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

Phase 3
Completed
Conditions
Atrial Fibrillation
Interventions
Drug: VKA-Based Regimen
Registration Number
NCT02942576
Lead Sponsor
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
632
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Edoxaban-based regimenEdoxabanEdoxaban-based regimen for 21 days pre- and 90 days post-ablation period.
VKA-based regimenVKA-Based RegimenVKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)
Primary Outcome Measures
NameTimeMethod
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)Day 1 to Day 90

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.

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)Day 1 to Day 90

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.

Secondary Outcome Measures
NameTimeMethod
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

An alternative definition characterized stroke (ischemic, hemorrhagic, or undetermined) as an abrupt onset, over minutes to hours, of a focal neurological deficit in the distribution of a single brain artery that was not due to an identifiable nonvascular cause (ie, brain tumor or trauma), and that either lasted at least 24 hours or resulted in death within 24 hours of onset.

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.

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

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.

SEE was defined as an arterial embolism resulting in clinical ischemia, excluding the central nervous system, coronary, and pulmonary arterial circulation.

CV mortality was defined as cardiac or vascular death according to Academic Research Consortium.

Trial Locations

Locations (74)

Klinika Intensywnej Terapii Kardiologicznej

🇵🇱

Łódź, Poland

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

Seoul National University Hospital

🇰🇷

Seoul, Jongno-gu, Korea, Republic of

Pineta Grande Hospital

🇮🇹

Castel Volturno, Italy

Ospedale dell'Angelo

🇮🇹

Mestre, Italy

Istituto di Cura cittè di Pavia

🇮🇹

Pavia, Italy

Deutsches Herzk. Universitätsklinikum Tübingen Medizinische Klinik III. Kardiologie

🇩🇪

Tübingen, Germany

Korea University Anam Hospital

🇰🇷

Seoul, Seoungbuk-gu, Korea, Republic of

Pecs University Clinical Center

🇭🇺

Pécs, Hungary

Ospedale San Donato

🇮🇹

Arezzo, Italy

Azienda Ospedaliera di Piacenza "Ospedale Guglielmo d Saliceto"

🇮🇹

Piacenza, Italy

Hospital Universitario San Juan de Alicante

🇪🇸

San Juan de Alicante, Spain

Universitätsklinikum Ulm

🇩🇪

Ulm, Germany

FN Brno

🇨🇿

Brno, Czechia

Samsung Medical Center

🇰🇷

Seoul, Gangnam-gu, Korea, Republic of

IKEM

🇨🇿

Prague, Czechia

University Hospital Motol - Cardiology

🇨🇿

Prague, Czechia

ASST Vimercate

🇮🇹

Monza, Italy

Ospedale Ecclesiastico "Miulli"

🇮🇹

Sant'Eramo, Italy

Klinikum Coburg GmbH II.Med.Klinik

🇩🇪

Coburg, Germany

Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I

🇩🇪

Wuerzburg, Germany

Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika

🇭🇺

Debrecen, Hungary

Szegedi Tudományegyetem II. Belgyógyászati Klnika és Kardiológiai Központ

🇭🇺

Szeged, Hungary

Zala Megyei Szent Rafael Kórház Kardiológia Osztály

🇭🇺

Zalaegerszeg, Hungary

Oddział Kliniczny Kardiologii SUM Katedra Kardiologii

🇵🇱

Zabrze, Poland

Taichung Veterans General Hospital (VGH-TC)

🇨🇳

Taichung City, Taiwan

FN Kralovske Vinohrady

🇨🇿

Praha, Czechia

VFN v Praze II. Interní klinika - Kardiologie a angiologie

🇨🇿

Praha, Czechia

Royal Bournemouth Hospital

🇬🇧

Bournemouth, United Kingdom

Policlinico Casilino

🇮🇹

Roma, Italy

University Clinic Duesseldorf Clinic for Cardiology, Pneumology and Angiology

🇩🇪

Duesseldorf, Germany

Arcispedale Sant'Anna

🇮🇹

Cona, Italy

University of Calgary

🇨🇦

Calgary, Canada

University Hospital - Szpital Uniwersytecki

🇵🇱

Kraków, Poland

Oddzial Kardiologii Szpital Grochowski im. dr R. Masztaka SPZOZ

🇵🇱

Warszawa, Poland

Hospital General Universitario

🇪🇸

Alicante, Spain

University Hospital of Heidelberg Clinic of Cardiology, Angiology and Pneumology

🇩🇪

Heidelberg, Germany

Herzzentrum Leipzig - Universitätsklinik Abteilung für Rhythmologie

🇩🇪

Leipzig, Germany

Universita' degli Studi Catanzaro

🇮🇹

Catanzaro, Italy

Azienda USL Toscana

🇮🇹

Firenze, Italy

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

🇩🇪

Berlin, Germany

Montreal Heart Institute

🇨🇦

Montréal, Canada

Ospedale della Misericordia

🇮🇹

Grosseto, Italy

Ospedale Santo Cuore

🇮🇹

Negrar, Italy

Samodzielny Publiczny Szpital Kliniczny Nr 4 Klinika Kardiologii

🇵🇱

Lublin, Poland

Blackpool Teaching Hospitals NHS

🇬🇧

Blackpool, United Kingdom

Nottingham City Hospital

🇬🇧

Nottingham, United Kingdom

Hospital Clinic Cardiologia

🇪🇸

Barcelona, Spain

Yonsei University Severance Hospital

🇰🇷

Seoul, Seodaemun-Gu, Korea, Republic of

Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Papworth Hospital NHS Trust

🇬🇧

Cambridge, United Kingdom

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Leeds General Infirmary

🇬🇧

Leeds, United Kingdom

Universitätsmedizin Rostock Zentrum für Innere Medizin I, Kardiologie

🇩🇪

Rostock, Germany

Erasme Hospital

🇧🇪

Brussels, Belgium

ZNA Middelheim

🇧🇪

Antwerpen, Belgium

Hamilton Health Sciences/McMaster University

🇨🇦

Hamilton, Canada

UZ Brussel

🇧🇪

Brussels, Belgium

Centre Hospitalier Universitaire de Sherbrooke

🇨🇦

Sherbrooke, Canada

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

🇩🇪

Bad Krozingen, Germany

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

🇨🇿

Brno, Czechia

Masarykova nemocnice - Kardiologie Krajská zdravotní, a.s.

🇨🇿

Ústí nad Labem, Czechia

Klinikum Bielefeld Klinik für Kardiologie/internist. Intensivmedizin

🇩🇪

Bielefeld, Germany

Klinik für Innere Medizin I

🇩🇪

Dortmund, Germany

Universitäres Herzzentrum Hamburg Kardiologie mit Schwerpunkt Elektrophysiologie

🇩🇪

Hamburg, Germany

Univ. of Muenster.Cardiovascular Medicine

🇩🇪

Muenster, Germany

Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika

🇭🇺

Budapest, Hungary

Magyar Honvédség Egészségügyi Központ Kardiológiai Osztály

🇭🇺

Budapest, Hungary

Largo Agostino Gemelli

🇮🇹

Rome, Italy

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Hospital del Mar

🇪🇸

Barcelona, Spain

Chang Gung Memorial Hospital

🇨🇳

Taoyuan City, Taiwan

China Medical University Hospital

🇨🇳

Taichung City, Taiwan

King's College Hospital

🇬🇧

London, United Kingdom

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