Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ENTRUST-AF-PCI)

Evaluation of the Safety and Efficacy of an Edoxaban-based Compared to a Vitamin K Antagonist-based Antithrombotic Regimen in Subjects With Atrial Fibrillation Following Successful Percutaneous Coronary Intervention (PCI) With Stent Placement.

There are insufficient data on the safety and efficacy of edoxaban plus antiplatelet therapy in subjects with atrial fibrillation (AF) following percutaneous intervention (PCI) with stenting. This study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a vitamin K antagonist (VKA)-based antithrombotic regimen in subjects with AF following PCI with stent placement. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Edoxaban; Drug: Clopidogrel; Drug: Prasugrel; Drug: Ticagrelor; Drug: Vitamin K antagonist

• Study Type: Interventional
• Enrollment (Actual): 1506
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaetsklinik Graz
  • Innsbruck, Austria, 6020
    • University Hospital Innsbruck
  • Wien, Austria, 1130
    • Krankenhaus Hietzing
  • Wien, Austria, 1160
    • Wilhelminenspital
• Belgium
  • Aalst, Belgium, 9300
    • ASZ Aalst
  • Bonheiden, Belgium, 2820
    • Imelda Ziekenhuis
  • Brugge, Belgium, 8000
    • AZ St Jan
  • Brussel, Belgium, 1070
    • Hopital Erasme
  • Edegem, Belgium, 2650
    • University Hospital Antwerp
  • Hasselt, Belgium, 3500
    • Virga Jesse Jessa hospital
  • Roeselare, Belgium, 8800
    • AZ DELTA
• France
  • Angers, France, 49933
    • University Hospital of Angers
  • Bayonne, France, 64100
    • Hopital Cote Basque
  • Besancon, France, 25030
    • CHRU Jean Minjoz
  • Chambery, France, 73000
    • Métropole Savoie Hospital
  • Corbeil Essonnes Cedex, France, 91106
    • Centre Hospitalier Sud Francilien
  • Creteil, France, 94000
    • Hospital Henri Mondor
  • Nice, France, 6001
    • CHU de Nice
  • Paris cedex 8, France, 75877
    • Hôpital Bichat - Claude Bernard
  • Toulouse, France, 31400
    • Hôpital Rangueil, Service Cancérologie
  • Valenciennes, France, 59300
    • Clinique Vauban
• Germany
  • Aachen, Germany, 52074
    • University Hospital Aachen
  • Bad Krozingen, Germany, 79189
    • Universitäts-Herzzentrum Freiburg • Bad Krozingen
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Klinik
  • Berlin, Germany, 10249
    • Vivantes Klinikum im Friedrichshaim
  • Berlin, Germany, 12203
    • Charité Benjamin Franklin
  • Berlin, Germany, 13353
    • Charité, Campus Virchow-Klinikum - Medizinische Klinik mit Schwerpunkt Kardiologie
  • Bielefeld, Germany, 33604
    • Staedtische Kliniken Bielefeld
  • Bonn, Germany, 53115
    • GFO Kliniken Bonn - St.-Marien-Hospital
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn - Medizinische Klinik II - Innere Medizin (Kardiologie, Angiologie und Pneumologie)
  • Coburg, Germany, 96450
    • Klinikum Coburg Med. Klinik Kardiologie, Angiologie, Pneumologie
  • Dortmund, Germany, 44137
    • St. Johannes- Hospital
  • Düsseldorf, Germany, 40225
    • Heinrich-Heine-Universität Düsseldorf - Universitätsklinikum Düsseldorf (UKD) Klinik für Kardiologie, Pneumologie und Angiologie
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg Klinik für Kardiologie und Angiologie I
  • Hamburg, Germany, 20246
    • Universitäres Herzzentrum Hamburg GmbH (UHZ)
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg Klinik für Kardiologie, Angiologie und Pneumologie (Innere Medizin III)
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin
  • Jena, Germany, 7747
    • Universitätsklinikum Jena Klinik für Innere Medizin I, Kardiologie, Angiologie, Pneumologie, Internistische Intensivmedizin
  • Leipzig, Germany, 4289
    • Herzzentrum Leipzig - Universitätsklinik Klinik für Innere Medizin/Kardiologie
  • Ludwigshafen, Germany, 67063
    • Klinikum Ludwigshafen
