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

Non-Valvular Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03088072
• Other study ID #: IRB-17-6931
• Status: Recruiting
• Phase: Phase 4
• First received: March 9, 2017
• Last updated: July 7, 2017
• Start date: March 23, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: July 2017
• Source: Scripps Health
• Contact: Catchpole Heather
• Phone: 858 824 4248
• Email: Catchpole.Heather[@]scrippshealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 31, 2019
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Left Atrial Appendage Closure
• Non-Valvular Atrial Fibrillation

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
United States	Scripps Health	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
Scripps Health	Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

Bösche LI, Afshari F, Schöne D, Ewers A, Mügge 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. — View 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. — View 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. — View Citation

Lamberts M, Gislason GH, Lip GY, Lassen JF, Olesen JB, Mikkelsen AP, Sørensen R, Køber 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. — View 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. — View 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. — View 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. Review. — View Citation

Price MJ, Reddy VY, Valderrábano 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):1925-32. doi: 10.1016/j.jcin.2015.08.035. Epub 2015 Nov 25. — View Citation

Price MJ, Valderrábano 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. Review. — View Citation

Price MJ. Left atrial appendage occlusion with the WATCHMAN™ for stroke prevention in atrial fibrillation. Rev Cardiovasc Med. 2014;15(2):142-51. Review. — View Citation

Reddy VY, Möbius-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. — View 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). pii: e002587. doi: 10.1161/JAHA.115.002587. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

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