Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation (ENVISAGE-TAVI AF)

Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation (TAVI) - in Atrial Fibrillation

When the upper chambers of a person's heart receive or generate irregular electrical signals, it causes abnormal rhythm in the heartbeat. This is called atrial fibrillation.

Atrial fibrillation goes along with blood clots that may cause mainly strokes and less often other diseases, such as a heart attack. Some patients with atrial fibrillation have other heart disease, such as heart valves that may need to be replaced using catheters.

Often doctors give patients drugs that reduce those blood clots. These are either vitamin K antagonist (VKA) or direct anticoagulants, such as edoxaban. In these patients, it is unclear which of the drugs is better for reducing stroke without increasing severe bleedings.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Edoxaban-based Regimen; Drug: VKA-based Regimen

Detailed Description

Use of Edoxaban in patients with atrial fibrillation (AF) and indication to chronic oral anticoagulation (OAC) after transcatheter aortic valve implantation (TAVI)

Objective:

• To assess the effect of Edoxaban versus vitamin K antagonist (VKA) on net adverse clinical events (NACE), i.e., the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SEE), valve thrombosis, and major bleeding (International Society on Thrombosis and Haemostasis [ISTH] definition).
• To assess the effect of Edoxaban versus VKA on major bleeding (ISTH definition).