  • Lüneburg, Germany, 21339
    • Stadtisches Klinikum Luneburg
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH
  • München, Germany, 81379
    • Klinik Dr. Müller GmbH & Co. KG, Peter Osypka Herzzentrum
  • Münster, Germany, 48149
    • Universitätsklinikum Münster - Department für Kardiologie und Angiologie
  • Paderborn, Germany, 33098
    • St. Vincenz-Krankenhaus Paderborn - Medizinische Klinik II
  • Rostock, Germany, 18057
    • Universitatsmedizin Rostock
  • Tübingen, Germany, 72076
    • Universitäts Klinikum Tübingen
  • Ulm, Germany, 89077
    • Herzklinik Ulm
  • Ulm, Germany, 89081
    • Universitätsklinik Ulm - Zentrum für Innere Medizin - Klinik für Innere Medizin II
  • Villingen-Schwenningen, Germany, 78052
    • Schwarzwald-Baar Klinikum - Kliniken Villingen-Schwenningen - Innere Medizin III: Kardiologie und Intensivmedizin
  • Wiesbaden, Germany, 65189
    • St. Josefs-Hospital - Medizinische Klinik I, Kardiologie
  • Wuppertal, Germany, 42117
    • HELIOS Klinikum Wuppertal - Herzzentrum
• Hungary
  • Balatonfüred, Hungary, 8230
    • Állami Szívkorhaz
  • Budapest, Hungary, 1096
    • Gottsegen György Országos Kardiológiai Intézet
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Kórház és Rendelőintézet
  • Budapest, Hungary, 1134
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary, 1023
    • Budai Irgalmasrendi Kht.
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Gyula, Hungary, 5700
    • Békés Megyei Központi Kórház
  • Győr, Hungary, 9023
    • Petz Aladar Megyei Oktato Korhaz
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem
  • Szeged, Hungary, 6725
    • Szegedi Tudomanyegyetem
  • Székesfehérvár, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
• Italy
  • Arezzo, Italy, 52100
    • Ospedale San Donato- ASL 8 Arezzo
  • Bari, Italy, 70124
    • Policlinico di Bari
  • Bologna, Italy, 40133
    • Ospedale Maggiore C.A. Pizzardi -OR - Laboratorio di Cardiologia Interventistica
  • Catanzaro, Italy, 88100
    • AOU Materdomini, Magna Graecia University
  • Chieti, Italy, 66100
    • ASL2 Chieti - SS Maria Annunziata
  • Cuneo, Italy, 12100
    • A.S.O.S. Croce e Carle Cuneo
  • Ferrara, Italy, 44124
    • AOU Sant'Anna
  • Firenze, Italy, 50134
    • Ospedale Careggi
  • Foggia, Italy, 71122
    • Ospedali riuniti di Foggia
  • Lecco, Italy, 23900
    • Ospedale Alessandro Manzoni-Azienda Ospedaliera di Lecco
  • Milano, Italy, 20157
    • Asst Fatebenefratelli-Sacco
  • Modena, Italy, 41124
    • AOU Policlinico di Modena
  • Napoli, Italy, 80131
    • University Hospital Federico II
  • Padova, Italy, 35128
    • Padova University Hospital
  • Parma, Italy, 43126
    • Azienda Ospedaliero-Universitaria di Parma
  • Rimini, Italy, 47923
    • Ospedale Degli Infermi
  • Rivoli, Italy, 10098
    • Ospedale degli Infermi di Rivoli
  • Roma, Italy, 00168
    • Policlinico Agostino Gemelli
  • Rome, Italy, 00152
    • S.Camillo Forlanini - Ospedale S.Camillo Reparto di Emodinamica
  • Seriate, Italy, 24068
    • Bolognini Hospital Seriate
  • Terni, Italy, 05100
    • "Santa Maria" University Hospital - Azienda Ospedaliera Santa Maria Di Terni
  • Verona, Italy, 37126
    • U.O. Cardiologia Ospedale Borgo Trento
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 42472
    • Daegu Catholic University Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 10380
    • Inje univ. ilsan paik hospital
  • Gyeonggi-do, Korea, Republic of, 16247
    • The Catholic University of Korea ST.VINCENT'S Hospital
  • Gyeonggi-do, Korea, Republic of, 431796
    • Hallym University Sacred Heart Hospital
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Jeonju, Korea, Republic of, 561-712
    • Chonbuk National University Hospital
  • Seongnam, Korea, Republic of, 136-200
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 136705
