AzTrials
AzTrials

Atrial FibrillationPhase 3NCT02943785

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

A Phase 3 study testing Edoxaban-based Regimen and VKA-based Regimen in people with Atrial Fibrillation, run by Daiichi Sankyo at 230 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Edoxaban-based Regimen and VKA-based Regimen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,426 participants
Where
230 sitesin 14 countries
Study dates
21 Mar 2017to 28 Feb 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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:
  • the safety or well-being of the participant or study staff
  • the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
  • the analysis of results

Trial locations and contacts

230 sites in 14 countries.

230 sites in 14 countries

United States66 sites

  • New Mexico Heart Institute

    Albuquerque, New Mexico, 87102

  • Seton Heart Institute

    Austin, Texas, 78745

  • St. Luke's University Health Network

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • NY Presbyterian - Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • CAMC Memorial Hospital

    Charleston, West Virginia, 25404

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Cardiology Associate Research

    Daytona Beach, Florida, 32117

  • International Research Partners, LLC.

    Doral, Florida, 33166

  • Doylestown Health Cardiothoracic Surgery

    Doylestown, Pennsylvania, 18901

  • Essentia Health

    Duluth, Minnesota, 55805

  • St. Francis Hospital

    East Hills, New York, 11548

  • St. Joseph's Physicians

    East Syracuse, New York, 13057

  • Inova Heart and Vascular Institute

    Falls Church, Virginia, 22042

  • Rochester General Hospital

    Geneva, New York, 14456

  • Moses H. Cone Memorial Hospital Operating Corporation d/b/a Cone Health

    Greensboro, North Carolina, 27401

  • East Carolina Heart Institute

    Greenville, North Carolina, 27834

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Health, Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Memorial Healthcare Systems

    Hollywood, Florida, 33021

  • Houston Methodist Research Institute

    Houston, Texas, 77030

  • University of Texas Health Science Center Houston

    Houston, Texas, 77030

  • St. Vincent Heart Center

    Indianapolis, Indiana, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Jackson Heart Clinic

    Jackson, Mississippi, 39216

  • UF Health Jacksonville

    Jacksonville, Florida, 32209

  • Watson Clinic Center for Research

    Lakeland, Florida, 33805

  • Sparrow Clinical Research Institute

    Lansing, Michigan, 48912

  • Arkansas Site Management Services

    Little Rock, Arkansas, 72211

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Cedar-Sinai Heart Institute

    Los Angeles, California, 90048

  • UCLA Cardiovascular Center

    Los Angeles, California, 90095

  • Northshore Community Hospital

    Manhasset, New York, 11030

  • Southern Oregon Cardiology

    Medford, Oregon, 97504

  • MidMichigan Medical Center Midland

    Midland, Michigan, 48670

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • SCRI - Centennial Medical Center

    Nashville, Tennessee, 37203

  • Mt. Sinai Hospital

    New York, New York, 10029

  • Oklahoma Heart Hospital Research Foundation

    Oklahoma City, Oklahoma, 73120

  • The Valley Hospital

    Paramus, New Jersey, 07652

  • Legacy Heart Center

    Plano, Texas, 75024

  • Providence Heart and Vascular Institute

    Portland, Oregon, 97225

  • Black Hills Cardiovascular Research

    Rapid City, South Dakota, 57701

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • HealthEast Medical Research Institute

    Saint Paul, Minnesota, 55104

  • University of California - San Francisco

    San Francisco, California, 94143

  • Santa Barbara Cottage Hospital

    Santa Barbara, California, 93105-4365

  • Maine Medical Center

    Scarborough, Maine, 04074-7133

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Providence Sacred Heart Medical Research Center

    Spokane, Washington, 99208

  • Baystate Health

    Springfield, Massachusetts, 01199

  • Clinical Investigators LLC

    St Louis, Missouri, 63119

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794-8167

  • Washington Adventist Hospital

    Takoma Park, Maryland, 20912

  • Tallahassee Research Institute, Inc.