• Study Type: Interventional
• Enrollment (Actual): 1426
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz
  • Grieskirchen, Austria, 4710
    • Clinic Wels-Grieskirchen GmbH
  • Innsbruck, Austria, 6020
    • Universitaetsklinik fuer Innere Medizin III
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörthersee
  • Vienna, Austria, 1130
    • Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel
  • Vienna, Austria, 1090
    • Universitätsklinik für Innere Medizin II
  • Wien, Austria, 1060
    • Wilhelminenspital
• Belgium
  • Aalst, Belgium, 9300
    • ASZ Aalst - Aalst campus
  • Antwerpen, Belgium, 2060
    • ZNA - Stuivenberg Ziekenhuis Netwerk Antwerpen
  • Brussels, Belgium, B-1070
    • Hospital Erasme
  • Edegem, Belgium, 2650
    • UZA - Universtiair Ziekenhuis Antwerpen
  • Genk, Belgium, 3600
    • ZOL Genk, Campus Sint-Jan
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis- Campus Virga Jessa
  • Liège, Belgium, B-4000
    • CHU de Liège
  • Roeselare, Belgium, 8800
    • AZ Delta Roeselare
• Canada
  • Hamilton, Canada, L8L 2X2
    • Hamilton General Hospital
  • Québec, Canada, G1V 4G5
    • Universite Laval
  • Saint John, Canada, E2L4L2
    • Horizon Health Network
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R7
      • University of Alberta Hospital
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada, L3Y 3S9
      • Newmarket Cardiac Surgery Research Incorporated
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• France
  • Angers, France
    • CHU d'Angers
  • Bordeaux, France, 33074
    • Clinique Saint Augustin
  • Créteil, France, 94000
    • Hopital Henri Mondor
  • Lille, France, 59000
    • Institut Coeur Poumon - CHRU de Lille
  • Montpellier, France, 34295
    • CHU Arnaud de Villeneuve
  • Montpellier, France, 34960
    • Clinique du Millenaire Service de Cardiologie Interventionelle
  • Paris, France, 75877
    • Hôpital Bichat
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Pessac, France, 33604
    • CHU de Bordeaux Hôpital du Haut Lévèque
  • Rouen, France, 76000
    • CHU de Rouen
  • Rouen, France, 76000
    • Clinique Saint-Hilaire
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil
  • Toulouse, France, 31300
    • Clinique Pasteur / GCVI
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-klinik
  • Bad Neustadt An Der Saale, Germany, 97616
    • Herz und Gefaess Klinik
  • Bad Segeberg, Germany, 23795
    • Segeberger Kliniken
  • Berlin, Germany, 12200
    • Charite Universitatsmedizin Berlin
  • Berlin, Germany, 16321
    • Immanuel Klinikum Bernau Herzzentrum Brandenburg
  • Bremen, Germany, 28277
    • Gesundheit Nord gGmbH
  • Dortmund, Germany, 44137
    • Klinikum der Stadt Ludwigshafen
  • Dortmund, Germany, 44137
    • St. Johannes - Hospital
  • Dresden, Germany, 01307
    • Heart Center Dresden, University Clinic Technical University Dresden
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Essen, Germany, 45138
    • Elisabeth Krankenhaus Essen Klinik fur Kardiologie und Angiologie
  • Fulda, Germany, 36043
    • Klinikum Fulda gAG
  • Halle, Germany, 06120
    • Universitätsklinikum Halle (Saale)
  • Hamburg, Germany, 20099
    • Asklepios St. Georg Abteilung fuer Kardiologie
  • Heidelberg, Germany, 69120
    • Heidelberg University Hospital
  • Kiel, Germany, 24105
    • Universitaetsklinik Schleswig-Holstein Campus Kiel
  • Lahr, Germany, 77933
    • MediClin Herzzentrum Lahr/Baden
  • Leipzig, Germany, 4289
    • Herzzentrum Leipzig
  • Mainz, Germany, 55131
    • Universitatsmedizin Mainz, Zentrum fur Kardiologie
  • Muenchen, Germany, 81675
    • Klinikum Rechts Der Isar Der Technischen Universität München
  • München, Germany, 80636
    • Deutsches Herzzentrum München
  • München, Germany, 81379
    • Universitatsklinikum Essen, Klinik fur Kardiologie
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg AöR
  • Regensburg, Germany, 93042
    • Uniklinikum Regensburg, Med II
  • Trier, Germany, 54292
    • Krankenhaus der Barmherzigen
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen Medizinische Klinik, Abteilung III
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • Wuppertal, Germany, 42117
    • Helios Herzzentrum Wuppertal
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Italy
  • Ancona, Italy, 60030
    • Ospedali Riuniti Torrette di Ancona
  • Bologna, Italy, 40138
    • Policlinico Sant'Orsola-Malpighi
  • Brescia, Italy, 25123
    • ASST Spedali Civili di Brescia-UO Cardiologia
  • Catania, Italy, 95123
    • AOU Policlinico Vittorio Emanuele
  • Catanzaro, Italy, 88100
    • Magna Graecia University
  • Cuneo, Italy, 12100
    • Ospedale S. Croce e Carle
  • Lecce, Italy, 73100
    • Città di Lecce Hospital
  • Lecco, Italy, 23900
    • Azienda Socio Sanitaria Territoriale di Lecco
  • Legnano, Italy, 20025
    • ASST Ovest Milanese - Presidio Ospedallero di Legnana
  • Massa, Italy, 54100
    • Fondazione Toscana Gabriele Monasterio
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20138
    • Centro Cardiologico Monzino IRCCS
  • Napoli, Italy, 80122
    • Clinica Mediterranea
  • Napoli, Italy, 80131
    • A.A Dei Colli Monaldi UOC Cardiologia Interventistica
  • Padova, Italy, 35121
    • Azienda Ospedaliera di Padova
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Pedara, Italy, 95030
    • Centro Cuore Morgagni
  • Pisa, Italy, 56124
    • Azienda Ospedaliero-Universitaria Pisana
  • Reggio Emilia, Italy, 42123
    • IRCCS-ASMN Reggio Emilia
  • Rome, Italy, 00152
    • AO San Camillo Forlanini
  • Rome, Italy, 00161
    • Azienda Ospedaliero-Universitaria Policlinico Umberto I
  • Rome, Italy, 00187
    • AOU Careggi, Interventistica Cardiologica Strutturale
  • Rome, Italy, 00189
    • Ospedale Sant'Andrea - U.O.S. Emodinamica Cardiologia Interventistica
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
  • Salerno, Italy, 84133
    • AOU S.Giovanni Di Dio e Ruggi D'Aragona
  • San Donato Milanese, Italy
    • IRCCS Policlinico San Donato
  • Siena, Italy, 53100
    • UOC Emodinamica III
  • Verona, Italy, 37126
    • Azienda Ospedaliera Integrata di Verona
• Japan
  • Aichi, Japan, 441-8530
    • Toyohashi Heart Center
  • Chiba, Japan, 270-2232
    • New Tokyo Hospital
  • Kanagawa, Japan, 247-0072
    • Shonan Kamakura General Hospital
  • Toyama, Japan, 930-0194
    • Toyama University Hospital
  • Aichi
    • Toyohashi, Aichi, Japan, 441-8530
      • Nagoya Heart Center
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
  • Gifu
    • Ōgaki, Gifu, Japan, 503-0864
      • Ogaki Municipal Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 065-0033
      • Sapporo Higashi Tokushukai Hospital
  • Ibaraki
    • Amakubo, Ibaraki, Japan, 305-8558
      • Tsukuba Medical Center Hospital
  • Itabashi
    • Tokyo, Itabashi, Japan, 173-0003
      • Teikyo University Hospital
  • Iwate Prefecture
    • Morioka, Iwate Prefecture, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
    • Kawasaki, Kanagawa, Japan, 216-0015
      • St. Marianna University School of Medicine Hospital
    • Yokohama, Kanagawa, Japan, 230-8765
      • Saiseikai Yokohamashi Tobu Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Osaka
    • Abeno Ward, Osaka, Japan, 545-8586
      • Osaka City University Hospital
    • Kishiwada, Osaka, Japan, 596-0042
      • Kishiwada Tokushukai Hospital
  • Tokyo
    • Shinjuku City, Tokyo, Japan, 160-0016
      • Keio University Hospital
• Korea, Republic of
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of
      • Seoul National University Hospital
  • Seocho-gu
    • Seoul, Seocho-gu, Korea, Republic of, 06591
      • Seoul st. mary's hospital
  • Seodaemun-gu
    • Seoul, Seodaemun-gu, Korea, Republic of
      • Yonsei University Severance Hospital
  • Seongbuk-gu
    • Seoul, Seongbuk-gu, Korea, Republic of, 02841
      • Korean University Anam Hospital
  • Songpa-gu
    • Seoul, Songpa-gu, Korea, Republic of
      • Asan Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Den Haag, Netherlands, 2504 LN
    • HagaZiekenhuis
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leeuwarden, Netherlands, 8934 AD
    • Medisch Centrum Leeuwarden
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus Medical Center
• Poland
  • Białystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Gdańsk, Poland, 80-952
    • University Clinical Centre in Gdansk
  • Poznań, Poland, 61-848
    • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego Im. Karola Marcinkowskiego w Poznaniu
• Spain
  • A Coruña, Spain, 15706
    • Complexo Hospitalario Universitario De Santiago De Compostela
  • Alicante, Spain, 03540
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebrón
  • Barcelona, Spain, 08036
    • Hospital Clínico y Provincial de Barcelona
  • Grenada, Spain, 18014
    • Complejo Asistencial de Granada
  • La Coruña, Spain, 15006
    • Complexo Hospitalario Universitario de A Coruña
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28003
    • Hospital La Luz QuironSalud
  • Murcia, Spain, 31020
    • Hospital Virgen de la Arrixaca
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Santander, Spain, 39008
    • Valdecilla Hospital
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
  • Valladolid, Spain, 47003
    • Hospital Clínico Universitario de Valladolid
  • Vigo, Spain, 36312
    • Hospital Universitario Alvaro Cunqueiro
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Hospital Universitario Virgen Macarena
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Gipuzkoa
    • Donostia, Gipuzkoa, Spain, 20014
      • Hospital Universitario Donostia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitatsspital Basel
  • Bern, Switzerland, 3010
    • Bern University Hospital
  • Geneve, Switzerland, 1205
    • Hopitaux Universitaires de Geneve
