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

Atrial Fibrillation Clinical Trial

— ENSURE-AF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072434
• Other study ID #: DU176b-F-E308
• Secondary ID: 2013-003148-21
• Status: Completed
• Phase: Phase 3
• Start date: March 25, 2014
• Est. completion date: February 3, 2016

Study information

• Verified date: March 2019
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2199
• Est. completion date: February 3, 2016
• Est. primary completion date: February 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Edoxaban
Edoxaban 30 mg tablets for oral administration
• Warfarin
Warfarin tablet, 1.0 or 2.5 mg, for oral administration
• Enoxaparin
Enoxaparin per label, at prescribed dose until PT INR at least 2.0

Locations

Country	Name	City	State
Denmark	First site in	Copenhagen
Denmark	Second site in	Copenhagen
Germany	Bad Friedrichshall	Heilbronn
Hungary	First site in	Budapest
Hungary	Second site in	Budapest
Italy	First site in	Roma
Italy	Second site in	Roma
Spain	First site in	Barcelona
Spain	Second site in	Barcelona
Spain	First site in	Madrid
Spain	Second site in	Madrid
Spain	Third site in	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (1)

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Percentage of Participants With Composite Endpoints of Major and Clinically-relevant Non-major (CRNM) Bleeding		During treatment period (within 2 years)
Secondary	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)