Edoxaban vs. Warfarin in Subjects Undergoing Cardioversion of Nonvalvular Atrial Fibrillation (NVAF)
ENSURE-AF
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
2 other identifiers
interventional
2,199
19 countries
228
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 atrial-fibrillation
Started Mar 2014
Shorter than P25 for phase_3 atrial-fibrillation
228 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 20, 2014
CompletedFirst Posted
Study publicly available on registry
February 26, 2014
CompletedStudy Start
First participant enrolled
March 25, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 3, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
February 3, 2016
CompletedResults Posted
Study results publicly available
March 13, 2019
CompletedMarch 15, 2019
March 1, 2019
1.9 years
February 20, 2014
January 30, 2019
March 13, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Randomization to end of follow-up (within 2 years)
Percentage of Participants With Composite Endpoints of Major and Clinically-relevant Non-major (CRNM) Bleeding
During treatment period (within 2 years)
Secondary Outcomes (1)
Percentage of Participants With Composite Endpoints of Stroke, SEE, MI, CV Mortality, and Major Bleeding
From randomization to the end of follow-up (within 2 years)
Study Arms (2)
Edoxaban
EXPERIMENTALEdoxaban oral tablet, 60 mg-once daily (QD), reduced to 30 mg based on protocol-defined parameters, for up to 49 days
Warfarin
ACTIVE COMPARATORParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Daiichi Sankyolead
Study Sites (228)
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Phoenix, Arizona, United States
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Escondido, California, United States
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Newport Beach, California, United States
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Riverside, California, United States
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San Francisco, California, United States
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Santa Rosa, California, United States
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Denver, Colorado, United States
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Stamford, Connecticut, United States
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Newark, Delaware, United States
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Clearwater, Florida, United States
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Daytona Beach, Florida, United States
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Jupiter, Florida, United States
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Rockledge, Florida, United States
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Sarasota, Florida, United States
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Tampa, Florida, United States
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Boise, Idaho, United States
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Auburn, Maine, United States
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Rochester, Minnesota, United States
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Allentown, Pennsylvania, United States
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Butler, Pennsylvania, United States
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Camp Hill, Pennsylvania, United States
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Hershey, Pennsylvania, United States
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Jackson, Tennessee, United States
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Plano, Texas, United States
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Tyler, Texas, United States
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Richmond, Virginia, United States
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Graz, Austria
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Innsbruck, Austria
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Linz, Austria
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Mödling, Austria
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Vienna, Austria
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Brussels, Belgium
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Genk, Belgium
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Ghent, Belgium
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Hasselt, Belgium
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Huy, Belgium
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Leuven, Belgium
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Liège, Belgium
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Mechelen, Belgium
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Tienen, Belgium
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Turnhout, Belgium
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Burgas, Bulgaria
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Gabrovo, Bulgaria
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Pazardzhik, Bulgaria
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Pleven, Bulgaria
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Plovdiv, Bulgaria
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Sofia, Bulgaria
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Stara Zagora, Bulgaria
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Varna, Bulgaria
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Veliko Tarnovo, Bulgaria
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Brno, Czechia
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Český Krumlov, Czechia
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Havlíčkův Brod, Czechia
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Hodonín, Czechia
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Kolín, Czechia
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Kroměříž, Czechia
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Náchod, Czechia
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Prague, Czechia
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Příbram, Czechia
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Slaný, Czechia
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Aalborg, Denmark
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Copenhagen, Denmark
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Copenhagen, Denmark
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Frederiksberg, Denmark
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Hellerup, Denmark
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Herning, Denmark
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Holbæk, Denmark
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Køge, Denmark
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Silkeborg, Denmark
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Slagelse, Denmark
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Svendborg, Denmark
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Vejle, Denmark
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Viborg, Denmark
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Angers, France
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Bordeaux, France
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Bron, France
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Corbeil-Essonnes, France
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Dijon, France
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Grenoble, France
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Lyon, France
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Marseille, France
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Montfermeil, France
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Montpellier, France
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Nice, France
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Paris, France
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Saint-Denis, France
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Toulouse, France
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Vandœuvre-lès-Nancy, France
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Bad Berka, Germany
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Berlin, Germany
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Bielefeld, Germany
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Coburg, Germany
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Dortmund, Germany
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Dresden, Germany
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Freiburg im Breisgau, Germany
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Giessen, Germany
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Hamburg, Germany
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Heidelberg, Germany
Bad Friedrichshall
Heilbronn, Germany
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Langen, Germany
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Leipzig, Germany
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Ludwigsburg, Germany
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Mainz, Germany
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Marburg, Germany
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Mönchengladbach, Germany
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München, Germany
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Paderborn, Germany
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Regensburg, Germany
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Balatonfüred, Hungary
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Budapest, Hungary
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Cegléd, Hungary
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Debrecen, Hungary
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Győr, Hungary
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Gyula, Hungary
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Hódmezővásárhely, Hungary
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Kecskemét, Hungary
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Nagykanizsa, Hungary
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Pécs, Hungary
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Szeged, Hungary
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Székesfehérvár, Hungary
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Szolnok, Hungary
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Szombathely, Hungary
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Zalaegerszeg, Hungary
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Afula, Israel
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Hadera, Israel
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Haifa, Israel
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Holon, Israel
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Jerusalem, Israel
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Kfar Saba, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Acquaviva delle Fonti, BA, Italy
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Santa Maria Capua Vetere, CE, Italy
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Mestre, VE, Italy
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Bologna, Italy
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Catania, Italy
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Chieti, Italy
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Napoli, Italy
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Pavia, Italy
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Roma, Italy
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Trieste, Italy
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Amsterdam, Netherlands
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Hilversum, Netherlands
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Leeuwarden, Netherlands
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Rotterdam, Netherlands
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The Hague, Netherlands
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Venlo, Netherlands
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Zwolle, Netherlands
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Elblag, Poland
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Krakow, Poland
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Lodz, Poland
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Lublin, Poland
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Puławy, Poland
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Torun, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Oradea, Bihor County, Romania
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Craiova, Dolj, Romania
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Focşani, Vrancea, Romania
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Baia Mare, Romania
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Brăila, Romania
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Bucharest, Romania
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Cluj-Napoca, Romania
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Iași, Romania
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Piteşti, Romania
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Târgovişte, Romania
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Târgu Mureş, Romania
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Timișoara, Romania
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Barnaul, Russia
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Kemerovo, Russia
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Moscow, Russia
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Novosibirsk, Russia
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Saint Petersburg, Russia
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Tyumen, Russia
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Yaroslavl, Russia
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Sant Joan d'Alacant, Alicante, Spain
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Sabadell, Barcelona, Spain
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Salt, Girona, Spain
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Almería, Spain
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Barcelona, Spain
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Barcelona, Spain
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Granada, Spain
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Lugo, Spain
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Madrid, Spain
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Madrid, Spain
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Madrid, Spain
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Ourense, Spain
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Santiago de Compostela, Spain
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Valencia, Spain
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Vigo, Spain
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Helsingborg, Sweden
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Uppsala, Sweden
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Cherkasy, Ukraine
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Ivano-Frankivsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Odesa, Ukraine
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Uzhhorod, Ukraine
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Vinnytsia, Ukraine
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Zaporizhzhia, Ukraine
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Zhytomyr, Ukraine
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Romford, Essex, United Kingdom
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Southampton, Hampshire, United Kingdom
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Blackpool, Lancashire, United Kingdom
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Barnet, United Kingdom
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Basildon, United Kingdom
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Birmingham, United Kingdom
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Bournemouth, United Kingdom
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Bradford, United Kingdom
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Chertsey, United Kingdom
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Doncaster, United Kingdom
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Dundee, United Kingdom
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Harrow, United Kingdom
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Leeds, United Kingdom
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Leicester, United Kingdom
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Liverpool, United Kingdom
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Llanelli, United Kingdom
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London, United Kingdom
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Luton, United Kingdom
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Newport, United Kingdom
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Oxford, United Kingdom
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Plymouth, United Kingdom
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Swansea, United Kingdom
Related Publications (4)
Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.
PMID: 24251359BACKGROUNDGoette A, Kwong WJ, Ezekowitz MD, Banach M, Hjortshoj SP, Zamoryakhin D, Lip GYH. Edoxaban therapy increases treatment satisfaction and reduces utilization of healthcare resources: an analysis from the EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) study. Europace. 2018 Dec 1;20(12):1936-1943. doi: 10.1093/europace/euy141.
PMID: 29947751DERIVEDGoette A, Merino JL, Ezekowitz MD, Zamoryakhin D, Melino M, Jin J, Mercuri MF, Grosso MA, Fernandez V, Al-Saady N, Pelekh N, Merkely B, Zenin S, Kushnir M, Spinar J, Batushkin V, de Groot JR, Lip GY; ENSURE-AF investigators. Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet. 2016 Oct 22;388(10055):1995-2003. doi: 10.1016/S0140-6736(16)31474-X. Epub 2016 Aug 30.
PMID: 27590218DERIVEDLip GY, Merino J, Ezekowitz M, Ellenbogen K, Zamoryakhin D, Lanz H, Jin J, Al-Saadi N, Mercuri M, Goette A. A prospective evaluation of edoxaban compared to warfarin in subjects undergoing cardioversion of atrial fibrillation: The EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study. Am Heart J. 2015 May;169(5):597-604.e5. doi: 10.1016/j.ahj.2015.02.009. Epub 2015 Feb 21.
PMID: 25965706DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Daiichi Sankyo US Contact for Clinical Trial Results
- Organization
- Daiichi Sankyo, Inc.
Study Officials
- STUDY DIRECTOR
Global Clinical Leader
Daiichi Sankyo
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 20, 2014
First Posted
February 26, 2014
Study Start
March 25, 2014
Primary Completion
February 3, 2016
Study Completion
February 3, 2016
Last Updated
March 15, 2019
Results First Posted
March 13, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- 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.
- 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.
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/