Assessment of the WATCHMAN™ Device in Patients Unsuitable for Oral Anticoagulation

Study Overview
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Brief Summary
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The purpose of this study is to establish the safety and effectiveness of the WATCHMAN™ Left Atrial Appendage Closure (LAAC) Device, including the post-implant medication regimen, for subjects with non-valvular atrial fibrillation who are deemed not to be eligible for anti-coagulation therapy to reduce the risk of stroke.

Detailed Description
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The ASAP-TOO study is a prospective, randomized, multi-center, global investigation to establish the safety and effectiveness of the WATCHMAN Device for subjects with non-valvular atrial fibrillation who are deemed not suitable for anti-coagulation therapy to reduce the risk of stroke. Subjects will be randomized in a ratio of 2 Device to 1 Control to receive the WATCHMAN LAA closure device (Device) or the control treatment of single antiplatelet medication or no medication at the discretion of the study physician (Control). All randomized subjects will follow the protocol required tests and assessments at each scheduled follow-up visit.

Official Title
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Assessment of the WATCHMAN™ Device in Patients Unsuitable for Oral Anticoagulation (ASAP-TOO)

Conditions
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Stroke

Intervention / Treatment
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* Device: WATCHMAN LAAC Device Implant
* Drug: Single Antiplatelet Therapy or No Therapy (Control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is of legal age to participate in the study per the laws of their respective geography. The subject has documented paroxysmal, persistent, permanent or long-term/longstanding persistent non-valvular atrial fibrillation (i.e., the subject has not been diagnosed with rheumatic mitral valvular heart disease). The subject has a calculated CHA2DS2-VASc score of 2 or greater. The subject is deemed by two study physicians to be unsuitable for oral anticoagulation. The subject is deemed by a study physician to be suitable for the defined protocol pharmacologic regimen of aspirin and clopidogrel therapy following WATCHMAN Closure Device implant. The subject or legal representative is able to understand and willing to provide written informed consent to participate in the trial. The subject is able and willing to return for required follow-up visits and examinations. Exclusion Criteria: The subject is unable or unwilling to return for required follow-up visits and examinations. The subject had or is planning to have any invasive cardiac procedure within 30 days prior to randomization (e.g., cardioversion, ablation). The subject is planning to have any cardiac or non-cardiac invasive or surgical procedure that would necessitate stopping or modifying the protocol required medication regimen within 90 days after the WATCHMAN Closure Device implant (e.g., cardioversion, ablation, cataract surgery). The subject had a prior stroke (of any cause) or TIA within the 30 days prior to randomization. The subject had a prior BARC type 3 or 4 bleeding event within the 14 days prior to randomization. Lack of resolution of related clinical sequelae, or planned and pending interventions to resolve bleeding/bleeding source, are a further exclusion regardless of timing of the bleeding event. The subject has a history of atrial septal repair or has an ASD/PFO device. The subject has an implanted mechanical valve prosthesis in any position. The subject suffers from New York Heart Association Class IV Congestive Heart Failure. The subject has LVEF < 30%. The subject is of childbearing potential and is, or plans to become pregnant during the time of the study (method of assessment upon study physician's discretion). The subject is currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments. Each instance should be brought to the attention of the sponsor to determine eligibility. The subject has a life expectancy of less than two years. The subject has a known or suspected hypercoagulable state.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WATCHMAN (Device)<br>WATCHMAN LAAC Device implant including modified post-implant drug regimen. | Device: WATCHMAN LAAC Device Implant<br>* WATCHMAN LAAC Implant<br>|
| Active Comparator: Control<br>Single antiplatelet therapy or no therapy (Control) at the discretion of the study physician for the duration of the trial. | Drug: Single Antiplatelet Therapy or No Therapy (Control)<br>* Single Antiplatelet Therapy or No Therapy at the discretion of the study physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary 7-Day Device/Procedural Safety Endpoint | The primary safety endpoint is the 7-day combined rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention. | 7 days | 
| Primary Efficacy Endpoint - time to first event of ischemic stroke or systemic embolism. | The primary efficacy endpoint is the comparison of time to first event of ischemic stroke and systemic embolism. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint - Composite of All Stroke and Cardiovascular or Unknown Death | The occurrence of stroke (including ischemic and/or hemorrhagic), cardiovascular death (cardiovascular and/or unexplained cause) and systemic embolism | 5 years | 
| Secondary Endpoint - Major Bleeding | The occurrence of major bleeding (defined as a BARC Type 3 or 5 event) | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-valvular atrial fibrillation, Left atrial appendage