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

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ClinicalTrials.gov Identifier: NCT03975062
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Vadim Grachev, Ural Medical University

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: dabigatran etexilate Phase 4

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: PROBE design, multicenter, active control trial
Masking: Single (Outcomes Assessor)
Masking Description: Blinded evaluation of primary outcome by Imaging expert, who will made decision regarding achievement of primary outcome
Primary Purpose: Prevention
Official Title: "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
Actual Study Start Date : December 28, 2017
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2020


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)




Primary Outcome Measures :
  1. the proportion of patients with new magnetic resonance imaging (MRI) detected cerebral embolic events [ Time Frame: 30 days after cardioversion ]
    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


Secondary Outcome Measures :
  1. the incidence of symptomatic cerebral thromboembolic events (stroke or TIA) [ Time Frame: within 30 days after cardioversion ]
    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

  2. the proportion of patients with major bleeding events after cardioversion [ Time Frame: within 30 days after cardioversion ]
    major bleeding as defined by the International Society of Thrombosis and Hemostasis (ISTH) criteria

  3. the proportion of patients with any bleeding events after cardioversion [ Time Frame: within 30 days after cardioversion ]
    any clinical obvious bleeding

  4. the proportion of patients with intracranial bleeding events after cardioversion [ Time Frame: within 30 days after cardioversion ]
    symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence

  5. the proportion of patients with at least one bleeding event since the first dose of dabigatran [ Time Frame: from the first dose of dabigatran etexilate till 30th day after cardioversion ]
    any clinical obvious bleeding

  6. the proportion of patients with at least one major bleeding event since the first dose of dabigatran [ Time Frame: from the first dose of dabigatran etexilate till 30th day after cardioversion ]
    major bleeding as defined by the ISTH criteria

  7. the proportion of patients with intracranial bleeding events since the first dose of dabigatran [ Time Frame: from the first dose of dabigatran etexilate till 30th day after cardioversion ]
    symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence


Other Outcome Measures:
  1. rate of sinus rhythm restoration after cardioversion [ Time Frame: within 30 days after cardioversion ]
    achieving and maintaining of sinus rhythm for at least 10 min after shock

  2. rate of AF recurrence [ Time Frame: from 10 minutes till 30th day after cardioversion ]
    recurrent episodes of AF or atrial flutter

  3. the time until restoration of left atrial (LA) mechanic function [ Time Frame: during 5 days from cardioversion until peak A revealed or until atrial fibrillation recurrence (if this happens before) ]
    transmitral flow peak A restoration on results of echocardiography

  4. D-dimer concentration [ Time Frame: at the time of cardioversion, 1 day after cardioversion and 10 days after cardioversion ]
    D-dimer concentration in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site

  5. brain natriuretic peptide (BNP) level [ Time Frame: right before cardioversion ]
    BNP level in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site

  6. E/E' ratio [ Time Frame: before cardioversion ]
    the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity on results of echocardiography

  7. flow velocity in the left atrial appendage (LAA) [ Time Frame: precardioversion day ]
    flow velocity in the LAA TEE evaluation



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Ages Eligible for Study:   19 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975062


Contacts
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Contact: Vadim G Grachev, PhD +79193920247 ext +79193920247 grach_vad@mail.ru

Locations
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Russian Federation
Limited Liability Company Medical Association "Novaya Bolnitsa" Recruiting
Ekaterinburg, Russian Federation, 620109
Contact: Elena G Fokina    +79122474898    fokina@newhospital.ru   
Sponsors and Collaborators
Ural Medical University
Boehringer Ingelheim
Investigators
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Study Chair: Olga G Smolenskaya, MD Ural Medical University
Principal Investigator: Vadim G Grachev, PhD Ural Medical University

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Responsible Party: Vadim Grachev, Principal Investigator, Ural Medical University
ClinicalTrials.gov Identifier: NCT03975062     History of Changes
Other Study ID Numbers: 1160.242
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vadim Grachev, Ural Medical University:
atrial fibrillation
cardioversion
anticoagulation
dabigatran
magnetic resonance imaging
Additional relevant MeSH terms:
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Dabigatran
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants