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

Primary Purpose

Non-Valvular Atrial Fibrillation, Left Atrial Appendage Closure

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Edoxaban
WATCHMAN LAA Closure
Aspirin and Clopidogrel
Aspirin and Warfarin
Sponsored by
Scripps Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Valvular Atrial Fibrillation focused on measuring Edoxaban, WATCHMAN device

Eligibility Criteria

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

Sites / Locations

  • Scripps HealthRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Edoxaban Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
March 9, 2017
Last Updated
July 7, 2017
Sponsor
Scripps Health
Collaborators
Daiichi Sankyo, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03088072
Brief Title
A Pilot Study of Edoxaban in Patients With Non-Valvular Atrial Fibrillation and Left Atrial Appendage Closure
Official Title
A Pilot Study of Edoxaban in Patients With Non-Valvular Atrial Fibrillation and Left Atrial Appendage Closure
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Unknown status
Study Start Date
March 23, 2017 (Actual)
Primary Completion Date
November 30, 2018 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Scripps Health
Collaborators
Daiichi Sankyo, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Valvular Atrial Fibrillation, Left Atrial Appendage Closure
Keywords
Edoxaban, WATCHMAN device

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Edoxaban Arm
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Edoxaban
Other Intervention Name(s)
Savaysa
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
WATCHMAN LAA Closure
Intervention Description
Per Inclusion Criteria, enrolled subjects must have a successful Left Atrial Appendage (LAA) Closure using the WATCHMAN Device
Intervention Type
Drug
Intervention Name(s)
Aspirin and Clopidogrel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Aspirin and Warfarin
Intervention Description
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 Measure Information:
Title
Death, stroke, systemic embolism or GUSTO outcomes
Description
Composite of death, stroke, systemic embolism, or GUSTO moderate/severe bleeding will be collected at 6 weeks post-WATCHMAN LAA closure
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Death, stroke, or systematic embolism outcomes
Description
Composite of death, stroke, or systemic embolism at 6 weeks and 6 months
Time Frame
6 weeks and 6 months
Title
Death, stroke, or systematic embolism or GUSTO outcomes
Description
Composite of death, stroke, systemic embolism or GUSTO moderate/severe bleeding at 6 months
Time Frame
6 months
Title
Device thrombus oucomes
Description
TEE-confirmed device thrombus (according to core laboratory) at 6 weeks
Time Frame
6 weeks
Title
TEE peri-device flow outcomes
Description
Rate of peri-device flow >=5mm at 6 week follow-up TEE
Time Frame
6 weeks
Title
GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding outcomes
Description
Individual endpoints of GUSTO mild, moderate, severe, and GUSTO moderate/severe bleeding at 6 weeks and 6 months
Time Frame
6 weeks and 6 months
Title
Premature discontinuation rate of study drug
Description
Premature discontinuation rate of study drug before 6-week visit
Time Frame
6 weeks
Title
Bleeding outcomes
Description
Bleeding according to the months Bleeding Academic Research Consortium (BARC) criteria at 6 weeks and 6 months
Time Frame
6 weeks and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catchpole Heather
Phone
858 824 4248
Email
Catchpole.Heather@scrippshealth.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew J Price, MD
Organizational Affiliation
Scripps Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Scripps Health
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Catchpole
Phone
858-824-4248
Email
Catchpole.Heather@scrippshealth.org

