Edoxaban Treatment Versus Vitamin K Antagonist (VKA) in Patients With Atrial Fibrillation (AF) Undergoing Catheter Ablation (ELIMINATE-AF)

Study Description

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Brief Summary:

There are insufficient data on the safety and efficacy of edoxaban therapy in subjects with AF following catheter ablation. This phase 3b study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a VKA-based antithrombotic regimen in subjects with AF following catheter ablation. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation	Drug: Edoxaban; Drug: VKA-Based Regimen	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	560 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Prospective, Randomized, Open-Label, Blinded Endpoint Evaluation (PROBE) Parallel Group Study Comparing Edoxaban vs. VKA in Subjects Undergoing Catheter Ablation of Non-valvular Atrial Fibrillation (ELIMINATE-AF)
Actual Study Start Date :	March 21, 2017
Estimated Primary Completion Date :	November 2018
Estimated Study Completion Date :	November 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Edoxaban-based regimen; Edoxaban-based regimen for 21 days pre- and 90 days post-ablation period.	Drug: Edoxaban; Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects.; Other Name: Lixiana
Active Comparator: VKA-based regimen; VKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)	Drug: VKA-Based Regimen; Dosed at International Normalised Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in Canada, Italy, Poland, Hungary, Czech Republic, UK, Taiwan and Korea.; Other Name: Warfarin Drug: VKA-Based Regimen; Dosed at INR levels. Standard of Care treatment in Germany, Belgium, and the Netherlands.; Other Names: Phenprogamma; Phenprocoumon Drug: VKA-Based Regimen; Dosed at INR levels. Standard of Care treatment in France.; Other Names: Previscan; Fluindione Drug: VKA-Based Regimen; Dosed at INR levels. Standard of Care treatment in Spain.; Other Names: Sintrom; Acenocoumarol

Outcome Measures

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Primary Outcome Measures :

1. Number of participants who experienced composite of all-cause death, stroke and major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH) [ Time Frame: Day 1 to Day 90 ]
   To compare descriptively the incidence of the composite of all-cause death, stroke (ischemic, hemorrhagic, or undetermined) and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) in the edoxaban group against the vitamin K antagonist (VKA) group in subjects undergoing catheter ablation of atrial fibrillation (AF)
2. Number of participants who experienced major bleeding according to the ISTH definition [ Time Frame: Day 1 to Day 90 ]

Secondary Outcome Measures :

1. Number of participants who experienced composite of all-cause death, stroke and major bleeding according to ISTH and alternate definitions [ Time Frame: Day 1 to Day 90 ]
2. Number of participants who experienced the composite of stroke, systemic embolic events (SEE), and cardiovascular (CV) mortality [ Time Frame: Day 1 to Day 90 ]
3. Number of participants who experienced the composite of stroke, SEE, and all-cause mortality [ Time Frame: Day 1 to Day 90 ]
4. Number of participants who experienced the composite of stroke, and transient ischemic attack (TIA) [ Time Frame: Day 1 to Day 90 ]
5. Number of participants who experienced stroke [ Time Frame: Day 1 to Day 90 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Male or female at least 18 years of age with documented history of paroxysmal (lasting ≤7 days), persistent (lasting >7 days but ≤12 months) or long-standing [long-lasting] persistent (>12 months) non-valvular AF. Duration of AF can be confirmed by any electrical tracing or a recording in the subject's medical records (e.g., medical chart, hospital discharge summary).
• Subject is eligible and is scheduled for either radio frequency (RF) or cryoballoon catheter ablation (both first and repeated procedure included).
• Signed informed consent form (ICF).

Exclusion Criteria:

• AF considered to be of a transient or reversible nature (such as in myocarditis, post-surgery, ionic disturbances, thyrotoxicosis, pneumonia, severe anemia etc.).
• Subject post stroke, or with a systemic thromboembolic event within the past 6 months prior to randomization.
• Subject has a thrombus in the left atrial appendage (LAA), left atrium (LA), left ventricle (LV), or aorta, or an intracardial mass.
• Subject had a myocardial infarction (MI) within the 2 months prior to randomization or coronary artery bypass graft (CABG) surgery within 3 months prior to the randomization.
• Subject has signs of bleeding, history of clinically-relevant bleeding according to ISTH, or conditions associated with high risk of bleeding
• Subjects with any contraindication for anticoagulant agents.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 81 Study Locations

Sponsors and Collaborators

Daiichi Sankyo Europe, GmbH

Investigators

Study Director:	Global Clinical Leader	Daiichi Sankyo, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016 Nov;18(11):1609-1678. Epub 2016 Aug 27.

Crawford T, Oral H. Current status and outcomes of catheter ablation for atrial fibrillation. Heart Rhythm. 2009 Dec;6(12 Suppl):S12-7. doi: 10.1016/j.hrthm.2009.07.026. Epub 2009 Oct 23. Review.

Hussein AA, Martin DO, Saliba W, Patel D, Karim S, Batal O, Banna M, Williams-Andrews M, Sherman M, Kanj M, Bhargava M, Dresing T, Callahan T, Tchou P, Di Biase L, Beheiry S, Lindsay B, Natale A, Wazni O. Radiofrequency ablation of atrial fibrillation under therapeutic international normalized ratio: a safe and efficacious periprocedural anticoagulation strategy. Heart Rhythm. 2009 Oct;6(10):1425-9. doi: 10.1016/j.hrthm.2009.07.007. Epub 2009 Jul 10.

Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber DJ, Ma CS, Hess S, Wells DS, Juang G, Vijgen J, Hügl BJ, Balasubramaniam R, De Chillou C, Davies DW, Fields LE, Natale A; VENTURE-AF Investigators. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J. 2015 Jul 21;36(28):1805-11. doi: 10.1093/eurheartj/ehv177. Epub 2015 May 14.

Chen J, Todd DM, Hocini M, Larsen TB, Bongiorni MG, Blomström-Lundqvist C; Scientific Initiative Committee, European Heart Rhythm Association. Current periprocedural management of ablation for atrial fibrillation in Europe: results of the European Heart Rhythm Association survey. Europace. 2014 Mar;16(3):378-81. doi: 10.1093/europace/euu043.

Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390.

Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Natale A, Packer D, Skanes A, Ambrogi F, Biganzoli E. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010 Feb;3(1):32-8. doi: 10.1161/CIRCEP.109.859116. Epub 2009 Dec 7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hohnloser SH, Camm J, Cappato R, Diener HC, Heidbuchel H, Lanz HJ, Mont L, Morillo CA, Smolnik R, Yin OQP, Kautzner J. Uninterrupted administration of edoxaban vs vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation: Rationale and design of the ELIMINATE-AF study. Clin Cardiol. 2018 Apr;41(4):440-449. doi: 10.1002/clc.22918. Epub 2018 Apr 17.

Responsible Party:	Daiichi Sankyo Europe, GmbH
ClinicalTrials.gov Identifier:	NCT02942576 History of Changes
Other Study ID Numbers:	DSE-EDO-01-16-EU; 2016-003069-25 ( EudraCT Number )
First Posted:	October 24, 2016
Last Update Posted:	March 1, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials:	Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
Time Frame:	Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
Access Criteria:	Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL:	https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Edoxaban; Phenprocoumon; Acenocoumarol	Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants