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

NCT02942576 | Completed Phase 3 Results DMC

• 2 other identifiers: DSE-EDO-01-16-EU2016-003069-25
• Study Type: interventional
• Target: 632
• Locations: 11 countries
• Sites: 75

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.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• 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)

  Stroke (ischemic, hemorrhagic, or undetermined) was defined by Valve Academic Research Consortium-2 (VARC-2) as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury following hemorrhage or infarction. A stroke event was based on any of the following: duration of neurological dysfunction \>24 hours (h), duration of neurological dysfunction \<24 h in case of imaging-documented new hemorrhage or infarction, and a neurological dysfunction resulting in death. Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of \>2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability.

  Day 1 to Day 90

• 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)

  Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of \>2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability.

  Day 1 to Day 90

Secondary Outcomes (2)

• 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)

  Day 1 to Day 90

• 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)

  Day 1 to Day 90

Study Arms (2)

Edoxaban-based regimen

EXPERIMENTAL

Edoxaban-based regimen for 21 days pre- and 90 days post-ablation period.

Drug: Edoxaban

VKA-based regimen

ACTIVE COMPARATOR

VKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)

Drug: VKA-Based Regimen

Interventions

Edoxaban DRUG

Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects.

Also known as: Lixiana

Edoxaban-based regimen

VKA-Based Regimen DRUG

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, United Kingdom (UK), Taiwan and Korea.

Also known as: Warfarin

VKA-based regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: lead

Study Sites (75)

ZNA Middelheim

Antwerp, 2020, Belgium

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

University of Calgary

Calgary, T2N 4Z6, Canada

Location

Hamilton Health Sciences/McMaster University

Hamilton, L8L 2X2, Canada

Location

Montreal Heart Institute

Montreal, H1T 1C8, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, J1H 5N4, Canada

Location

FN Brno

Brno, 625 00, Czechia

Location

St. Anne's University Hospital Brno, International Clinical Research Center

Brno, 69691, Czechia

Location

FN Kralovske Vinohrady

Prague, 100 34, Czechia

Location

VFN v Praze II. Interní klinika - Kardiologie a angiologie

Prague, 128 08, Czechia

Location

IKEM

Prague, 14021, Czechia

Location

University Hospital Motol - Cardiology

Prague, 150 06, Czechia

Location

Masarykova nemocnice - Kardiologie Krajská zdravotní, a.s.

Ústí nad Labem, 40113, Czechia

Location

Universitäts Herzzentrum Freiburg-Bad Krozingen Klinik für Kardiologie und Angiologie II

Bad Krozingen, 79189, Germany

Location

Charité Universitätsmedizin Berlin - CVK Medizinische Klinik m.S. Kardiologie

Berlin, 13353, Germany

Location

Klinikum Bielefeld Klinik für Kardiologie/internist. Intensivmedizin

Bielefeld, 33604, Germany

Location

Klinikum Coburg GmbH II.Med.Klinik

Coburg, 96450, Germany

Location

Klinik für Innere Medizin I

Dortmund, 44137, Germany

Location

University Clinic Duesseldorf Clinic for Cardiology, Pneumology and Angiology

Düsseldorf, 40225, Germany

Location

Universitäres Herzzentrum Hamburg Kardiologie mit Schwerpunkt Elektrophysiologie

Hamburg, 20251, Germany

Location

University Hospital of Heidelberg Clinic of Cardiology, Angiology and Pneumology

Heidelberg, 69120, Germany

Location

Herzzentrum Leipzig - Universitätsklinik Abteilung für Rhythmologie

Leipzig, 04289, Germany

Location

Univ. of Muenster.Cardiovascular Medicine

Münster, 48149, Germany

Location

Universitätsmedizin Rostock Zentrum für Innere Medizin I, Kardiologie

Rostock, 18057, Germany

Location

Deutsches Herzk. Universitätsklinikum Tübingen Medizinische Klinik III. Kardiologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I

