A Pilot Study of Edoxaban in Patients With Non-Valvular Atrial Fibrillation and Left Atrial Appendage Closure

Study Overview
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Brief Summary
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This is a single arm, open label, single site study assessing the feasibility of post-procedural edoxaban therapy in atrial fibrillation (AF) patients after clinically indicated WATCHMAN left atrial appendage (LAA) closure.

Detailed Description
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This is a single site, PI initiated pilot study. This study will enroll up to 75 patients who are clinically indicated for a Left Atrial Appendage (LAA) closure with the commercially available WATCHMAN device. Subjects will be enrolled if they meet study inclusion/exclusion criteria and have a successful LAA closure. All patients enrolled in the study will receive 6 weeks of edoxaban therapy. At 6 weeks post LAA closure a Transesophageal Echocardiography (TEE) will be performed. If the result is acceptable, edoxaban will be discontinued and the patient will be treated with dual antiplatelet therapy (aspirin and clopidogrel) until 6 month follow-up. After study completion, patients may be treated with aspirin monotherapy according to the FDA instructions for use for the WATCHMAN device, or according to operator discretion.

Official Title
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A Pilot Study of Edoxaban in Patients With Non-Valvular Atrial Fibrillation and Left Atrial Appendage Closure

Conditions
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Non-Valvular Atrial Fibrillation, Left Atrial Appendage Closure

Intervention / Treatment
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* Drug: Edoxaban
* Device: WATCHMAN LAA Closure
* Drug: Aspirin and Clopidogrel
* Drug: Aspirin and Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has documented paroxysmal, persistent, or permanent non-valvular AF (i.e., the patient has not been diagnosed with rheumatic mitral valve disease). LAA closure with the WATCHMAN device is planned The patient fulfills the FDA indication for WATCHMAN LAA closure The patient or legal representative is able to understand and willing to provide written informed consent to participate in the trial The patient is able and willing to return for required follow-up visits and examinations. The patient is 18 years of age or older Exclusion Criteria: Conditions other than atrial fibrillation that require anti-coagulation (e.g., a prosthetic heart valve) Stroke within the previous 7 days Hypersensitivity to edoxaban Moderate or severe mitral stenosis A need for aspirin at a dose of >81 mg a day A need for on-going treatment with dual antiplatelet therapy with aspirin and clopidogrel A need for on-going treatment with ticagrelor or prasugrel No LAA closure device implanted during procedure Procedural complication of LAA closure (e.g., stroke, systemic embolism, bleeding, vascular complication [e.g., groin hematoma >10cm, AV fistula, or pseudoaneurysm), or serious pericardial effusion) Planned surgery or invasive procedure within 6±2 weeks of enrollment

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Edoxaban Arm<br>All patients enrolled in the study will receive 6 weeks of edoxaban therapy, at which time a TEE will be performed. If the result is acceptable, edoxaban will be discontinued, and the patient will be treated with dual antiplatelet therapy (aspirin and clopidogrel) until 6 month follow-up. If device thrombus is present at 6 week TEE, patient will be transitioned to aspirin and adjusted-dose warfarin and LAA reassessed by TEE in 6 weeks; further warfarin will be continued according to operator preference. Subjects will have a 6 month follow-up visit prior to study completion. After study completion, patients may be treated with aspirin monotherapy according to the FDA instructions for use for the WATCHMAN device, or according to operator discretion. | Drug: Edoxaban<br>* Edoxaban 60mg once daily in patients with CrCl >50- ≤95 mL/min, or 30mg once daily in patients with CrCL 15-50 mL/min. If at 6 week TEE LAA closure is deemed acceptable by the operator (i.e., peri-device flow <5mm), edoxaban will be discontinued. Aspirin 81mg daily and clopidogrel 75mg daily will be administered until 6-month follow-up, then clopidogrel will be discontinued. If LAA unacceptable on 6-week TEE due to peri-device flow ≥5mm, edoxaban will be continued for an additional 6 weeks, and LAA reassessed by TEE If device thrombus is present at 6-week TEE, patient will be transitioned to aspirin 81 mg daily and adjusted-dose warfarin (goal INR, 2.0-3.0), and LAA reassessed by TEE in 6 weeks; further warfarin will be continued according to operator preference.<br>* Other names: Savaysa;Device: WATCHMAN LAA Closure<br>* Per Inclusion Criteria, enrolled subjects must have a successful Left Atrial Appendage (LAA) Closure using the WATCHMAN Device<br>Drug: Aspirin and Clopidogrel<br>* If at 6 week TEE LAA closure is deemed acceptable by the operator edoxaban will be discontinued, and aspirin 81mg daily and clopidogrel 75mg daily will be administered until 6-month follow-up. Then clopidogrel will be discontinued. Aspirin 325mg daily rather than 81mg daily can be administered according to operator preference after the 6-week follow-up visit.<br>Drug: Aspirin and Warfarin<br>* If device thrombus is present at 6-week TEE, patient will be transitioned to aspirin 81 mg daily and adjusted-dose warfarin (goal INR, 2.0-3.0), and LAA reassessed by TEE in 6 weeks; further warfarin will be continued according to operator preference.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death, stroke, systemic embolism or GUSTO outcomes | Composite of death, stroke, systemic embolism, or GUSTO moderate/severe bleeding will be collected at 6 weeks post-WATCHMAN LAA closure | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death, stroke, or systematic embolism outcomes | Composite of death, stroke, or systemic embolism at 6 weeks and 6 months | 6 weeks and 6 months | 
| Death, stroke, or systematic embolism or GUSTO outcomes | Composite of death, stroke, systemic embolism or GUSTO moderate/severe bleeding at 6 months | 6 months | 
| Device thrombus oucomes | TEE-confirmed device thrombus (according to core laboratory) at 6 weeks | 6 weeks | 
| TEE peri-device flow outcomes | Rate of peri-device flow >=5mm at 6 week follow-up TEE | 6 weeks | 
| GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding outcomes | Individual endpoints of GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding at 6 weeks and 6 months | 6 weeks and 6 months | 
| Premature discontinuation rate of study drug | Premature discontinuation rate of study drug before 6-week visit | 6 weeks | 
| Bleeding outcomes | Bleeding according to the months Bleeding Academic Research Consortium (BARC) criteria at 6 weeks and 6 months | 6 weeks and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Edoxaban, WATCHMAN device