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

Sponsor

Scripps Health (Other)

Overall Status

Unknown status

CT.gov ID

NCT03088072

Collaborator

Daiichi Sankyo, Inc. (Industry)

Enrollment

Location

Arm

33.3

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Valvular Atrial Fibrillation Left Atrial Appendage Closure	Drug: Edoxaban Device: WATCHMAN LAA Closure Drug: Aspirin and Clopidogrel Drug: Aspirin and Warfarin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 23, 2017

Anticipated Primary Completion Date :

Nov 30, 2018

Anticipated Study Completion Date :

Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Edoxaban Arm 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 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. Other Names: Savaysa Device: WATCHMAN LAA Closure Per Inclusion Criteria, enrolled subjects must have a successful Left Atrial Appendage (LAA) Closure using the WATCHMAN Device Drug: Aspirin and Clopidogrel 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. Drug: Aspirin and Warfarin 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.

Arm

Intervention/Treatment

Other: Edoxaban Arm

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

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.

Other Names:

Savaysa

Device: WATCHMAN LAA Closure

Per Inclusion Criteria, enrolled subjects must have a successful Left Atrial Appendage (LAA) Closure using the WATCHMAN Device

Drug: Aspirin and Clopidogrel

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.

Drug: Aspirin and Warfarin

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.

Outcome Measures

Primary Outcome Measures

Death, stroke, systemic embolism or GUSTO outcomes [6 weeks]
Composite of death, stroke, systemic embolism, or GUSTO moderate/severe bleeding will be collected at 6 weeks post-WATCHMAN LAA closure

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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