Würzburg, 97080, Germany

Location

Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika

Budapest, 1122, Hungary

Location

Magyar Honvédség Egészségügyi Központ Kardiológiai Osztály

Budapest, 1134, Hungary

Location

Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika

Debrecen, 4032, Hungary

Location

Pecs University Clinical Center

Pécs, H 7624, Hungary

Location

Szegedi Tudományegyetem II. Belgyógyászati Klnika és Kardiológiai Központ

Szeged, 6725, Hungary

Location

Zala Megyei Szent Rafael Kórház Kardiológia Osztály

Zalaegerszeg, 8900, Hungary

Location

Ospedale San Donato

Arezzo, 52100, Italy

Location

Pineta Grande Hospital

Castel Volturno, 81030, Italy

Location

Universita' degli Studi Catanzaro

Catanzaro, 88100, Italy

Location

Arcispedale Sant'Anna

Cona, 44124, Italy

Location

Azienda USL Toscana

Florence, 50122, Italy

Location

Ospedale della Misericordia

Grosseto, 58100, Italy

Location

Ospedale dell'Angelo

Mestre, 30174, Italy

Location

ASST Vimercate

Monza, 80082, Italy

Location

Ospedale Santo Cuore

Negrar, 37024, Italy

Location

Istituto di Cura cittè di Pavia

Pavia, 27100, Italy

Location

Azienda Ospedaliera di Piacenza "Ospedale Guglielmo d Saliceto"

Piacenza, 29124, Italy

Location

Policlinico Casilino

Roma, 00169, Italy

Location

Largo Agostino Gemelli

Rome, 00168, Italy

Location

Ospedale Ecclesiastico "Miulli"

Sant'Eramo, 70021, Italy

Location

University Hospital - Szpital Uniwersytecki

Krakow, 31-501, Poland

Location

Klinika Intensywnej Terapii Kardiologicznej

Lodz, 92-213, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 4 Klinika Kardiologii

Lublin, 20-954, Poland

Location

Oddzial Kardiologii Szpital Grochowski im. dr R. Masztaka SPZOZ

Warsaw, 04-073, Poland

Location

Oddział Kliniczny Kardiologii SUM Katedra Kardiologii

Zabrze, 41-800, Poland

Location

Samsung Medical Center

Seoul, Gangnam-gu, 06351, South Korea

Location

Seoul National University Hospital

Seoul, Jongno-gu, 03080, South Korea

Location

Yonsei University Severance Hospital

Seoul, Seodaemun-Gu, 03722, South Korea

Location

Korea University Anam Hospital

Seoul, Seoungbuk-gu, 02841, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital General Universitario

Alicante, 03540, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic Cardiologia

Barcelona, 8036, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario San Juan de Alicante

Sant Joan d'Alacant, 03550, Spain

Location

Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital (VGH-TC)

Taichung, 40705, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan, 33305, Taiwan

Location

Blackpool Teaching Hospitals NHS

Blackpool, FY3 8NR, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Papworth Hospital NHS Trust

Cambridge, CB23 3RE, United Kingdom

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (10)

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• 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.

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  PMID: 25975659 BACKGROUND

• 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.

  PMID: 24569891 BACKGROUND

• 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.

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MeSH Terms

Conditions

Atrial Fibrillation

Interventions

edoxaban; Warfarin; Phenprocoumon; fluindione; Acenocoumarol

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Daiichi Sankyo
• Organization: Contact for Clinical Trial Information

CTRinfo@dsi.com

1-908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 24, 2016
• Study Start: March 21, 2017
• Primary Completion: September 24, 2018
• Study Completion: September 24, 2018
• Last Updated: September 23, 2019
• Results First Posted: September 23, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU), US and/or Japan 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, the European Union or Japan 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.

Locations

TW (5); PL (5); KR (5); ES (5); BE (4); DE (14); CA (4); GB (6); CZ (7); HU (6); IT (14)