Edoxaban vs. Warfarin in Subjects Undergoing Cardioversion of Nonvalvular Atrial Fibrillation (NVAF) (ENSURE-AF)

March 13, 2019 updated by: Daiichi Sankyo, Inc.

A Prospective, Randomized, Open-Label Blinded Endpoint Evaluation (PROBE) Parallel Group Study Comparing Edoxaban (DU-176b) With Enoxaparin/Warfarin Followed by Warfarin Alone in Subjects Undergoing Planned Electrical Cardioversion of Nonvalvular Atrial Fibrillation

The purpose of this study is to compare edoxaban to warfarin (with enoxaparin, if needed). It will see if edoxaban prevents stroke and other blood clotting problems as well and as safely as warfarin. People with atrial fibrillation (irregular heartbeat) might be able to join. Their doctors must plan to use shock to make their hearts beat normally. About 2200 people from different countries will join. They will have an equal chance of receiving either treatment. They are anticipated to be in the study for around 82 days. Tests will include physicals and finger-pricks. Participants will provide blood and urine samples.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to compare edoxaban (investigational drug) with warfarin and enoxaparin, to see if it is safe and effective in preventing stroke and other blood clot complications in subjects with atrial fibrillation whose doctors plan to treat them with an electrical cardioversion. It is expected that 284 sites will recruit 2200 subjects from North America, EU, Russia, Ukraine and Israel. Participants will be randomly allocated to receive either treatment with edoxaban, or treatment with warfarin, plus enoxaparin if required. Participants will have an equal chance of receiving either treatment. Participants will be in the study for a maximum of 82 days. Study procedures will include physical examinations, vital signs (pulse and sitting blood pressure), ECG (electrocardiogram), finger prick blood clotting tests, blood samples and urine samples.

The study is expected to show that edoxaban will provide comparable incidence rates to warfarin plus enoxaparin, the current standard treatment for both efficacy and bleeding.

Study Type

Interventional

Enrollment (Actual)