    Tallahassee, Florida, 32308

  • Promedica Toledo Hospital

    Toledo, Ohio, 43615

  • University of Arizona Sarver Heart Center

    Tucson, Arizona, 85724

  • Carle Foundation Hospital

    Urbana, Illinois, 61801

  • Medstar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Medical Facility Associates

    Washington D.C., District of Columbia, 20037

  • Geisinger Wyoming Valley Medical Center

    Wilkes-Barre, Pennsylvania, 18711

  • University of Massachusetts Memorial Medical Center

    Worcester, Massachusetts, 01655

  • Pinnacle Health

    Wormleysburg, Pennsylvania, 17043

  • WellSpan York Hospital

    York, Pennsylvania, 17403

  • Michigan Heart, St. Joseph Mercy Health System

    Ypsilanti, Michigan, 48197

Other trials in United States

Italy30 sites

  • Ospedali Riuniti Torrette Di Ancona

    Ancona, 60030

  • Policlinico Sant'Orsola-Malpighi

    Bologna, 40138

  • ASST Spedali Civili di Brescia-UO Cardiologia

    Brescia, 25123

  • AOU Policlinico Vittorio Emanuele

    Catania, 95123

  • Magna Graecia University

    Catanzaro, 88100

  • Ospedale S. Croce e Carle

    Cuneo, 12100

  • Citta di Lecce Hospital

    Lecce, 73100

  • Azienda Socio Sanitaria Territoriale di Lecco

    Lecco, 23900

  • ASST Ovest Milanese - Presidio Ospedallero di Legnana

    Legnano, 20025

  • Fondazione Toscana Gabriele Monasterio

    Massa, 54100

  • Ospedale San Raffaele

    Milan, 20132

  • Centro Cardiologico Monzino IRCCS

    Milan, 20138

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • Clinica Mediterranea

    Naples, 80122

  • A.A Dei Colli Monaldi UOC Cardiologia Interventistica

    Naples, 80131

  • Azienda Ospedaliera di Padova

    Padova, 35121

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

  • IRCCS Policlinico San Matteo

    Pavia, 27100

  • Centro Cuore Morgagni

    Pedara, 95030

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, 56124

  • IRCCS-ASMN Reggio Emilia

    Reggio Emilia, 42123

  • AO San Camillo Forlanini

    Rome, 00152

  • Azienda Ospedaliero-Universitaria Policlinico Umberto I

    Rome, 00161

  • AOU Careggi, Interventistica Cardiologica Strutturale

    Rome, 00187

  • Ospedale Sant'Andrea - U.O.S. Emodinamica Cardiologia Interventistica

    Rome, 00189

  • Istituto Clinico Humanitas

    Rozzano, 20089

  • AOU S.Giovanni Di Dio e Ruggi D'Aragona

    Salerno, 84133

  • IRCCS Policlinico San Donato

    San Donato Milanese

  • UOC Emodinamica III

    Siena, 53100

  • Azienda Ospedaliera Integrata di Verona

    Verona, 37126

Other trials in Italy

Germany29 sites

  • Kerckhoff-Klinik

    Bad Nauheim, 61231

  • Herz und Gefaess Klinik

    Bad Neustadt an der Saale, 97616

  • Segeberger Kliniken

    Bad Segeberg, 23795

  • Charite Universitatsmedizin Berlin

    Berlin, 12200

  • Immanuel Klinikum Bernau Herzzentrum Brandenburg

    Berlin, 16321

  • Gesundheit Nord gGmbH

    Bremen, 28277

  • Klinikum der Stadt Ludwigshafen

    Dortmund, 44137

  • St. Johannes - Hospital

    Dortmund, 44137

  • Heart Center Dresden, University Clinic Technical University Dresden

    Dresden, 01307

  • Universitätsklinikum Düsseldorf

    Düsseldorf, 40225

  • Elisabeth Krankenhaus Essen Klinik fur Kardiologie und Angiologie

    Essen, 45138

  • Klinikum Fulda gAG

    Fulda, 36043

  • Universitatsklinikum Halle (Saale)

