Back to resultsEvaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study) (RE-SOUND)
Primary Purpose
Atrial Fibrillation
Status
Unknown status
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
dabigatran etexilate
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation focused on measuring atrial fibrillation, cardioversion, anticoagulation, dabigatran, magnetic resonance imaging
Eligibility 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
Sites / Locations
- Limited Liability Company Medical Association "Novaya Bolnitsa"Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Abbreviated course group (ACG)
Conventional course group (CCG)
Arm Description
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
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
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
the proportion of patients with major bleeding events after cardioversion
major bleeding as defined by the International Society of Thrombosis and Hemostasis (ISTH) criteria
the proportion of patients with any bleeding events after cardioversion
any clinical obvious bleeding
the proportion of patients with intracranial bleeding events after cardioversion
symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence
the proportion of patients with at least one bleeding event since the first dose of dabigatran
any clinical obvious bleeding
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
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
Full Information
NCT ID
NCT03975062
First Posted
May 28, 2019
Last Updated
June 2, 2019
Sponsor
Ural State Medical University
Collaborators
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT03975062
Brief Title
Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study)
Acronym
RE-SOUND
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 28, 2017 (Actual)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
December 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ural State Medical University
Collaborators
Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
atrial fibrillation, cardioversion, anticoagulation, dabigatran, magnetic resonance imaging
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
PROBE design, multicenter, active control trial
Masking
Outcomes Assessor
Masking Description
Blinded evaluation of primary outcome by Imaging expert, who will made decision regarding achievement of primary outcome
Allocation
Randomized
Enrollment
400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Abbreviated course group (ACG)
Arm Type
Experimental
Arm Description
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
Arm Title
Conventional course group (CCG)
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
dabigatran etexilate
Intervention Description
150 mg twice daily (BID)
Primary Outcome Measure Information:
Title
the proportion of patients with new magnetic resonance imaging (MRI) detected cerebral embolic events
Description
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
Time Frame
30 days after cardioversion
Secondary Outcome Measure Information:
Title
the incidence of symptomatic cerebral thromboembolic events (stroke or TIA)
Description
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
Time Frame
within 30 days after cardioversion
Title
the proportion of patients with major bleeding events after cardioversion
Description
major bleeding as defined by the International Society of Thrombosis and Hemostasis (ISTH) criteria
Time Frame
within 30 days after cardioversion
Title
the proportion of patients with any bleeding events after cardioversion
Description
any clinical obvious bleeding
Time Frame
within 30 days after cardioversion
Title
the proportion of patients with intracranial bleeding events after cardioversion
Description
symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence
Time Frame
within 30 days after cardioversion
Title
the proportion of patients with at least one bleeding event since the first dose of dabigatran
Description
any clinical obvious bleeding
Time Frame
from the first dose of dabigatran etexilate till 30th day after cardioversion
Title
the proportion of patients with at least one major bleeding event since the first dose of dabigatran
Description
major bleeding as defined by the ISTH criteria
Time Frame
from the first dose of dabigatran etexilate till 30th day after cardioversion
Title
the proportion of patients with intracranial bleeding events since the first dose of dabigatran
Description
symptomatic intraparenchymal, intraventricular, subarachnoid, subdural, epidural hemorrhage with imaging or pathological evidence
Time Frame
from the first dose of dabigatran etexilate till 30th day after cardioversion
Other Pre-specified Outcome Measures:
Title
rate of sinus rhythm restoration after cardioversion
Description
achieving and maintaining of sinus rhythm for at least 10 min after shock
Time Frame
within 30 days after cardioversion
Title
rate of AF recurrence
Description
recurrent episodes of AF or atrial flutter
Time Frame
from 10 minutes till 30th day after cardioversion
Title
the time until restoration of left atrial (LA) mechanic function
Description
transmitral flow peak A restoration on results of echocardiography
Time Frame
during 5 days from cardioversion until peak A revealed or until atrial fibrillation recurrence (if this happens before)
Title
D-dimer concentration
Description
D-dimer concentration in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site
Time Frame
at the time of cardioversion, 1 day after cardioversion and 10 days after cardioversion
Title
brain natriuretic peptide (BNP) level
Description
BNP level in laboratory evaluation in sub-set of 100 patients only at one pre-selected investigational site
Time Frame
right before cardioversion
Title
E/E' ratio
Description
the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity on results of echocardiography
Time Frame
before cardioversion
Title
flow velocity in the left atrial appendage (LAA)
Description
flow velocity in the LAA TEE evaluation
Time Frame
precardioversion day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vadim G Grachev, PhD
Phone
+79193920247
Ext
+79193920247
Email
grach_vad@mail.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olga G Smolenskaya, MD
Organizational Affiliation
Ural State Medical University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Vadim G Grachev, PhD
Organizational Affiliation
Ural State Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Limited Liability Company Medical Association "Novaya Bolnitsa"
City
Ekaterinburg
ZIP/Postal Code
620109
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena G Fokina
Phone
+79122474898
Email
fokina@newhospital.ru
12. IPD Sharing Statement
Plan to Share IPD
No
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Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study)
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