2199

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria
      • Innsbruck, Austria
      • Linz, Austria
      • Modling, Austria
      • Wien, Austria
  • Belgium
      • Brussels, Belgium
      • Genk, Belgium
      • Gent, Belgium
      • Hasselt, Belgium
      • Huy, Belgium
      • Leuven, Belgium
      • Liege, Belgium
      • Mechelen, Belgium
      • Tienen, Belgium
      • Turnhout, Belgium
  • Bulgaria
      • Burgas, Bulgaria
      • Gabrovo, Bulgaria
      • Pazardzhik, Bulgaria
      • Pleven, Bulgaria
      • Plovdiv, Bulgaria
      • Sofia, Bulgaria
      • Stara Zagora, Bulgaria
      • Varna, Bulgaria
      • Veliko Tarnovo, Bulgaria
  • Czechia
      • Brno, Czechia
      • Cesky Krumlov, Czechia
      • Havlickuv Brod, Czechia
      • Hodonin, Czechia
      • Kolin, Czechia
      • Kromeriz, Czechia
      • Nachod, Czechia
      • Praha 4, Czechia
      • Praha 6, Czechia
      • Pribram, Czechia
      • Slany, Czechia
  • Denmark
      • Aalborg, Denmark
      • Copenhagen, Denmark
        • First site in
      • Copenhagen, Denmark
        • Second site in
      • Frederiksberg, Denmark
      • Hellerup, Denmark
      • Herning, Denmark
      • Holbaek, Denmark
      • Køge, Denmark
      • Silkeborg, Denmark
      • Slagelse, Denmark
      • Svendborg, Denmark
      • Vejle, Denmark
      • Viborg, Denmark
  • France
      • Angers cedex 9, France
      • Bordeaux, France
      • Bron cedex, France
      • Corbeil Essonnes, France
      • Dijon cedex, France
      • Grenoble cedex 09, France
      • Lyon, France
      • Marseille cedex 20, France
      • Marseille cedex 5, France
      • Montfermeil, France
      • Montpellier Cedex 5, France
      • Nice, France
      • Paris, France
      • Saint-Denis cedex, France
      • Toulouse cedex 9, France
      • Vandoeuvre les Nancy cedex, France
  • Germany
      • Bad Berka, Germany
      • Berlin, Germany
      • Bielefeld, Germany
      • Coburg, Germany
      • Dortmund, Germany
      • Dresden, Germany
      • Freiburg, Germany
      • Giessen, Germany
      • Hamburg, Germany
      • Heidelberg, Germany
      • Heilbronn, Germany
        • Bad Friedrichshall
      • Langen, Germany
      • Leipzig, Germany
      • Ludwigsburg, Germany
      • Mainz, Germany
      • Marburg, Germany
      • Monchengladbach, Germany
      • Munchen, Germany
      • Paderborn, Germany
      • Regensburg, Germany
  • Hungary
      • Balatonfured, Hungary
      • Budapest, Hungary
        • First site in
      • Budapest, Hungary
        • Second site in
      • Cegled, Hungary
      • Debrecen, Hungary
      • Gyula, Hungary
      • Győr, Hungary
      • Hodmezovasarhely, Hungary
      • Kecskemet, Hungary
      • Nagykanizsa, Hungary
      • Pécs, Hungary
      • Szeged, Hungary
      • Szekesfehervar, Hungary
      • Szolnok, Hungary
      • Szombathely, Hungary
      • Zalaegerszeg, Hungary
  • Israel
      • Afula, Israel
      • Ashkelon, Israel
      • Hadera, Israel
      • Haifa, Israel
      • Holon, Israel
      • Jerusalem, Israel
      • Kfar Saba, Israel
      • Ramat Gan, Israel
      • Tel Aviv, Israel
  • Italy
      • Bologna, Italy
      • Catania, Italy
      • Chieti, Italy
      • Napoli, Italy
      • Pavia, Italy
      • Roma, Italy
        • First site in
      • Roma, Italy
        • Second site in
      • Trieste, Italy
    • BA
      • Acquaviva delle Fonti, BA, Italy
    • CE
      • Santa Maria Capua Vetere, CE, Italy
    • VE
      • Mestre, VE, Italy
  • Netherlands
      • Amsterdam, Netherlands
      • Den Haag, Netherlands
      • Hilversum, Netherlands
      • Leeuwarden, Netherlands
      • Rotterdam, Netherlands
      • Venlo, Netherlands
      • Zwolle, Netherlands
  • Poland
      • Elblag, Poland
      • Krakow, Poland
      • Lodz, Poland
      • Lublin, Poland
      • Pulawy, Poland
      • Torun, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Romania
      • Baia Mare, Romania
      • Braila, Romania
      • Bucuresti, Romania
      • Cluj-Napoca, Romania
      • Iasi, Romania
      • Pitesti, Romania
      • Targoviste, Romania
      • Timisoara, Romania
      • Târgu-Mureş, Romania
    • Bihor
      • Oradea, Bihor, Romania
    • Dolj
      • Craiova, Dolj, Romania
    • Vrancea
      • Focsani, Vrancea, Romania
  • Russian Federation
      • Barnaul, Russian Federation
      • Kemerovo, Russian Federation
      • Moscow, Russian Federation
      • Novosibirsk, Russian Federation
      • Saint-Petersburg, Russian Federation
      • Tyumen, Russian Federation
      • Yaroslavl, Russian Federation
  • Spain
      • Almeria, Spain
      • Barcelona, Spain
        • First site in
      • Barcelona, Spain
        • Second site in
      • Granada, Spain
      • Lugo, Spain
      • Madrid, Spain
        • First site in
      • Madrid, Spain
        • Second site in
      • Madrid, Spain
        • Third site in
      • Ourense, Spain
      • Santiago de Compostela, Spain
      • Valencia, Spain
      • Vigo, Spain
    • Alicante
      • San Juan de Alicante, Alicante, Spain
    • Barcelona
      • Sabadell, Barcelona, Spain
    • Girona
      • Salt, Girona, Spain
  • Sweden
      • Helsingborg, Sweden
      • Uppsala, Sweden
  • Ukraine
      • Cherkasy, Ukraine
      • Ivano-Frankivsk, Ukraine
      • Kharkiv, Ukraine
      • Kyiv, Ukraine
      • Odesa, Ukraine
      • Uzhhorod, Ukraine
      • Vinnytsia, Ukraine
      • Zaporizhzhia, Ukraine
      • Zhytomyr, Ukraine
  • United Kingdom
      • Barnet, United Kingdom
      • Basildon, United Kingdom
      • Birmingham, United Kingdom
      • Bournemouth, United Kingdom
      • Bradford, United Kingdom
      • Chertsey, United Kingdom
      • Doncaster, United Kingdom
      • Dundee, United Kingdom
      • Harrow, United Kingdom
      • Leeds, United Kingdom
      • Leicester, United Kingdom
      • Liverpool, United Kingdom
      • Llanelli, United Kingdom
      • London, United Kingdom
      • Luton, United Kingdom
      • Newport, United Kingdom
      • Oxford, United Kingdom
      • Plymouth, United Kingdom
      • Swansea, United Kingdom
    • Essex
      • Romford, Essex, United Kingdom
    • Hampshire
      • Southampton, Hampshire, United Kingdom
    • Lancashire
      • Blackpool, Lancashire, United Kingdom
  • United States
    • Arizona
      • Phoenix, Arizona, United States
    • California
      • Escondido, California, United States
      • Newport Beach, California, United States
      • Riverside, California, United States
      • San Francisco, California, United States
      • Santa Rosa, California, United States
    • Colorado
      • Denver, Colorado, United States
    • Connecticut
      • Stamford, Connecticut, United States
    • Delaware
      • Newark, Delaware, United States
    • Florida
      • Clearwater, Florida, United States
      • Daytona Beach, Florida, United States
      • Jupiter, Florida, United States
      • Rockledge, Florida, United States
      • Sarasota, Florida, United States
      • Tampa, Florida, United States
    • Idaho
      • Boise, Idaho, United States
    • Maine
      • Auburn, Maine, United States
    • Minnesota
      • Rochester, Minnesota, United States
    • Pennsylvania
      • Allentown, Pennsylvania, United States
      • Butler, Pennsylvania, United States
      • Camp Hill, Pennsylvania, United States
      • Hershey, Pennsylvania, United States
    • Tennessee
      • Jackson, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Fort Worth, Texas, United States
      • Plano, Texas, United States
      • Tyler, Texas, United States
    • Virginia
      • Richmond, Virginia, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Has signed informed consent
  • Is older than minimum legal adult age (country specific)
  • Has had ongoing AF lasting at least 48 hrs but <= 12 months (with or without valvular heart disease)
  • Has treatment plan that includes for electrical cardioversion
  • Has NVAF or other specific valvular heart diseases (eg, mitral valve prolapse, mitral valve regurgitation, and aortic valve disease)