    Halle, 06120

  • Asklepios St. Georg Abteilung fuer Kardiologie

    Hamburg, 20099

  • Heidelberg University Hospital

    Heidelberg, 69120

  • Universitaetsklinik Schleswig-Holstein Campus Kiel

    Kiel, 24105

  • MediClin Herzzentrum Lahr/Baden

    Lahr, 77933

  • Herzzentrum Leipzig

    Leipzig, 4289

  • Universitatsmedizin Mainz, Zentrum fur Kardiologie

    Mainz, 55131

  • Deutsches Herzzentrum Munchen

    München, 80636

  • Universitatsklinikum Essen, Klinik fur Kardiologie

    München, 81379

  • Klinikum rechts der Isar der Technischen Universitat Munchen

    München, 81675

  • Klinikum Oldenburg AöR

    Oldenburg, 26133

  • Uniklinikum Regensburg, Med II

    Regensburg, 93042

  • Krankenhaus der Barmherzigen

    Trier, 54292

  • Universitaetsklinikum Tuebingen Medizinische Klinik, Abteilung III

    Tübingen, 72076

  • Universitatsklinikum Ulm

    Ulm, 89081

  • Helios Herzzentrum Wuppertal

    Wuppertal, 42117

  • Universitatsklinikum Wurzburg

    Würzburg, 97080

Other trials in Germany

Spain22 sites

  • Complexo Hospitalario Universitario de A Coruna

    A Coruña, 15006

  • Complexo hospitalario universitario de Santiago de Compostela

    A Coruña, 15706

  • Hospital General Universitario de Alicante

    Alicante, 03540

  • Hospital Universitari Germans Trias I Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinico y Provincial de Barcelona

