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

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ClinicalTrials.gov Identifier: NCT03088072
Recruitment Status : Recruiting
First Posted : March 23, 2017
Last Update Posted : July 11, 2017
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Matthew J Price, Scripps Health

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
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 : March 23, 2017
Estimated Primary Completion Date : November 30, 2018
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Edoxaban

Arm Intervention/treatment
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 Name: 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.




Primary Outcome Measures :
  1. Death, stroke, systemic embolism or GUSTO outcomes [ Time Frame: 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 :
  1. Death, stroke, or systematic embolism outcomes [ Time Frame: 6 weeks and 6 months ]
    Composite of death, stroke, or systemic embolism at 6 weeks and 6 months

  2. Death, stroke, or systematic embolism or GUSTO outcomes [ Time Frame: 6 months ]
    Composite of death, stroke, systemic embolism or GUSTO moderate/severe bleeding at 6 months

  3. Device thrombus oucomes [ Time Frame: 6 weeks ]
    TEE-confirmed device thrombus (according to core laboratory) at 6 weeks

  4. TEE peri-device flow outcomes [ Time Frame: 6 weeks ]
    Rate of peri-device flow >=5mm at 6 week follow-up TEE

  5. GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding outcomes [ Time Frame: 6 weeks and 6 months ]
    Individual endpoints of GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding at 6 weeks and 6 months

  6. Premature discontinuation rate of study drug [ Time Frame: 6 weeks ]
    Premature discontinuation rate of study drug before 6-week visit

  7. Bleeding outcomes [ Time Frame: 6 weeks and 6 months ]
    Bleeding according to the months Bleeding Academic Research Consortium (BARC) criteria at 6 weeks and 6 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03088072


Contacts
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Contact: Catchpole Heather 858 824 4248 Catchpole.Heather@scrippshealth.org

Locations
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United States, California
Scripps Health Recruiting
La Jolla, California, United States, 92037
Contact: Heather Catchpole    858-824-4248    Catchpole.Heather@scrippshealth.org   
Sponsors and Collaborators
Scripps Health
Daiichi Sankyo, Inc.
Investigators
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Principal Investigator: Matthew J Price, MD Scripps Health

Publications:

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Responsible Party: Matthew J Price, Principal Investigator, Scripps Health
ClinicalTrials.gov Identifier: NCT03088072     History of Changes
Other Study ID Numbers: IRB-17-6931
First Posted: March 23, 2017    Key Record Dates
Last Update Posted: July 11, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Matthew J Price, Scripps Health:
Edoxaban
WATCHMAN device

Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Aspirin
Clopidogrel
Edoxaban
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Anticoagulants