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

Daiichi Sankyo

Status and phase: Completed; Phase 3

Conditions: Atrial Fibrillation

Treatments: Drug: Warfarin; Drug: Enoxaparin; Drug: Edoxaban

Study type: Interventional

Funder types: Industry

Identifiers

NCT02072434

2013-003148-21 (EudraCT Number)

DU176b-F-E308

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,199 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,199 participants in 2 patient groups

Edoxaban

Experimental group

Description:

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

Treatment:

Drug: Edoxaban

Warfarin

Active Comparator group

Description:

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.

Treatment:

Drug: Enoxaparin

Drug: Warfarin