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 07061
    • Boramae Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Centre
  • Seoul, Korea, Republic of, 06591
    • SEOUL St.Maria
• Lithuania
  • Kaunas, Lithuania, 50009
    • Lithuanian university of Health Sciences Hospital
  • Klaipėda, Lithuania, 92288
    • Klaipeda Seamen's Hospital
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital "Santariskiu Clinic"
  • Šiauliai, Lithuania, 76231
    • Republican Siauliai Hospital
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • St Antonius hospital
  • Nijmegen, Netherlands, 6525 GA
    • Radboud University Medical Center
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstad Hospital
  • The Hague, Netherlands, 2512 VA
    • MC Haaglanden
• Poland
  • Bielsko-Biala, Poland, 43-316
    • II Oddział Kardiologiczny, Polsko-Amerykanskie Kliniki Serca
  • Chrzanów, Poland, 32-500
    • MCSN AHoP
  • Dąbrowa Górnicza, Poland, 41-300
    • III Oddział Kardiologii Inwazyjnej, Angiologii i Elektrokardiologii Polsko-Amerykanskie Kliniki Serca
  • Kraków, Poland, 31-302
    • Krakowski Szpital Specjalistyczny im. Jana Pawła II, Oddział Kliniczny Kardiologii Interwencyjnej z Pododdziałem Intenyswengo Nadzoru Kardiologicznego
  • Kędzierzyn-Koźle, Poland, 47-200
    • AHP IV DEP K-Kozle
  • Nysa, Poland, 48-300
    • Nyskie Centrum Sercowo-Naczyniowe, Polsko-Amerykanskie Kliniki Serca
  • Skierniewice, Poland, 96-100
    • Clin-Medica OMC sp. z o.o. s.k.
  • Tychy, Poland, 43-100
    • X Oddział Kardiologii Inwazyjnej, Elektrofizjologii i Elektrostymulacji Polsko-Amerykanskie Kliniki Serca
  • Warsaw, Poland, 04-628
    • Instytut Kardiologii im. Prymasa Tysiąclecia Stefana Kardynała Wyszyńskiego; Klinika Kardiologii i Angiologii Interwencyjnej
  • Warszawa, Poland, 04-628
    • Instytut Kardiologii im. Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego, Klinika Choroby Wieńcowej i Strukturalnych Chorób Serca
  • Łódź, Poland, 91-302
    • Nzoz Salus
• Portugal
  • Almada, Portugal, 2805-267
    • Hospital Garcia de Orta, EPE
  • Carnaxide, Portugal, 2790-134
    • Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitário de Coimbra, EPE
  • Coimbra, Portugal, 3041 801
    • Centro Hospitalar e Universitário de Coimbra, EPE - Hospital dos Covões
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
  • Lisboa, Portugal, 1169-024
    • Centro Hospitalar de Lisboa Central, EPE - Hospital Santa Marta
• Romania
  • Baia Mare, Romania, 430031
    • Emergency County Hospital Baia Mare
  • Bucharest, Romania, 022328
    • "Prof. C.C. Iliescu" Emergency Institute for Cardiovascular Diseases
  • Bucharest, Romania, 050098
    • University Hospital of Bucharest
  • Bucharest, Romania, 42122
    • Saint John Emergency Hospital
  • Oradea, Romania, 410169
    • Oradea Emergency County Clinical Hospital
  • Timişoara, Romania, 300310
    • Institutul de Boli Cardiovasculare Timisoara
  • Târgu-Mureş, Romania, 540136
    • Emergency Institute of Cardiovascular Diseases and Transplantation
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center -Zvezdara
  • Belgrade, Serbia, 11000
    • Institute of CV Diseases Clinical Center of Serbia
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Sremska Kamenica, Serbia, 21204
    • Institute of Cardiovascular Diseases of Vojvodina
• Spain
  • Alicante, Spain, 3010
    • General University Hospital of Alicante
  • Badalona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol
  • Granada, Spain, 18014
    • Complejo Hospitalario Universitario de Granada
  • L'Hospitalet de Llobregat, Spain, 8907
    • Bellvitge University Hospital
  • León, Spain, 24071
    • Complejo Asistencial Universitario de León
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain, 28040
    • Clinica Universitaria San Carlos
  • Madrid, Spain, 28046
