Clinical trial NCT02942576: Edoxaban Treatment Versus Vitamin K Antagonist (VKA) in Patients With Atrial Fibrillation (AF) Undergoing Catheter Ablation
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2016-10-24
Enrollment: 632
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 International Society on Thrombosis and Hemostasis (ISTH), or conditions associated with high risk of bleeding
* Subjects with any contraindication for anticoagulant agents.

Primary outcomes:
measure: Number of Participants Who Experienced the Composite of All-cause Death, Stroke (VARC-2), and Major Bleeding (ISTH) in the Edoxaban Group Compared With Vitamin K Antagonist (VKA) Group in Participants Undergoing Catheter Ablation (Adjudicated Data)
timeFrame: Day 1 to Day 90
measure: Number of Participants Who Experienced Major Bleeding (International Society on Thrombosis and Hemostasis [ISTH]) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
timeFrame: Day 1 to Day 90
Secondary outcomes:
measure: Number of Participants Who Experienced the Composite of All-cause Death, Stroke (Alternative), and Major Bleeding (ISTH) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
timeFrame: Day 1 to Day 90
measure: Number of Participants Who Experienced the Composite of Stroke (VARC-2), Systemic Embolic Events (SEE), and Cardiovascular (CV) Mortality in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
timeFrame: Day 1 to Day 90
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: Erasme Hospital
city: Brussels
country: Belgium
facility: UZ Brussel
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Calgary
country: Canada
facility: University of Calgary
city: Hamilton
country: Canada
facility: Hamilton Health Sciences/McMaster University
city: Montréal
country: Canada
facility: Montreal Heart Institute
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
city: Brno
country: Czechia
facility: FN Brno
city: Brno
country: Czechia
facility: St. Anne's University Hospital Brno, International Clinical Research Center
city: Prague
country: Czechia
facility: IKEM
city: Prague
country: Czechia
facility: University Hospital Motol - Cardiology
city: Praha
country: Czechia
facility: FN Kralovske Vinohrady
city: Praha
country: Czechia
facility: VFN v Praze II. Interní klinika - Kardiologie a angiologie
city: Ústí nad Labem
country: Czechia
facility: Masarykova nemocnice - Kardiologie Krajská zdravotní, a.s.
city: Bad Krozingen
country: Germany
facility: Universitäts Herzzentrum Freiburg-Bad Krozingen Klinik für Kardiologie und Angiologie II
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin - CVK Medizinische Klinik m.S. Kardiologie
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld Klinik für Kardiologie/internist. Intensivmedizin
city: Coburg
country: Germany
facility: Klinikum Coburg GmbH II.Med.Klinik
city: Dortmund
country: Germany
facility: Klinik für Innere Medizin I
city: Duesseldorf
country: Germany
facility: University Clinic Duesseldorf Clinic for Cardiology, Pneumology and Angiology
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg Kardiologie mit Schwerpunkt Elektrophysiologie
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg Clinic of Cardiology, Angiology and Pneumology
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig - Universitätsklinik Abteilung für Rhythmologie
city: Muenster
country: Germany
facility: Univ. of Muenster.Cardiovascular Medicine
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock Zentrum für Innere Medizin I, Kardiologie
city: Tübingen
country: Germany
facility: Deutsches Herzk. Universitätsklinikum Tübingen Medizinische Klinik III. Kardiologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wuerzburg
country: Germany
facility: Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ Kardiológiai Osztály
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika
city: Pécs
country: Hungary
facility: Pecs University Clinical Center
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem II. Belgyógyászati Klnika és Kardiológiai Központ
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház Kardiológia Osztály
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Castel Volturno
country: Italy
facility: Pineta Grande Hospital
city: Catanzaro
country: Italy
facility: Universita' degli Studi Catanzaro
city: Cona
country: Italy
facility: Arcispedale Sant'Anna
city: Firenze
country: Italy
facility: Azienda USL Toscana
city: Grosseto
country: Italy
facility: Ospedale della Misericordia
city: Mestre
country: Italy
facility: Ospedale dell'Angelo
city: Monza
country: Italy
facility: ASST Vimercate
city: Negrar
country: Italy
facility: Ospedale Santo Cuore
city: Pavia
country: Italy
facility: Istituto di Cura cittè di Pavia
city: Piacenza
country: Italy
facility: Azienda Ospedaliera di Piacenza "Ospedale Guglielmo d Saliceto"
city: Roma
country: Italy
facility: Policlinico Casilino
city: Rome
country: Italy
facility: Largo Agostino Gemelli
city: Sant'Eramo
country: Italy
facility: Ospedale Ecclesiastico "Miulli"
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Hospital
state: Seodaemun-Gu
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Seoungbuk-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Kraków
country: Poland
facility: University Hospital - Szpital Uniwersytecki
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 Klinika Kardiologii
city: Warszawa
country: Poland
facility: Oddzial Kardiologii Szpital Grochowski im. dr R. Masztaka SPZOZ
city: Zabrze
country: Poland
facility: Oddział Kliniczny Kardiologii SUM Katedra Kardiologii
city: Łódź
country: Poland
facility: Klinika Intensywnej Terapii Kardiologicznej
city: Alicante
country: Spain
facility: Hospital General Universitario
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic Cardiologia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: San Juan de Alicante
country: Spain
facility: Hospital Universitario San Juan de Alicante
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital (VGH-TC)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Trust
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: King's College Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
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citation: Chen J, Todd DM, Hocini M, Larsen TB, Bongiorni MG, Blomstrom-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.
citation: Hokusai-VTE Investigators; Buller HR, Decousus 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.
citation: 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.
citation: Hohnloser SH, Camm AJ, Cappato R, Diener HC, Heidbuchel H, Mont L, Morillo CA, Lanz HJ, Rauer H, Reimitz PE, Smolnik R, Kautzner J. Periprocedural anticoagulation in the uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation (ELIMINATE-AF) trial. Europace. 2021 Jan 27;23(1):65-72. doi: 10.1093/europace/euaa199.
citation: 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.