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
• United Kingdom
  • Leicester, United Kingdom, LE3 9QP
    • University Hospitals Of Leicester Nhs Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • England
    • Brighton, England, United Kingdom, BN2 5BE
      • BSUH, Cardiac Research Unit
    • Cambridge, England, United Kingdom, CB23 3RE
      • Papworth Hospital NHS Foundation Trust
    • Edinburgh, England, United Kingdom, EH16 4SA
      • Royal Edinburgh Infirmary
    • London, England, United Kingdom, SE1 7EH
      • Guys St Thomas Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Trent Cardiac Centre
    • Oxford, England, United Kingdom, OX3 9DU
      • Oxford University Hospitals, John Radcliffe Hospital
    • Sheffield, England, United Kingdom, S5 7AU
      • Northern General Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • University Hospital of Wales, Heath Park
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Sarver Heart Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Site Management Services
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90048
      • Cedar-Sinai Heart Institute
    • Los Angeles, California, United States, 90095
      • UCLA Cardiovascular Center
    • San Francisco, California, United States, 94143
      • University of California - San Francisco
    • Santa Barbara, California, United States, 93105-4365
      • Santa Barbara Cottage Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20037
      • Medical Facility Associates
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Cardiology Associate Research
    • Doral, Florida, United States, 33166
      • International Research Partners, LLC.
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare Systems
    • Jacksonville, Florida, United States, 32209
      • Uf Health Jacksonville
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Research
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 77030
      • St. Vincent Heart Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Maine
    • Scarborough, Maine, United States, 04074-7133
      • Maine Medical Center
  • Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Health
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Clinical Research Institute
    • Midland, Michigan, United States, 48670
      • MidMichigan Medical Center Midland
    • Ypsilanti, Michigan, United States, 48197
      • Michigan Heart, St. Joseph Mercy Health System
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
    • Saint Paul, Minnesota, United States, 55104
      • HealthEast Medical Research Institute
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Jackson Heart Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63119
      • Clinical Investigators LLC
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute
  • New York
    • Brooklyn, New York, United States, 11215
      • NY Presbyterian - Brooklyn Methodist Hospital
    • East Hills, New York, United States, 11548
      • St. Francis Hospital
    • East Syracuse, New York, United States, 13057
      • St. Joseph's Physicians
    • Geneva, New York, United States, 14456
      • Rochester General Hospital
    • Manhasset, New York, United States, 11030
      • Northshore Community Hospital
    • New York, New York, United States, 10029
      • Mt. Sinai Hospital
    • Stony Brook, New York, United States, 11794-8167
      • Stony Brook University Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health
    • Greenville, North Carolina, United States, 27834
      • East Carolina Heart Institute
  • Ohio
    • Toledo, Ohio, United States, 43615
      • ProMedica Toledo Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital Research Foundation
  • Oregon
    • Medford, Oregon, United States, 97504
      • Southern Oregon Cardiology
    • Portland, Oregon, United States, 97225
      • Providence Heart and Vascular Institute
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Health Cardiothoracic Surgery
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health, Milton S. Hershey Medical Center
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley Medical Center
    • Wormleysburg, Pennsylvania, United States, 17043
      • Pinnacle Health
    • York, Pennsylvania, United States, 17403
      • WellSpan York Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI - Centennial Medical Center
  • Texas
    • Austin, Texas, United States, 78745
      • Seton Heart Institute
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center Houston
    • Plano, Texas, United States, 75024
      • Legacy Heart Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Spokane, Washington, United States, 99208
      • Providence Sacred Heart Medical Research Center
  • West Virginia
    • Charleston, West Virginia, United States, 25404
      • CAMC Memorial Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