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
25001625
Citation
Price MJ, Valderrabano M. Left atrial appendage closure to prevent stroke in patients with atrial fibrillation. Circulation. 2014 Jul 8;130(2):202-12. doi: 10.1161/CIRCULATIONAHA.114.009060. No abstract available.
Results Reference
background
PubMed Identifier
25066488
Citation
Price MJ, Holmes DR. Mechanical closure devices for atrial fibrillation. Trends Cardiovasc Med. 2014 Aug;24(6):225-31. doi: 10.1016/j.tcm.2014.06.001. Epub 2014 Jun 8.
Results Reference
background
PubMed Identifier
26908401
Citation
Xu H, Ruff CT, Giugliano RP, Murphy SA, Nordio F, Patel I, Shi M, Mercuri M, Antman EM, Braunwald E. Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF-TIMI48 Trial. J Am Heart Assoc. 2016 Feb 23;5(2):e002587. doi: 10.1161/JAHA.115.002587.
Results Reference
background
PubMed Identifier
23271794
Citation
Dans AL, Connolly SJ, Wallentin L, Yang S, Nakamya J, Brueckmann M, Ezekowitz M, Oldgren J, Eikelboom JW, Reilly PA, Yusuf S. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013 Feb 5;127(5):634-40. doi: 10.1161/CIRCULATIONAHA.112.115386. Epub 2012 Dec 27.
Results Reference
background
PubMed Identifier
24470482
Citation
Lamberts M, Gislason GH, Lip GY, Lassen JF, Olesen JB, Mikkelsen AP, Sorensen R, Kober L, Torp-Pedersen C, Hansen ML. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation. 2014 Apr 15;129(15):1577-85. doi: 10.1161/CIRCULATIONAHA.113.004834. Epub 2014 Jan 27.
Results Reference
background
PubMed Identifier
26627989
Citation
Price MJ, Reddy VY, Valderrabano M, Halperin JL, Gibson DN, Gordon N, Huber KC, Holmes DR Jr. Bleeding Outcomes After Left Atrial Appendage Closure Compared With Long-Term Warfarin: A Pooled, Patient-Level Analysis of the WATCHMAN Randomized Trial Experience. JACC Cardiovasc Interv. 2015 Dec 28;8(15):1925-1932. doi: 10.1016/j.jcin.2015.08.035. Epub 2015 Nov 25.
Results Reference
background
PubMed Identifier
23036896
Citation
Lopes RD, Al-Khatib SM, Wallentin L, Yang H, Ansell J, Bahit MC, De Caterina R, Dorian P, Easton JD, Erol C, Ezekowitz JA, Gersh BJ, Granger CB, Hohnloser SH, Horowitz J, Hylek EM, McMurray JJ, Mohan P, Vinereanu D, Alexander JH. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012 Nov 17;380(9855):1749-58. doi: 10.1016/S0140-6736(12)60986-6. Epub 2012 Oct 2. Erratum In: Lancet. 2013 Jan 19;381(9862):204.
Results Reference
background
PubMed Identifier
26467851
Citation
Bosche LI, Afshari F, Schone D, Ewers A, Mugge A, Gotzmann M. Initial Experience With Novel Oral Anticoagulants During the First 45 Days After Left Atrial Appendage Closure With the Watchman Device. Clin Cardiol. 2015 Dec;38(12):720-4. doi: 10.1002/clc.22478. Epub 2015 Oct 14.
Results Reference
background
PubMed Identifier
23583249
Citation
Reddy VY, Mobius-Winkler S, Miller MA, Neuzil P, Schuler G, Wiebe J, Sick P, Sievert H. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol. 2013 Jun 25;61(25):2551-6. doi: 10.1016/j.jacc.2013.03.035. Epub 2013 Apr 10.
Results Reference
background
PubMed Identifier
16765759
Citation
ACTIVE Writing Group of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, Pfeffer M, Hohnloser S, Yusuf S. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903-12. doi: 10.1016/S0140-6736(06)68845-4.
Results Reference
background
PubMed Identifier
21309657
Citation
Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364(9):806-17. doi: 10.1056/NEJMoa1007432. Epub 2011 Feb 10.
Results Reference
background
PubMed Identifier
21670242
Citation
Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
Results Reference
background
PubMed Identifier
25051131
Citation
Price MJ. Left atrial appendage occlusion with the WATCHMAN for stroke prevention in atrial fibrillation. Rev Cardiovasc Med. 2014;15(2):142-51. doi: 10.3909/ricm0733.
Results Reference
background

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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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