Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate

Study Overview
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Brief Summary
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The primary objective of this trial is to demonstrate the efficacy and safety of dabigatran etexilate in patients with non-valvular atrial fibrillation for the prevention of stroke and systemic embolism.

Official Title
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Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) Comparing the Efficacy and Safety of Two Blinded Doses of Dabigatran Etexilate With Open Label Warfarin for the Prevention of Stroke and Systemic Embolism in Patients With Non-valvular Atrial Fibrillation: Prospective, Multi-centre, Parallel-group, Non-inferiority Trial (RE-LY Study)

Conditions
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Atrial Fibrillation, Stroke

Intervention / Treatment
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* Drug: warfarin
* Drug: Dabigatran dose 1
* Drug: Dabigatran dose 2


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients with non-valvular atrial fibrillation (AF), at moderate to high risk of stroke, or systemic embolism with at least one additional risk factor (i.e. previous ischemic stroke, TIA, or systemic embolism, left ventricular dysfunction, age >=75 years, age >=65 with either diabetes mellitus, history of coronary artery disease or hypertension) Exclusion criteria Prosthetic heart valves requiring anticoagulation per se, or hemodynamically relevant valve disease that is expected to require surgical intervention during the course of the study Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days Conditions associated with an increased risk of bleeding Contraindication to warfarin treatment Reversible causes of atrial fibrillation (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). Plan to perform a pulmonary vein ablation or surgery for cure of the AF Severe renal impairment (estimated creatinine clearance <=30 mL/min) Active infective endocarditis Active liver disease Women who are pregnant, lactating, or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study Anaemia (haemoglobin <100g/L) or thrombocytopenia (platelet count <100 x 109/L) Patients who have developed transaminase elevations upon exposure to ximelagatran Patients who have received an investigational drug in the past 30 days or are participating in another drug study Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, has a life expectancy less than the expected duration of the trial due to concomitant disease, or has any condition which in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse) Any known hypersensitivity to galactose if the warfarin used contains galactose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dabigatran dose 2<br>twice a day | Drug: Dabigatran dose 2<br>* twice a day<br>|
| Active Comparator: Warfarin<br>once a day | Drug: warfarin<br>* once a day<br>|
| Active Comparator: Dabigatran dose 1<br>twice a day | Drug: Dabigatran dose 1<br>* twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yearly Event Rate for Composite Endpoint of Stroke/SEE | Time to first occurrence of stroke or systemic embolic event. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum(date of study termination - date of randomization + 1) of all randomized subjects / 365.25 | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yearly Event Rate for Composite Endpoint of Stroke/SEE/All Cause Death | Time to first occurrence of stroke, SEE or all cause death. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum(date of study termination - date of randomization + 1) of all randomized subjects / 365.25 | 36 months | 
| Yearly Event Rate: Composite of Stroke/SEE/PE/MI/Vascular Death | Time to first occurrence of stroke, systemic embolic event, pulmonary embolism, myocardial infarction including silent myocardial infarction or vascular death. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum(date of study termination - date of randomization + 1) of all randomized subjects / 365.25 | 36 months | 
| Bleeding Events (Major and Minor) | Yearly event rate of bleeds. Yearly event rate (%) = number of subjects with event / subject-years * 100. Subject years = sum(date of study termination - date of randomization + 1) of all randomized subjects / 365.25 Major bleeds are adjudicated, whereas minor bleeds are investigator reported. | 36 months | 
| Clinical Relevant Abnormalities for Intracerebral Hemorrhage and Other Intracranial Hemorrhage (ICH) | Patients with clinical relevant abnormalities for intracerebral hemorrhage, other intracranial hemorrhage (ICH) | 36 months | 
| Abnormal Liver Function Test | Number of subjects with abnormal liver function test (LFT), i.e., ALT/AST>3xULN and total bilirubin > 2 x ULN | 36 months |