Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of abbreviated 3-day anticoagulation with dabigatran etexilate before cardioversion guided by trans-oesophageal echocardiography in comparison with conventional 3- week course of dabigatran etexilate before cardioversion

Detailed Description
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Current guidelines recommend for stroke prevention in patients with atrial fibrillation (AF) lasting more than 48 h designated for cardioversion standard approach with anticoagulation for a minimum 3 weeks before anticoagulation. The alternative is abbreviated anticoagulation in case of using trans-oesophageal echocardiography (TEE)-guided approach with quick cardioversion if no thrombus or high-grade spontaneous echo contrast is seen. There is currently no data on the direct comparison of efficacy and safety of conventional and abbreviated courses of non-vitamin K antagonist oral anticoagulants (NOAC) before cardioversion in AF. The RE-SOUND study is prospective open label study with blinded outcome evaluation (PROBE design) multicenter active control trial comparing efficacy of 3-day abbreviated TEE-guided and conventional 3-week courses of NOAC dabigatran etexilate before cardioversion in adult patients with AF lasting more than 48 h

Official Title
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Prospective Open Label Randomized Evaluation of Abbreviated Course of Dabigatran Etexilate With tranSesophageal echOcardiography (TEE) Control vs Conventional 3-week coUrse With dabigatraN Etexilate Before Cardioversion: Analysis of MRI-detecteD Cerebral Embolism (RE-SOUND Study), № 1160.242

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: dabigatran etexilate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and female subjects aged >18 years old and <75 years old the diagnosis of non-valvular atrial fibrillation/atrial flutter duration of 48 hours or more (or unknown) documented by ECG. Duration of AF will be defined on the base of patient source documents documented physician's decision to conduct electrical cardioversion written informed consent form (ICF) signed by patient Exclusion Criteria: effective treatment with oral anticoagulants within the last 30 days need in anticoagulant treatment for disorder other than AF rheumatic heart disease mitral stenosis of unknown origin mechanic heart valve acute coronary syndrome within 12 months percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery within the last 12 month or planned for the next 8 weeks known hypersensitivity for dabigatran, dabigatran etexilate or to any of capsul's components creatinine clearance <30 ml/min active bleeding, haemorrhagic diathesis, coagulopathy major surgery within the previous month, surgery planned for the next 8 weeks, clinically relevant bleeding within the last 30 days symptomatic or endoscopically documented gastroduodenal ulcers within the last 30 days intracranial haemorrhages in medical history organ damages resulted from clinically relevant bleeding within 6 months before randomization. major trauma or any craniocerebral trauma within 30 days before randomization. any cancer within last 5 years uncontrolled hypertension (systolic blood pressure >180mm Hg and/or diastolic blood pressure >100 mmHg). chronic heart failure (CHF) III-IV functional classes (by NYHA) severe ischemic stroke within the last 12 month before randomization changes of liver functions with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3 upper limit of normal (ULN) liver disease having impact on survival pregnancy and breast feeding. Women of child bearing potential must agree to the requirements for pregnancy testing and contraceptive methods any contraindications for electric cardioversion (see attachment # 1 for details). any contraindications to cerebral MRI any contraindications to TEE ( perforated viscus; esophageal pathology (stricture, trauma, tumor, scleroderma, Mallory-Weiss tear, diverticulum); tracheoesophageal fistula; active upper GI bleeding; recent upper GI surgery; esophagectomy, esophagogastrectomy.) patients who on the discretion of physician will not benefit from 150 BID dose of dabigatran during study course active hepatitis anemia (hemoglobin level <100g/L) or thrombocytopenia (platelet count <100 × 109/L) alcohol abuse hyperthyroidism

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 74 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
Interventional Model Description: PROBE design, multicenter, active control trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abbreviated course group (ACG)<br>The patients receiving 3-days course of dabigatran etexilate during pre-cardioversion period. After cardioversion has been performed the patients continue with dabigatran etexilate until 30 days after cardioversion | Drug: dabigatran etexilate<br>* 150 mg twice daily (BID)<br>|
| Active Comparator: Conventional course group (CCG)<br>The patients receiving 3-weeks course of dabigatran etexilate before cardioversion of AF. After cardioversion has been performed the patients will continue with dabigatran etexilate until 30 days after cardioversion | Drug: dabigatran etexilate<br>* 150 mg twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of patients with new magnetic resonance imaging (MRI) detected cerebral embolic events | patients with new (not visible at pre-cardioversion MRI) cerebral ischemic lesions revealed at MRI after cardioversion and without a history of acute neurological dysfunction attributable to the lesion or with symptomatic cerebral ischemic stroke after cardioversion confirmed by MRI examination | 30 days after cardioversion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of symptomatic cerebral thromboembolic events (stroke or TIA) | An acute episode of focal or global neurological dysfunction caused by brain, spinal cord or retinal vascular injury as a result of hemorrhage or infarction (with imaging, pathological or other objective evidence of cerebral, spinal cord or retinal injury or clinical evidence with symptoms persisting ≥24 hours or until death and other etiology excluded) or transient (<24 hours) episode of focal neurological dysfunction caused by brain, spinal cord or retinal ischemia without acute infarction | within 30 days after cardioversion | 
| the proportion of patients with major bleeding events after cardioversion | major bleeding as defined by the International Society of Thrombosis and Hemostasis (ISTH) criteria | within 30 days after cardioversion | 
| the proportion of patients with any bleeding events after cardioversion | any clinical obvious bleeding | within 30 days after cardioversion | 
| the proportion of patients with intracranial bleeding events after cardioversion | symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence | within 30 days after cardioversion | 
| the proportion of patients with at least one bleeding event since the first dose of dabigatran | any clinical obvious bleeding | from the first dose of dabigatran etexilate till 30th day after cardioversion | 
| the proportion of patients with at least one major bleeding event since the first dose of dabigatran | major bleeding as defined by the ISTH criteria | from the first dose of dabigatran etexilate till 30th day after cardioversion | 
| the proportion of patients with intracranial bleeding events since the first dose of dabigatran | symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence | from the first dose of dabigatran etexilate till 30th day after cardioversion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, cardioversion, anticoagulation, dabigatran, magnetic resonance imaging