Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ENTRUST-AF-PCI)
Atrial Fibrillation
About this trial
This is an interventional treatment trial for Atrial Fibrillation focused on measuring percutaneous intervention, vitamin K antagonist
Eligibility Criteria
Inclusion Criteria:
- Oral anticoagulant (OAC) indication for atrial fibrillation for a period of at least 12 months following successful PCI with stenting.
Eligibility is assessed 4 hours after sheath removal and within 5 days after successful PCI with stent placement. If a staged PCI is planned, eligibility is assessed after completion of the last stage.
Successful PCI definition:
The success of a PCI procedure is defined by 2 interrelated components: angiographic findings, procedural / clinical outcomes as detailed below:
Angiographic Success A minimum stenosis diameter of < 20% (as visually assessed by angiography - residual blockage or stenosis reduced to less than 20% of the artery's diameter).
Sufficient enlargement of the lumen at the target site to improve coronary artery blood flow with final thrombolysis in myocardial infarction (TIMI) flow grade 3 (visually assessed by angiography), without occlusion of a significant side branch, flow-limiting dissection, distal embolization, or angiographic thrombus.
Procedural Success No major in-hospital clinical complications(e.g. ongoing International Society on Thrombosis and Haemostasis [ISTH] major or clinical relevant non-major procedural bleeding at the time of randomization, stroke, emergency coronary artery bypass graft [CABG]).
In summary, a clinically successful PCI requires both anatomic and procedural success along with relief of signs and/or symptoms of myocardial ischemia at the time of randomization.
Exclusion Criteria:
- Bleeding risks or systemic conditions
Known bleeding diathesis, including but not limited to,
Uncontrolled active bleeding, encompassing both ISTH major and clinically relevant non-major bleeding, preceding randomization.
Lesion or condition, if considered to be a significant risk for major bleeding. This may include but is not limited to: unresolved gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding (e.g. malignancies with metastasis), recent unresolved brain or spinal injury, recent brain, spinal or ophthalmic surgery, any intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms (of more than 3.5 cm) or major intraspinal or intracerebral vascular abnormalities.
- Medication-related
- International normalized ratio (INR) > 2.5 (the participant can be reconsidered at a later time, but within 5 days of sheath removal).
- Contraindication to edoxaban, VKA, acetylsalicylic acid (ASA) and/or P2Y12 antagonists;
- Concomitant treatment with other antithrombotic agents, fibrinolytic therapy and chronic nonsteroidal anti-inflammatory drugs (NSAIDs).
Concomitant conditions and therapies
Critically ill or hemodynamically unstable subjects (at the time of randomization) including:
- cardiogenic shock or acute decompensated heart failure, with the requirement for vasopressor agents or inotropic support or mechanical support to support circulation
- respiratory failure requiring endotracheal intubation and mechanical ventilation.
- Any prior mechanical valvular prosthesis;
- Planned coronary or vascular intervention or major surgery within 12 months; Randomization must be deferred to the last stage in a multistep, multivessel PCI procedure;
- Moderate or severe mitral stenosis;
- Ischemic stroke within 2 weeks prior to randomization;
- Uncontrolled severe hypertension with a systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥ 120 mmHg;
- End stage renal disease (ESRD) (CrCL < 15 mL/min or on dialysis);
- Known abnormal liver function prior to randomization (including hepatic disease or biochemical evidence of significant liver derangement known prior to randomization).
Other exclusion criteria
Any of the following abnormal local laboratory results prior to randomization:
- Platelet count < 50 x10^9/L
- Hemoglobin < 8 mg/dL
- Unable to provide written Informed Consent;
- Female participants of childbearing potential without using highly effective contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include: Combined (estrogen and progestogen containing) oral, intravaginal, transdermal, hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence;
- Pregnant or breast-feeding participants;
- Assessment that the participant is not likely to comply with the study procedures or have complete follow-up;
- Participating in another clinical trial that potentially interferes with the current study;
- Previous randomization in this study;
- Active on prescription drug abuse and addiction; abuse of illicit substances (i.e. marijuana, cocaine, methamphetamine, heroin) and alcohol abuses during the last 12 months according to the judgement of the investigator;
- Life expectancy < 12 months.