    • Hospital La Paz, Madrid
  • Madrid, Spain, 280471
    • Hospital Universitario 12 de Octubre
  • Murcia, Spain, 30120
    • Hospital Universitario Virgen de la Arrixaca
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
  • Valladolid, Spain, 47005
    • Hospital Clínico Universitario de Valladolid
  • Vigo, Spain, 36312
    • Hospital Álvaro Cunqueiro
• Switzerland
  • Fribourg, Switzerland, 1700
    • HFR Freiburg - Kantonsspital Kardiologie
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
• Taiwan
  • Hsinchu, Taiwan, 30071
    • Hsinchu Mackay Memorial Hospital (HMMH)
  • Kaohsiung, Taiwan, 824
    • E-DA Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital (FEMH)
  • Taichung, Taiwan, 404
    • China Medical University Hospital (CMUH)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan, Taiwan, 704
    • Chi-Mei Medical Center (CMMC)
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 112
    • Cheng Hsin General Hospital
  • Taoyuan, Taiwan, 333
    • Chang-Gung Memorial Hospital
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Regional Cardiological Center
  • Chernihiv, Ukraine, 14034
    • Chernihiv City Hospital #2
  • Chernivtsi, Ukraine, 58013
    • Chernivtsi Regional Clinical Cardiology Dispensary
  • Dnipro, Ukraine, 49060
    • Communal Institution Dnepropetrovsk Regional Diagnostic Center
  • Dnipropetrovsk, Ukraine, 49006
    • CI "Dnipropetrovsk Joint Emergency Hospital"
  • Ivano-Frankivs'k, Ukraine, 76018
    • Ivano-Frankivsk Central City Clinical Hospital
  • Kharkiv, Ukraine, 61039
    • L.T. Malaya Therapy National Institute of the National Academy of medical science of Ukraine
  • Kharkiv, Ukraine, 61058
    • Communal Health Care Institution "Regional Clinical Hospital - Center of Emergency Medical Care and Disaster Medicine"
  • Kharkiv, Ukraine, 61178
    • Kharkiv City Clinical Hospital #8
  • Kharkov, Ukraine, 61000
    • Kharkiv Railway Clinical Hospital N1 of Brance "Health Center" of the Public joint stock company "Ukrainian Railway"
  • Khmel'nyts'kyy, Ukraine, 29000
    • Khmelnytskyy regional hospital
  • Kyiv, Ukraine, 02660
    • Insititute of Heart of MoH Ukraine
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Hospital#5
  • Kyiv, Ukraine, 03151
    • State Institution 'National Scientific Central Institute of Cardiology named after MD Strazhesko'
  • Kyiv, Ukraine, 04112
    • Kyiv City Clinical Hospital 4
  • Kyiv, Ukraine, 1601
    • Oleksandrivska Kiyv City Clinical Hospital
  • Kyiv, Ukraine, 4107
    • Communal Institution of Kyiv Regional Rada
  • L'viv, Ukraine, 79015
    • Lviv Regional State Clinical Treatment and Diagnostic Cardiology Center
  • Luts'k, Ukraine, 43024
    • Lutsk City Hospital
  • Nikolayev, Ukraine, 54003
    • Nikolaev Regional Clinical Hospital
  • Odessa, Ukraine, 65025
    • Odessa Regional Hospital, Cardiosurgery Center
  • Rivne, Ukraine, 33007
    • Communal Institution Rivne Regional Clinical Hospital
  • Sumy, Ukraine, 40031
    • Communal Institution of Sumy Regional Rada
  • Uzhhorod, Ukraine, 88018
    • Transcarpathian Regional Clinical Cardiology Clinic
  • Vinnytsya, Ukraine, 21000
    • Communal Institution "Vinnytsia Regional Diagnostic Center of cardiovascular disease"
  • Vinnytsya, Ukraine, 21000
    • Vinnytsya Regional Clinical Hospital n.a. Pyrogov
  • Zaporizhzhia, Ukraine, 69000
    • Zaporizhzhia Regional cardiology dispensary
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Clydebank, United Kingdom, G81 4DY
    • Golden Jubilee Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Londonderry, United Kingdom, BT47 6SB
    • Altnagelvin Area Hospital
  • Portadown, United Kingdom, BT63 5QQ
    • Southern Health and Social Care Trust
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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,

  1. 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.

  2. 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:

  1. cardiogenic shock or acute decompensated heart failure, with the requirement for vasopressor agents or inotropic support or mechanical support to support circulation
  2. 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:

  1. Platelet count < 50 x10^9/L
  2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Edoxaban 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.	Drug: Edoxaban; Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects; Other Names: Savaysa; Drug: Clopidogrel; Clopidogrel 75 mg once-daily; Other Names: Plavix; Drug: Prasugrel; prasugrel 5mg or 10 mg once-daily; Other Names: Effient; Drug: Ticagrelor; ticagrelor 90 mg twice-daily
ACTIVE_COMPARATOR: Vitamin K Antagonist Regimen; 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.	Drug: Clopidogrel; Clopidogrel 75 mg once-daily; Other Names: Plavix; Drug: Prasugrel; prasugrel 5mg or 10 mg once-daily; Other Names: Effient; Drug: Ticagrelor; ticagrelor 90 mg twice-daily; Drug: Vitamin K antagonist; VKA once-daily dosing for target international normalized ratio between 2.0 and 3.0, inclusive

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adjudicated Major or Clinically Relevant Non-major Bleeding As First Event Defined by International Society on Thrombosis and Haemostasis Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	Participants' first major or clinically relevant non-major bleeding (MCRB) events were reported. International Society on Thrombosis and Hemostasis (ISTH) defined bleeding events included: MCRB, major bleeding, including fatal bleeding (intracranial and non-intracranial), symptomatic intracranial hemorrhage, symptomatic bleeding in a critical area or organ, and clinically overt and causing ≥2.0 g/dL adjusted hemoglobin loss, clinically relevant non-major (CRNM) bleeding, minor bleedings, any bleeding (defined as the composite of major, CRNM, and minor bleeding), life-threatening bleeding, provoked (spontaneous, instrumental/traumatic, unknown) bleeding, and spontaneous bleeding.	Day 1 to 12 months postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adjudicated Major, Clinically Relevant Non-major and Minor Bleeding (All Events) Defined by International Society on Thrombosis and Haemostasis Following Edoxaban-based Regimen Compared With Vitamin K Antagonist-Based Regimen	All major, clinically relevant non-major and minor bleeding are reported for the secondary outcome. Participants may have experiences more than 1 bleeding event, all occurrences are reported. Participants with International Society on Thrombosis and Hemostasis (ISTH) defined bleeding events included: major or clinically relevant non-major bleeding (MCRB), major bleeding, including fatal bleeding (intracranial and non-intracranial), symptomatic intracranial hemorrhage, symptomatic bleeding in a critical area or organ, and clinically overt and causing ≥2.0 g/dL adjusted hemoglobin loss, clinically relevant non-major (CRNM) bleeding, minor bleedings, any bleeding (defined as the composite of major, CRNM, and minor bleeding), life-threatening bleeding, provoked (spontaneous, instrumental/traumatic, unknown) bleeding, and spontaneous bleeding.	Day 1 to 12 months postdose
Number of Participants With Adjudicated Major, Minor, and Minimal Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Definition Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	Thrombolysis in Myocardial Infarction (TIMI) defined bleeding events included: Major bleeding (including fatal bleeding and non-fatal bleeding [fulfilling the TIMI major bleeding definition], major or minor bleeding, minor bleeding, minimal bleeding, and any bleeding (defined as composite of major, minor, and minimal bleeding)	Day 1 to 12 months postdose
Number of Participants With Bleeding Academic Research Consortium (BARC) Type 1, 2, 3, and 5 Bleeding According to the BARC Definitions Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	Bleeding Academic Research Consortium (BARC) bleeding events included: Bleeding (defined by BARC type 3 or 5), bleeding (defined by BARC type 2, 3, or 5), and any bleeding (defined as the composite of BARC type 1, 2, 3, or 5), where increases in BARC type indicate worse outcome. Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy by the patient without consultation; Type 2: any overt, actionable sign of hemorrhage that does not fit the criteria for type 3, 4, or 5 but does meet at least one of the following criteria: (1) requiring nonsurgical, medical intervention, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation; Type 3: Overt bleeding plus hemoglobin drop of 3 to ≤5 g/dL (3a), ≥5 g/dl (3b), and intracranial hemorrhage (3c) Type 5: Fatal bleeding	Day 1 to 12 months postdose
Number of Participants With Main Efficacy Endpoints For the Overall Study Period Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	The main efficacy endpoints were defined as the composite of cardiovascular death (ARC), stroke (protocol defined), systemic embolic event (SEE), myocardial infarction (MI), or definite stent thrombosis.	Day 1 to 12 months postdose
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	Treatment-emergent adverse events (TEAEs) in >1.0% of participants were defined as events which started on or after first dose of the assigned study drug (edoxaban and VKA) or started prior to but then worsened after the first dose of the assigned study drug.	Day 1 to 30 days after the last dose
Number of Participants With Study Drug-related Treatment-emergent Adverse Events (TEAEs) Experienced by 2 or More Participants Following Edoxaban-based Regimen Compared With Vitamin K Antagonist (VKA)-Based Regimen	Study drug-related treatment-emergent adverse events (TEAEs) (experienced by 2 or more participants) were defined as events which started on or after first dose of the assigned study drug (edoxaban and VKA) or started prior to but then worsened after the first dose of the assigned study drug and were found to be related to treatment by the Investigator.	Day 1 to 30 days after the last dose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
• Investigators: Study Chair: Pascal Vranckx, MD, Hartcentrum Hasselt; Study Chair: Andreas Gotte, Prof., MD, Medizinische Klinik II

Publications and helpful links

General Publications

• Goette A, Eckardt L, Valgimigli M, Lewalter T, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Tijssen JG, Vranckx P. Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis. Clin Res Cardiol. 2021 Jun;110(6):831-840. doi: 10.1007/s00392-020-01760-4. Epub 2020 Oct 24.
• Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, Batushkin V, Campo G, Lysak Z, Vakaliuk I, Milewski K, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Goette A. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet. 2019 Oct 12;394(10206):1335-1343. doi: 10.1016/S0140-6736(19)31872-0. Epub 2019 Sep 3.
• Vranckx P, Lewalter T, Valgimigli M, Tijssen JG, Reimitz PE, Eckardt L, Lanz HJ, Zierhut W, Smolnik R, Goette A. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial. Am Heart J. 2018 Feb;196:105-112. doi: 10.1016/j.ahj.2017.10.009. Epub 2017 Oct 23.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2017
• Primary Completion (ACTUAL): June 6, 2019
• Study Completion (ACTUAL): June 6, 2019

Study Registration Dates

• First Submitted: August 10, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (ESTIMATE): August 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2020
• Last Update Submitted That Met QC Criteria: April 24, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: vitamin K antagonist; percutaneous intervention
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Micronutrients; Vitamins; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Ticagrelor; Clopidogrel; Vitamin K; Edoxaban; Prasugrel Hydrochloride
• Other Study ID Numbers: DSE-EDO-01-15-EU; 2016-002683-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing 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 and/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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No