Exclusion Criteria:

  • Has AF that is transient or reversible
  • Has contraindicated condition, ie, conditions considered to be formal indication for conventional anticoagulation
  • Has a history of left atrial appendage (LAA) closure
  • Has a known thrombus in LAA, the left atrial, left ventricle or aorta - or an intracardial mass
  • Has had myocardial infarction (MI), stroke, acute coronary syndrome (ACS), or percutaneous coronary intervention (PCI) within the past 30 days
  • Has any contraindication to anticoagulant agents
  • Has had protocol-defined signs of bleeding or conditions associated with high risk of bleeding that would preclude participation
  • Is receiving, or plans to receive during the study period, dual antiplatelet therapy (DAPT) or invasive procedures (other than routine endoscopy) in which bleeding would be anticipated
  • Has received prohibited concomitant medication or therapy
  • Has had protocol-defined signs of bleeding or high
  • Has inadequate liver, kidney, and blood test results
  • Received any investigational drug or device within the past 30 days or plans to during the study period
  • Has reproductive potential and does not agree to take proper contraceptive measures
  • Has active cancer requiring chemotherapy/radiation/major surgery within the next 3 months
  • Has significant active concurrent medical illness or infection or life expectancy less than 6 months
  • In the opinion of the investigator, is unlikely to comply with the protocol or complete the study, has had drug or alcohol dependence within the past year, or has any other condition that might place the participant at increased risk of harm
  • Is a participant in the United States after January 2015 with creatinine clearance (CrCL) greater than 95 mL/minute

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Edoxaban
Edoxaban oral tablet, 60 mg-once daily (QD), reduced to 30 mg based on protocol-defined parameters, for up to 49 days
Drug: Edoxaban
Edoxaban 30 mg tablets for oral administration
ACTIVE_COMPARATOR: Warfarin

Participants naïve to anticoagulation, taking anticoagulants other than a Vitamin K antagonist (VKA) or taking a VKA but with a prothrombin time (PT) international normalized ratio (INR) of less than 2.0 receive enoxaparin until they reach a PT INR of at least 2.0, before taking warfarin.

All participants in this arm receive warfarin oral tablet QD at their doctor's prescribed dose, for up to 49 days.
Drug: Warfarin
Warfarin tablet, 1.0 or 2.5 mg, for oral administration
Drug: Enoxaparin
Enoxaparin per label, at prescribed dose until PT INR at least 2.0

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants With Composite Endpoint of Stroke, Systemic Embolic Stroke (SEE), Myocardial Infarction (MI) and Cardiovascular (CV) Mortality From Randomization to End of Follow up
Time Frame: Randomization to end of follow-up (within 2 years)
Randomization to end of follow-up (within 2 years)
Percentage of Participants With Composite Endpoints of Major and Clinically-relevant Non-major (CRNM) Bleeding
Time Frame: During treatment period (within 2 years)
During treatment period (within 2 years)

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants With Composite Endpoints of Stroke, SEE, MI, CV Mortality, and Major Bleeding
Time Frame: From randomization to the end of follow-up (within 2 years)
From randomization to the end of follow-up (within 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daiichi Sankyo, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 25, 2014

Primary Completion (ACTUAL)

February 3, 2016

Study Completion (ACTUAL)

February 3, 2016

Study Registration Dates

First Submitted

February 20, 2014

First Submitted That Met QC Criteria

February 24, 2014

First Posted (ESTIMATE)

February 26, 2014

Study Record Updates

Last Update Posted (ACTUAL)

March 15, 2019

Last Update Submitted That Met QC Criteria

March 13, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DU176b-F-E308
  • 2013-003148-21 (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

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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