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

"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

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

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: dabigatran etexilate

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
    • Recruiting
    • Limited Liability Company Medical Association "Novaya Bolnitsa"
    • Contact: Elena G Fokina; Phone Number: +79122474898; Email: fokina@newhospital.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abbreviated course group (ACG); 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; 150 mg twice daily (BID)
Active Comparator: Conventional course group (CCG); 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; 150 mg twice daily (BID)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of sinus rhythm restoration after cardioversion	achieving and maintaining of sinus rhythm for at least 10 min after shock	within 30 days after cardioversion
rate of AF recurrence	recurrent episodes of AF or atrial flutter	from 10 minutes till 30th day after cardioversion
the time until restoration of left atrial (LA) mechanic function	transmitral flow peak A restoration on results of echocardiography	during 5 days from cardioversion until peak A revealed or until atrial fibrillation recurrence (if this happens before)
D-dimer concentration	D-dimer concentration in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site	at the time of cardioversion, 1 day after cardioversion and 10 days after cardioversion
brain natriuretic peptide (BNP) level	BNP level in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site	right before cardioversion
E/E' ratio	the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity on results of echocardiography	before cardioversion
flow velocity in the left atrial appendage (LAA)	flow velocity in the LAA TEE evaluation	precardioversion day

Collaborators and Investigators

• Sponsor: Ural State Medical University
• Collaborators: Boehringer Ingelheim
• Investigators: Study Chair: Olga G Smolenskaya, MD, Ural State Medical University; Principal Investigator: Vadim G Grachev, PhD, Ural State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2017
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: June 2, 2019
• First Posted (Actual): June 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 2, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; atrial fibrillation; anticoagulation; cardioversion; dabigatran
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No