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:

• Meets protocol-specified criteria for qualification and contraception
• Is willing and able to comply with any restrictions related food, drink and medications
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
  3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edoxaban-based Regimen; Edoxaban-based regimen 60 mg and 30 mg film coated tablet for once-daily oral use, and 15 mg film coated tablet in case of transitioning at the end of treatment. Dosing must follow the locally approved label.	Drug: Edoxaban-based Regimen; 15 mg, 30 mg and 60 mg film coated tablet for oral use (with anti-platelet therapy pre-declared at randomization if prescribed); Other Names: Lixiana; Savaysa
Active Comparator: VKA-based Regimen; VKA-based regimen oral VKA tablets as selected and provided by the site and used in accordance with the local label. The Investigator will monitor the patient and adjust the VKA dose to maintain the dose within target.	Drug: VKA-based Regimen; Dosed at International Normalized Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in the country location (with anti-platelet therapy pre-declared at randomization if prescribed).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on ISTH Criteria in Participants Taking Edoxaban vs VKA	The composite endpoint net adverse clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding per definition of the International Society on Thrombosis and Haemostasis (ISTH].	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Major Bleeding (Adjudicated Data) Based on ISTH Criteria in Participants Taking Edoxaban vs VKA	ISTH Bleeding Criteria for Major Bleeding are defined as clinically overt bleeding that is associated with: a fall in hemoglobin of 2 g/dL (1.24 mmol/L) or more, or a transfusion of 2 or more units of whole blood or packed red blood cells, or symptomatic bleeding into a critical site or organ such as intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intra-articular, or intramuscular with compartment syndrome, or a fatal outcome.	Baseline through study completion, up to 36 months post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on TIMI Criteria in Participants Taking Edoxaban vs VKA	The composite endpoint of net adverse event clinical events (NACE) included all-cause death, myocardial infarction (MI), ischemic stroke, systemic embolic events (SEE), valve thrombosis, and major bleeding based on Thrombolysis in Myocardial Infarction (TIMI) criteria. Bleeding by TIMI criteria was defined as the following: (1) Major, any intracranial hemorrhage or any clinically overt bleeding, (including bleeding evident in imaging studies) associated with a fall of hemoglobin (Hb) of ≥ 5g/dL or fatal bleeding and (2) Minor, any clinically overt bleeding associated with a fall in Hb ≥ 3g/dL but < 5 g/dL.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on BARC Type 3 or 5 Criteria in Participants Taking Edoxaban vs VKA	The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Bleeding Academic Research Consortium (BARC) Type 3 or 5 criteria. Major bleeding by BARC criteria was defined as Type 3: clinical, laboratory, and/or imaging evidence of bleeding with provider responses; Type 3a: any transfusion with overt bleeding; overt bleeding plus Hb drop of 3 to < 5 g/dL; Type 3b: overt bleeding plus Hb drop ≥ 5 g/dL; cardiac tamponade; bleeding requiring surgical intervention; bleeding requiring intravenous vasoactive drugs; Type 3c: intracranial hemorrhage; subcategories confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 5: fatal bleeding; Type 5a: probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious; Type 5b: definite fatal bleeding; overt bleeding or autopsy or imaging confirmation	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on GUSTO Criteria in Participants Taking Edoxaban vs VKA	The composite endpoint of net adverse event clinical events (NACE) included all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding based on Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO). GUSTO criteria was defined as the following: severe or life threatening: intracerebral hemorrhage or resulting in substantial hemodynamic compromise requiring treatment and moderate: requiring blood transfusion but not resulting in hemodynamic compromise.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Major Adverse Cardiac Events (MACE) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Major adverse cardiac events (MACE) is defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, or repeat coronary revascularization of the target lesion.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Major Adverse Cardiac and Cerebrovascular Events (MACCE) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Major adverse cardiac and cerebrovascular events (MACCE) is defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, stroke (ischemic, hemorrhagic, or undetermined), or repeat coronary revascularization of the target lesion	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced a Composite of Adverse Events in Participants Taking Edoxaban vs VKA (Adjudicated Data)	A composite of clinical adverse events included cardiovascular death, MI ischemic stroke, SEE, valve thrombosis, and major bleeding as defined by ISTH criteria.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Stroke Events (Ischemic, Hemorrhagic, Undetermined) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Stroke events are categorized as any stroke, fatal stroke, and non-fatal stroke.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Systemic Embolic Events in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Systemic thromboembolism [non-central nervous system] is defined as abrupt vascular insufficiency of an extremity or organ associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (e.g., trauma, atherosclerosis, instrumentation).	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Myocardial Infarctions (MI) in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Peri-procedural MI was defined as new ischemic symptoms or signs and elevated cardiac biomarkers within 72 hours after index procedure, consisting of at least one sample post-procedure with a peak value exceeding 15x as the upper reference limit (URL) for troponin or 5x for CK-MB. Spontaneous MI is defined as any one of the following: Detection of rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile URL, together with the evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia; ECG changes indicative of new ischemia; New pathological Q-waves in at least two contiguous leads; Imaging evidence of a new loss of viable myocardium or new wall motion abnormality; Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied by new ST elevation or new left bundle branch block, and/or evidence of fresh thrombus; Pathological findings of an acute MI.	Baseline through study completion, up to 36 months post-dose
Number of Participants Who Experienced Valve Thrombosis in Participants Taking Edoxaban vs VKA (Adjudicated Data)	Valve thrombosis was defined as any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.	Baseline through study completion, up to 36 months post-dose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Chiltern International Inc.

