Clinical trial NCT03975062: Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study)
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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: atrial fibrillation
cardioversion
anticoagulation
dabigatran
magnetic resonance imaging
Lead sponsor: Ural State Medical University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2019-06-05
Enrollment: 400
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PROBE design, multicenter, active control trial
Primary purpose: PREVENTION

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

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

Primary outcomes:
measure: the proportion of patients with new magnetic resonance imaging (MRI) detected cerebral embolic events
timeFrame: 30 days after cardioversion
Secondary outcomes:
measure: the incidence of symptomatic cerebral thromboembolic events (stroke or TIA)
timeFrame: within 30 days after cardioversion
measure: the proportion of patients with major bleeding events after cardioversion
timeFrame: within 30 days after cardioversion
measure: the proportion of patients with any bleeding events after cardioversion
timeFrame: within 30 days after cardioversion
measure: the proportion of patients with intracranial bleeding events after cardioversion
timeFrame: within 30 days after cardioversion
measure: the proportion of patients with at least one bleeding event since the first dose of dabigatran
timeFrame: from the first dose of dabigatran etexilate till 30th day after cardioversion
measure: the proportion of patients with at least one major bleeding event since the first dose of dabigatran
timeFrame: from the first dose of dabigatran etexilate till 30th day after cardioversion
measure: the proportion of patients with intracranial bleeding events since the first dose of dabigatran
timeFrame: from the first dose of dabigatran etexilate till 30th day after cardioversion
Other outcomes:
measure: rate of sinus rhythm restoration after cardioversion
timeFrame: within 30 days after cardioversion
measure: rate of AF recurrence
timeFrame: from 10 minutes till 30th day after cardioversion
measure: the time until restoration of left atrial (LA) mechanic function
timeFrame: during 5 days from cardioversion until peak A revealed or until atrial fibrillation recurrence (if this happens before)
measure: D-dimer concentration
timeFrame: at the time of cardioversion, 1 day after cardioversion and 10 days after cardioversion
measure: brain natriuretic peptide (BNP) level
timeFrame: right before cardioversion
measure: E/E' ratio
timeFrame: before cardioversion
measure: flow velocity in the left atrial appendage (LAA)
timeFrame: precardioversion day
Locations:
city: Ekaterinburg
country: Russian Federation
facility: Limited Liability Company Medical Association "Novaya Bolnitsa"
Study officials:
affiliation: Ural State Medical University
name: Olga G Smolenskaya, MD
role: STUDY_CHAIR
affiliation: Ural State Medical University
name: Vadim G Grachev, PhD
role: PRINCIPAL_INVESTIGATOR
References: