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

NCT ID: NCT02072434

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-25
• Study Completion Date: 2016-02-03

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.

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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Edoxaban

Edoxaban oral tablet, 60 mg-once daily (QD), reduced to 30 mg based on protocol-defined parameters, for up to 49 days

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

Edoxaban 30 mg tablets for oral administration

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.

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

Warfarin tablet, 1.0 or 2.5 mg, for oral administration

Enoxaparin

Intervention Type: DRUG

Enoxaparin per label, at prescribed dose until PT INR at least 2.0

Interventions

Edoxaban

Edoxaban 30 mg tablets for oral administration

Intervention Type: DRUG

Warfarin

Warfarin tablet, 1.0 or 2.5 mg, for oral administration

Intervention Type: DRUG

Enoxaparin

Enoxaparin per label, at prescribed dose until PT INR at least 2.0

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Phoenix, Arizona, United States

Escondido, California, United States

Newport Beach, California, United States

Riverside, California, United States

San Francisco, California, United States

Santa Rosa, California, United States

Denver, Colorado, United States

Stamford, Connecticut, United States

Newark, Delaware, United States

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

Boise, Idaho, United States

Auburn, Maine, United States

Rochester, Minnesota, United States

Allentown, Pennsylvania, United States

Butler, Pennsylvania, United States

Camp Hill, Pennsylvania, United States

Hershey, Pennsylvania, United States

Jackson, Tennessee, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Plano, Texas, United States

Tyler, Texas, United States

Richmond, Virginia, United States

Graz, , Austria

Innsbruck, , Austria

Linz, , Austria

Mödling, , Austria

Vienna, , Austria

Brussels, , Belgium

Genk, , Belgium

Ghent, , Belgium

Hasselt, , Belgium

Huy, , Belgium

Leuven, , Belgium

Liège, , Belgium

Mechelen, , Belgium

Tienen, , Belgium

Turnhout, , Belgium

Burgas, , Bulgaria

Gabrovo, , Bulgaria

Pazardzhik, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Stara Zagora, , Bulgaria

Varna, , Bulgaria

Veliko Tarnovo, , Bulgaria

Brno, , Czechia

Český Krumlov, , Czechia

Havlíčkův Brod, , Czechia

Hodonín, , Czechia

Kolín, , Czechia

Kroměříž, , Czechia

Náchod, , Czechia

Prague, , Czechia

Příbram, , Czechia

Slaný, , Czechia

Aalborg, , Denmark

First site in

Copenhagen, , Denmark

Second site in

Copenhagen, , Denmark

Frederiksberg, , Denmark

Hellerup, , Denmark

Herning, , Denmark

Holbæk, , Denmark

Køge, , Denmark

Silkeborg, , Denmark

Slagelse, , Denmark

Svendborg, , Denmark

Vejle, , Denmark

Viborg, , Denmark

Angers, , France

Bordeaux, , France

Bron, , France

Corbeil-Essonnes, , France

Dijon, , France

Grenoble, , France

Lyon, , France

Marseille, , France

Montfermeil, , France

Montpellier, , France

Nice, , France

Paris, , France

Saint-Denis, , France

Toulouse, , France

Vandœuvre-lès-Nancy, , France

Bad Berka, , Germany

Berlin, , Germany

Bielefeld, , Germany

Coburg, , Germany

Dortmund, , Germany

Dresden, , Germany

Freiburg im Breisgau, , Germany

Giessen, , Germany

Hamburg, , Germany

Heidelberg, , Germany

Bad Friedrichshall

Heilbronn, , Germany

Langen, , Germany

Leipzig, , Germany

Ludwigsburg, , Germany

Mainz, , Germany

Marburg, , Germany

Mönchengladbach, , Germany

München, , Germany

Paderborn, , Germany

Regensburg, , Germany

Balatonfüred, , Hungary

First site in

Budapest, , Hungary

Second site in

Budapest, , Hungary

Cegléd, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Gyula, , Hungary

Hódmezővásárhely, , Hungary

Kecskemét, , Hungary

Nagykanizsa, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Szombathely, , Hungary

Zalaegerszeg, , Hungary

Afula, , Israel

Ashkelon, , Israel

Hadera, , Israel

Haifa, , Israel

Holon, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Acquaviva delle Fonti, BA, Italy

Santa Maria Capua Vetere, CE, Italy

Mestre, VE, Italy

Bologna, , Italy

Catania, , Italy

Chieti, , Italy

Napoli, , Italy

Pavia, , Italy

First site in

Roma, , Italy

Second site in

Roma, , Italy

Trieste, , Italy

Amsterdam, , Netherlands

Hilversum, , Netherlands

Leeuwarden, , Netherlands

Rotterdam, , Netherlands

The Hague, , Netherlands

Venlo, , Netherlands

Zwolle, , Netherlands

Elblag, , Poland

Krakow, , Poland

Lodz, , Poland

Lublin, , Poland

Puławy, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Oradea, Bihor County, Romania

Craiova, Dolj, Romania

Focşani, Vrancea, Romania

Baia Mare, , Romania

Brăila, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Iași, , Romania

Piteşti, , Romania

Târgovişte, , Romania

Târgu Mureş, , Romania

Timișoara, , Romania

Barnaul, , Russia

Kemerovo, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Tyumen, , Russia

Yaroslavl, , Russia

Sant Joan d'Alacant, Alicante, Spain

Sabadell, Barcelona, Spain

Salt, Girona, Spain

Almería, , Spain

First site in

Barcelona, , Spain

Second site in

Barcelona, , Spain

Granada, , Spain

Lugo, , Spain

First site in

Madrid, , Spain

Second site in

Madrid, , Spain

Third site in

Madrid, , Spain

Ourense, , Spain

Santiago de Compostela, , Spain

Valencia, , Spain

Vigo, , Spain

Helsingborg, , Sweden

Uppsala, , Sweden

Cherkasy, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Odesa, , Ukraine

Uzhhorod, , Ukraine

Vinnytsia, , Ukraine

Zaporizhzhia, , Ukraine

Zhytomyr, , Ukraine

Romford, Essex, United Kingdom

Southampton, Hampshire, United Kingdom

Blackpool, Lancashire, 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

Countries

United States; Austria; Belgium; Bulgaria; Czechia; Denmark; France; Germany; Hungary; Israel; Italy; Netherlands; Poland; Romania; Russia; Spain; Sweden; Ukraine; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 24251359 (View on PubMed)

Goette 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.

Reference Type: DERIVED

PMID: 29947751 (View on PubMed)

Goette 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.

Reference Type: DERIVED

PMID: 27590218 (View on PubMed)

Lip 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.

Reference Type: DERIVED

PMID: 25965706 (View on PubMed)

Other Identifiers

2013-003148-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DU176b-F-E308

Identifier Type: -

Identifier Source: org_study_id