Publications and helpful links

General Publications

• Van Mieghem NM, Unverdorben M, Hengstenberg C, Mollmann H, Mehran R, Lopez-Otero D, Nombela-Franco L, Moreno R, Nordbeck P, Thiele H, Lang I, Zamorano JL, Shawl F, Yamamoto M, Watanabe Y, Hayashida K, Hambrecht R, Meincke F, Vranckx P, Jin J, Boersma E, Rodes-Cabau J, Ohlmann P, Capranzano P, Kim HS, Pilgrim T, Anderson R, Baber U, Duggal A, Laeis P, Lanz H, Chen C, Valgimigli M, Veltkamp R, Saito S, Dangas GD; ENVISAGE-TAVI AF Investigators. Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR. N Engl J Med. 2021 Dec 2;385(23):2150-2160. doi: 10.1056/NEJMoa2111016. Epub 2021 Aug 28.
• Giacoppo D. Anticoagulation After Transcatheter Aortic Valve Replacement: Evolving Answers and Still Unaddressed Questions. JACC Cardiovasc Interv. 2021 Aug 9;14(15):1714-1716. doi: 10.1016/j.jcin.2021.06.004. Epub 2021 Jul 14. No abstract available. Erratum In: JACC Cardiovasc Interv. 2021 Oct 25;14(20):2311-2313.
• Van Mieghem NM, Unverdorben M, Valgimigli M, Mehran R, Boersma E, Baber U, Hengstenberg C, Shi M, Chen C, Saito S, Veltkamp R, Vranckx P, Dangas GD. Edoxaban Versus standard of care and their effects on clinical outcomes in patients having undergone Transcatheter Aortic Valve Implantation in Atrial Fibrillation-Rationale and design of the ENVISAGE-TAVI AF trial. Am Heart J. 2018 Nov;205:63-69. doi: 10.1016/j.ahj.2018.07.006. Epub 2018 Aug 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2017
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): February 28, 2021

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Anticoagulation; Transcatheter Aortic Valve Implantation -- TAVI; ENVISAGE-TAVI-AF
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban
• Other Study ID Numbers: DU176B-C-U4001; 2016-003930-26 (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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No