascular mortality
    Description
    Time from randomization to cardiovascular mortality
    Time Frame
    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).
    Title
    All-cause mortality
    Description
    Time from randomization to all-cause mortality
    Time Frame
    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 Pre-specified Outcome Measures:
    Title
    Non-procedural Major Bleeding
    Description
    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)
    Time Frame
    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).
    Title
    Hospitalization for any cause
    Description
    Time from randomization to first occurrence of hospitalization for any cause
    Time Frame
    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).
    Title
    Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy
    Description
    Time from randomization to first occurrence of heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy
    Time Frame
    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).
    Title
    Myocardial Infarction
    Description
    Time from randomization to first occurrence of Myocardial Infarction (4th Universal definition)
    Time Frame
    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).
    Title
    Device and procedural-related outcomes: Device-related thrombus
    Description
    Proportion of participants with device-related thrombus (thrombus formed on the surface of the WATCHMAN device)
    Time Frame
    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).
    Title
    Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure
    Description
    Proportion of participants with incomplete LAA closure
    Time Frame
    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).
    Title
    Device and procedural-related outcomes: Peri-procedural major bleeding
    Description
    Proportion of participants with peri-procedural major bleeding (ISTH definition; within 14 days following the procedure)
    Time Frame
    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).

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Tara McCready
    Phone
    905-521-2100
    Email
    tara.mccready@phri.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jeff Healey
    Organizational Affiliation
    Hamilton Health Sciences Corporation
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    The Fourth Left Atrial Appendage Occlusion Study

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