    Barcelona, 08036

  • Hospital Universitario Donostia

    Donostia / San Sebastian, Gipuzkoa, 20014

  • Complejo Asistencial de Granada

    Granada, 18014

  • Hospital La Luz QuironSalud

    Madrid, 28003

  • Hospital Universitario La Princesa

    Madrid, 28006

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Virgen de la Arrixaca

    Murcia, 31020

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33011

  • Valdecilla Hospital

    Santander, 39008

  • Hospital Universitario Virgen Macarena

    Seville, Andalusia, 41009

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clinico de Valencia

    Valencia, 46010

  • Hospital Clinico Universitario de Valladolid

    Valladolid, 47003

  • Hospital Universitario Alvaro Cunqueiro

    Vigo, 36312

Other trials in Spain

Japan18 sites

  • Osaka City University Hospital

    Abeno Ward, Osaka, 545-8586

  • Toyohashi Heart Center

    Aichi, 441-8530

  • Tsukuba Medical Center Hospital

    Amakubo, Ibaraki, 305-8558

  • New Tokyo Hospital

    Chiba, 270-2232

  • Tokai University Hospital

    Isehara, Kanagawa, 259-1193

  • Shonan Kamakura General Hospital

    Kanagawa, 247-0072

  • St. Marianna University School of Medicine Hospital

    Kawasaki, Kanagawa, 216-0015

  • Kishiwada Tokushukai Hospital

    Kishiwada, Osaka, 596-0042

  • Kokura Memorial Hospital

    Kitakyushu, Fukuoka, 802-8555

  • Iwate Medical University Hospital

    Morioka, Iwate, 020-8505

  • Ogaki Municipal Hospital

    Ōgaki, Gifu, 503-0864

  • Sapporo Higashi Tokushukai Hospital

    Sapporo, Hokkaido, 065-0033

  • Sendai Kousei Hospital

    Sendai, Miyagi, 980-0873

  • Keio University Hospital

    Shinjuku, Tokyo, 160-0016

  • Teikyo University Hospital

    Tokyo, Itabashi, 173-0003

  • Toyama University Hospital

    Toyama, 930-0194

  • Nagoya Heart Center

    Toyohashi, Aichi-ken, 441-8530

  • Saiseikai Yokohamashi Tobu Hospital

    Yokohama, Kanagawa, 230-8765

Other trials in Japan

France13 sites

  • CHU d'Angers

    Angers

  • Clinique Saint Augustin

    Bordeaux, 33074

  • Hopital Henri Mondor

    Créteil, 94000

  • Institut Coeur Poumon - CHRU de Lille

    Lille, 59000

  • CHU Arnaud de Villeneuve

    Montpellier, 34295

  • Clinique du Millenaire Service de Cardiologie Interventionelle

    Montpellier, 34960

  • Institut Mutualiste Montsouris

    Paris, 75014

  • Hopital Bichat

    Paris, 75877

  • CHU de Bordeaux Hopital du Haut Leveque

    Pessac, 33604

  • CHU de Rouen

    Rouen, 76000

  • Clinique Saint-Hilaire

    Rouen, 76000

  • Nouvel Hopital Civil

    Strasbourg, 67091

  • Clinique Pasteur / GCVI

    Toulouse, 31300

Other trials in France

Canada10 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2R7

  • Hamilton General Hospital

    Hamilton, L8L 2X2

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • Newmarket Cardiac Surgery Research Incorporated