Sites / Locations
- Medizinische Universitaetsklinik Graz
- University Hospital Innsbruck
- Krankenhaus Hietzing
- Wilhelminenspital
- ASZ Aalst
- Imelda Ziekenhuis
- AZ St Jan
- Hopital Erasme
- University Hospital Antwerp
- Virga Jesse Jessa hospital
- AZ Delta
- University Hospital of Angers
- Hopital Cote Basque
- Chru Jean Minjoz
- Metropole Savoie Hospital
- Centre Hospitalier Sud Francilien
- Hospital Henri Mondor
- CHU de Nice
- Hôpital Bichat - Claude Bernard
- Hôpital Rangueil, Service Cancérologie
- Clinique Vauban
- University Hospital Aachen
- Universitäts-Herzzentrum Freiburg • Bad Krozingen
- Kerckhoff Klinik
- Vivantes Klinikum im Friedrichshaim
- Charité Benjamin Franklin
- Charité, Campus Virchow-Klinikum - Medizinische Klinik mit Schwerpunkt Kardiologie
- Staedtische Kliniken Bielefeld
- GFO Kliniken Bonn - St.-Marien-Hospital
- Universitätsklinikum Bonn - Medizinische Klinik II - Innere Medizin (Kardiologie, Angiologie und Pneumologie)
- Klinikum Coburg Med. Klinik Kardiologie, Angiologie, Pneumologie
- St. Johannes- Hospital
- Heinrich-Heine-Universität Düsseldorf - Universitätsklinikum Düsseldorf (UKD) Klinik für Kardiologie, Pneumologie und Angiologie
- Universitaetsklinikum Freiburg Klinik für Kardiologie und Angiologie I
- Universitäres Herzzentrum Hamburg GmbH (UHZ)
- Universitätsklinikum Heidelberg Klinik für Kardiologie, Angiologie und Pneumologie (Innere Medizin III)
- Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin
- Universitätsklinikum Jena Klinik für Innere Medizin I, Kardiologie, Angiologie, Pneumologie, Internistische Intensivmedizin
- Herzzentrum Leipzig - Universitätsklinik Klinik für Innere Medizin/Kardiologie
- Klinikum Ludwigshafen
- Städtisches Klinikum Lüneburg
- Kliniken Maria Hilf GmbH
- Klinik Dr. Müller GmbH & Co. KG, Peter Osypka Herzzentrum
- Universitätsklinikum Münster - Department für Kardiologie und Angiologie
- St. Vincenz-Krankenhaus Paderborn - Medizinische Klinik II
- Universitätsmedizin Rostock
- Universitäts Klinikum Tübingen
- Herzklinik Ulm
- Universitätsklinik Ulm - Zentrum für Innere Medizin - Klinik für Innere Medizin II
- Schwarzwald-Baar Klinikum - Kliniken Villingen-Schwenningen - Innere Medizin III: Kardiologie und Intensivmedizin
- St. Josefs-Hospital - Medizinische Klinik I, Kardiologie
- HELIOS Klinikum Wuppertal - Herzzentrum
- Állami Szívkórház
- Budai Irgalmasrendi Kht.
- Gottsegen György Országos Kardiológiai Intézet
- Bajcsy-Zsilinszky Kórház és Rendelőintézet
- Magyar Honvédség Egészségügyi Központ
- Debreceni Egyetem Klinikai Központ
- Békés Megyei Központi Kórház
- Petz Aladar Megyei Oktato Korhaz
- Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház, Jósa András Oktatókórház
- Pécsi Tudományegyetem
- Szegedi Tudományegyetem
- Fejér Megyei Szent György Egyetemi Oktató Kórház
- Ospedale San Donato- ASL 8 Arezzo
- Policlinico di Bari
- Ospedale Maggiore C.A. Pizzardi -OR - Laboratorio di Cardiologia Interventistica
- AOU Materdomini, Magna Graecia University
- ASL2 Chieti - SS Maria Annunziata
- A.S.O.S. Croce e Carle Cuneo
- AOU Sant'Anna
- Ospedale Careggi
- Ospedali Riuniti di Foggia
- Ospedale Alessandro Manzoni-Azienda Ospedaliera di Lecco
- Asst Fatebenefratelli-Sacco
- AOU Policlinico di Modena
- University Hospital Federico II
- Padova University Hospital
- Azienda Ospedaliero-Universitaria di Parma
- Ospedale degli Infermi
- Ospedale degli Infermi di Rivoli
- Policlinico Agostino Gemelli
- S.Camillo Forlanini - Ospedale S.Camillo Reparto di Emodinamica
- Bolognini Hospital Seriate
- "Santa Maria" University Hospital - Azienda Ospedaliera Santa Maria Di Terni
- U.O. Cardiologia Ospedale Borgo Trento
- Pusan National University Hospital
- Daegu Catholic University Hospital
- Chonnam National University Hospital
- Inje Univ. Ilsan Paik Hospital
- The Catholic University of Korea St.Vincent's Hospital
- Hallym University Sacred Heart Hospital
- Inha University Hospital
- Chonbuk National University Hospital
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Severance Hospital
- Samsung Medical Centre
- SEOUL St.Maria
- Boramae Medical Center
- Korea University Guro Hospital
- Korea University Anam Hospital
- Lithuanian University of Health Sciences hospital
- Klaipeda Seamen's Hospital
- Vilnius University Hospital "Santariskiu Clinic"
- Republican Siauliai Hospital
- St Antonius Hospital
- Radboud university medical center
- Maasstad Hospital
- MC Haaglanden
- II Oddział Kardiologiczny, Polsko-Amerykanskie Kliniki Serca
- MCSN AHoP
- III Oddział Kardiologii Inwazyjnej, Angiologii i Elektrokardiologii Polsko-Amerykanskie Kliniki Serca
- Krakowski Szpital Specjalistyczny im. Jana Pawła II, Oddział Kliniczny Kardiologii Interwencyjnej z Pododdziałem Intenyswengo Nadzoru Kardiologicznego
- AHP IV DEP K-Kozle
- Nyskie Centrum Sercowo-Naczyniowe, Polsko-Amerykanskie Kliniki Serca
- Clin-Medica OMC sp. z o.o. s.k.
- X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji Polsko-Amerykanskie Kliniki Serca
- Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego; Klinika Kardiologii i Angiologii Interwencyjnej
- Instytut Kardiologii im. Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego, Klinika Choroby Wieńcowej i Strukturalnych Chorób Serca
- Nzoz Salus
- Hospital Garcia de Orta, EPE
- Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz
- Centro Hospitalar e Universitário de Coimbra, EPE
- Centro Hospitalar e Universitário de Coimbra, EPE - Hospital dos Covões
- Centro Hospitalar de Lisboa Central, EPE - Hospital Santa Marta
- Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
- Emergency County Hospital Baia Mare
- "Prof. C.C. Iliescu" Emergency Institute for Cardiovascular Diseases
- University Hospital of Bucharest
- Saint John Emergency Hospital
- Oradea Emergency County Clinical Hospital
- Institutul de Boli Cardiovasculare Timisoara
- Emergency Institute of Cardiovascular Diseases and Transplantation
- Clinical Center of Serbia
- Clinical Hospital Center -Zvezdara
- Institute of CV Diseases Clinical Center of Serbia
- Clinical Center Kragujevac
- Institute of Cardiovascular Diseases of Vojvodina
- General University Hospital of Alicante
- Hospital Universitari Germans Trias i Pujol
- Complejo Hospitalario Universitario de Granada
- Bellvitge University Hospital
- Complejo Asistencial Universitario de León
- Hospital Ramon y Cajal
- Clinica Universitaria San Carlos
- Hospital La Paz, Madrid
- Hospital Universitario 12 de Octubre
- Hospital Universitario Puerta de Hierro
- Hospital Universitario Virgen de la Arrixaca
- Hospital Universitario Virgen de La Victoria
- Hospital Universitario de Salamanca
- Hospital Universitari i Politècnic La Fe
- Hospital Clínico Universitario de Valladolid
- Hospital Álvaro Cunqueiro
- HFR Freiburg - Kantonsspital Kardiologie
- Cardiocentro Ticino
- Hsinchu Mackay Memorial Hospital (HMMH)
- Kaohsiung medical University Chung-Ho Memorial Hospital (KMUH)
- E-DA Hospital
- Far Eastern Memorial Hospital (FEMH)
- China Medical University Hospital (CMUH)
- Chi-Mei Medical Center (CMMC)
- National Cheng Kung University Hospital
- Cheng Hsin General Hospital
- Taipei Veterans General Hospital
- Chang-Gung Memorial Hospital
- Cherkasy regional cardiological center
- Chernihiv City Hospital #2
- Chernivtsi Regional Clinical Cardiology Dispensary
- CI "Dnipropetrovsk Joint Emergency Hospital"
- Communal Institution Dnepropetrovsk Regional Diagnostic Center
- Ivano-Frankivsk Central City Clinical Hospital
- L.T. Malaya Therapy National Institute of the National Academy of medical science of Ukraine
- Communal Health Care Institution "Regional Clinical Hospital - Center of Emergency Medical Care and Disaster Medicine"
- Kharkiv City Clinical Hospital #8
- Kharkiv Railway Clinical Hospital N1 of Brance "Health Center" of the Public joint stock company "Ukrainian Railway"
- Khmelnytskyy regional hospital
- Insititute of Heart of MoH Ukraine
- Kyiv City Clinical Hospital#5
- State Institution 'National Scientific Central Institute of Cardiology named after MD Strazhesko'
- Kyiv City Clinical Hospital 4
- Oleksandrivska Kiyv City Clinical Hospital
- Communal Institution of Kyiv Regional Rada
- Lviv Regional State Clinical Treatment and Diagnostic Cardiology Center
- Lutsk City Hospital
- Nikolaev Regional Clinical Hospital
- Odessa Regional Hospital, Cardiosurgery Center
- Communal Institution Rivne Regional Clinical Hospital
- Communal Institution of Sumy Regional Rada
- Transcarpathian Regional Clinical Cardiology Clinic
- Communal Institution "Vinnytsia Regional Diagnostic Center of cardiovascular disease"
- Vinnytsya Regional Clinical Hospital n.a. Pyrogov
- Zaporizhzhia Regional cardiology dispensary
- Blackpool Victoria Hospital
- University Hospital of Wales
- Golden Jubilee Hospital
- Royal Infirmary of Edinburgh
- Altnagelvin Area Hospital
- Southern Health and Social Care Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Edoxaban Regimen
Vitamin K Antagonist Regimen
Participants will be randomized to receive edoxaban 60 mg once-daily or 30 mg once-daily and clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel [5 mg or 10 mg once-daily] or ticagrelor [90 mg twice-daily] may be used) used.
Participants will be randomized to receive VKA in combination with clopidogrel 75 mg once-daily (or in the presence of a documented clinical need prasugrel [5mg or 10 mg once-daily] or ticagrelor [90 mg twice-daily] may be used) and aspirin (100 mg once-daily, for a minimum of 1 month and up to 12 months duration.