    Newmarket, Ontario, L3Y 3S9

  • Universitè Laval

    Québec, G1V 4G5

  • Horizon Health Network

    Saint John, E2L4L2

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • University Health Network

    Toronto, Ontario, M5G 2C4

Other trials in Canada

United Kingdom10 sites

  • BSUH, Cardiac Research Unit

    Brighton, England, BN2 5BE

  • Papworth Hospital NHS Foundation Trust

    Cambridge, England, CB23 3RE

  • University Hospital of Wales, Heath Park

    Cardiff, Wales, CF14 4XW

  • Royal Edinburgh Infirmary

    Edinburgh, England, EH16 4SA

  • University Hospitals of Leicester NHS Trust

    Leicester, LE3 9QP

  • Guys St Thomas Hospital

    London, England, SE1 7EH

  • Trent Cardiac Centre

    Nottingham, England, NG5 1PB

  • Oxford University Hospitals, John Radcliffe Hospital

    Oxford, England, OX3 9DU

  • Derriford Hospital

    Plymouth, PL6 8DH

  • Northern General Hospital

    Sheffield, England, S5 7AU

Other trials in United Kingdom

Belgium8 sites

  • ASZ Aalst - Aalst campus

    Aalst, 9300

  • ZNA - Stuivenberg Ziekenhuis Netwerk Antwerpen

    Antwerp, 2060

  • Hospital Erasme

    Brussels, B-1070

  • UZA - Universtiair Ziekenhuis Antwerpen

    Edegem, 2650

  • ZOL Genk, Campus Sint-Jan

    Genk, 3600

  • Jessa Ziekenhuis- Campus Virga Jessa

    Hasselt, 3500

  • CHU de Liege

    Liège, B-4000

  • AZ Delta Roeselare

    Roeselare, 8800

Other trials in Belgium

Austria7 sites

  • Medizinische Universitaet Graz

    Graz, 8036

  • Clinic Wels-Grieskirchen GmbH

    Grieskirchen, 4710

  • Universitaetsklinik fuer Innere Medizin III

    Innsbruck, 6020

  • Klinikum Klagenfurt am Worthersee

    Klagenfurt, 9020

  • Wilhelminenspital

    Vienna, 1060

  • Universitätsklinik für Innere Medizin II

    Vienna, 1090

  • Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel

    Vienna, 1130

Other trials in Austria

Netherlands5 sites

  • Academic Medical Center

    Amsterdam, 1105 AZ

  • University Medical Center Groningen

    Groningen, 9713 GZ

  • Medisch Centrum Leeuwarden

    Leeuwarden, 8934 AD

  • Erasmus Medical Center

    Rotterdam, 3015 CN

  • HagaZiekenhuis

    The Hague, 2504 LN

Other trials in Netherlands

South Korea5 sites

  • Seoul National University Hospital

    Seoul, Jongno-gu

  • Seoul St. Mary's Hospital

    Seoul, Seocho-gu, 06591

  • Yonsei University Severance Hospital

    Seoul, Seodaemun-gu

  • Korean University Anam Hospital

    Seoul, Seongbuk-gu, 02841

  • Asan Medical Center

    Seoul, Songpa-gu

Other trials in South Korea

Switzerland4 sites

  • Universitatsspital Basel

    Basel, 4031

  • Bern University Hospital

    Bern, 3010

  • Hopitaux Universitaires de Geneve

    Geneva, 1205

  • Cardiocentro Ticino

    Lugano, 6900

Other trials in Switzerland

Poland3 sites

  • Uniwersytecki Szpital Kliniczny w Bialymstoku

    Bialystok, 15-276

  • University Clinical Centre in Gdańsk

    Gdansk, 80-952

  • Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

    Poznan, 61-848

Other trials in Poland

About this study

Official title: 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.

Read the 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).
Being tested
Edoxaban-based Regimen, VKA-based Regimen
Keywords
Transcatheter Aortic Valve Implantation -- TAVI, Anticoagulation, Atrial Fibrillation, ENVISAGE-TAVI-AF
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Edoxaban-based RegimenDrug

    Also called Savaysa, Lixiana

    15 mg, 30 mg and 60 mg film coated tablet for oral use (with anti-platelet therapy pre-declared at randomization if prescribed)

  • VKA-based RegimenDrug

    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).

Study groups in NCT02943785
Study groupRoleWhat they receive
Edoxaban-based RegimenExperimentalEdoxaban-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.
Receives: Drug: Edoxaban-based Regimen
VKA-based RegimenActive comparatorVKA-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.
Receives: Drug: VKA-based Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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].

    Measured: Baseline through study completion, up to 36 months post-dose

  2. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

Secondary outcomes (10)

  1. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  2. 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

    Measured: Baseline through study completion, up to 36 months post-dose

  3. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  4. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  5. 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

    Measured: Baseline through study completion, up to 36 months post-dose

  6. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  7. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  8. 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).

    Measured: Baseline through study completion, up to 36 months post-dose

  9. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

  10. 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.

    Measured: Baseline through study completion, up to 36 months post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2016 (estimated)
  2. Study start21 Mar 2017
  3. Primary completion28 Feb 2021
  4. Study completion28 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,426 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02943785
Sponsor's protocol ID
DU176B-C-U4001
Other IDs
2016-003930-26, 2016
Status last verified
Mar 2022
First submitted
21 Oct 2016
Last updated
24 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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/

Publications

  • Van Mieghem NM, Chen C, Hengstenberg C, Van Zyl J, Kimura T, Lang I, Mehran R, Nicolas J, Unverdorben M, Zamorano JL, Dangas GD. Edoxaban Dose Adjustment and Age-Associated Outcomes in Patients With Atrial Fibrillation Post-Transcatheter Aortic Valve Replacement. JACC Adv. 2025 Dec;4(12 Pt 1):102329. doi: 10.1016/j.jacadv.2025.102329. Epub 2025 Nov 19.

    PubMed 41263742

  • Dangas GD, Unverdorben M, Nicolas J, Hengstenberg C, Chen C, Mollmann H, Jin J, Shawl F, Yamamoto M, Saito S, Hambrecht R, Duggal A, Van Mieghem NM. Comparing Major Gastrointestinal Bleeding in Patients Receiving Edoxaban Versus Warfarin After Transcatheter Aortic Valve Replacement: Results From the Randomized ENVISAGE-TAVI AF Trial. J Am Heart Assoc. 2025 May 20;14(10):e033321. doi: 10.1161/JAHA.123.033321. Epub 2025 May 15.

    PubMed 40371611

  • 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.

    PubMed 34449183

  • 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.

    PubMed 34274293

  • 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.

    PubMed 30172099

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Edoxaban-based Regimen and VKA-based Regimen in people with Atrial Fibrillation, run by Daiichi Sankyo at 230 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 230 sites in United States, Italy, Germany, Spain, Japan and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Net Adverse Clinical Events (Adjudicated Data) Based on ISTH Criteria in Participants Taking Edoxaban vs VKA (time frame: Baseline through study completion, up to 36 months post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02943785, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2022.

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