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出境医 / 临床实验 / Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study) (RE-SOUND)
Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study) (RE-SOUND)
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
| 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
Study Design
| 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 |
Arms and Interventions
| 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)
|
Outcome Measures
Primary Outcome Measures :
- 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 :
- 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
- 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
- the proportion of patients with any bleeding events after cardioversion [ Time Frame: within 30 days after cardioversion ]any clinical obvious bleeding
- 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
- 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
- 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
- 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:
- 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
- rate of AF recurrence [ Time Frame: from 10 minutes till 30th day after cardioversion ]recurrent episodes of AF or atrial flutter
- 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
- 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
- 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
- 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
- flow velocity in the left atrial appendage (LAA) [ Time Frame: precardioversion day ]flow velocity in the LAA TEE evaluation
Eligibility Criteria
| 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
Contacts and Locations
Contacts
| Contact: Vadim G Grachev, PhD | +79193920247 ext +79193920247 | grach_vad@mail.ru |
Locations
| 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 State Medical University
Boehringer Ingelheim
Investigators
| Study Chair: | Olga G Smolenskaya, MD | Ural State Medical University | |
| Principal Investigator: | Vadim G Grachev, PhD | Ural State Medical University |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 28, 2019 | ||||||
| First Posted Date ICMJE | June 5, 2019 | ||||||
| Last Update Posted Date | June 5, 2019 | ||||||
| Actual Study Start Date ICMJE | December 28, 2017 | ||||||
| Estimated Primary Completion Date | December 30, 2020 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
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
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | No Changes Posted | ||||||
| Current Secondary Outcome Measures ICMJE |
|
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||
| Current Other Pre-specified Outcome Measures |
|
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| Original Other Pre-specified Outcome Measures | Same as current | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | Evaluation of Abbreviated Versus Conventional Course of Dabigatran Etexilate Before Electric Cardioversion in Patients With Atrial Fibrillation (RE-SOUND Study) | ||||||
| Official Title ICMJE | "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 | ||||||
| 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 |
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| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 4 | ||||||
| Study Design ICMJE | 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
|
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| Condition ICMJE | Atrial Fibrillation | ||||||
| Intervention ICMJE | Drug: dabigatran etexilate
150 mg twice daily (BID)
|
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||
| Recruitment Status ICMJE | Unknown status | ||||||
| Estimated Enrollment ICMJE |
400 | ||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||
| Estimated Study Completion Date ICMJE | December 30, 2020 | ||||||
| Estimated Primary Completion Date | December 30, 2020 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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| Sex/Gender ICMJE |
|
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| Ages ICMJE | 19 Years to 74 Years (Adult, Older Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
| Listed Location Countries ICMJE | Russian Federation | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03975062 | ||||||
| Other Study ID Numbers ICMJE | 1160.242 | ||||||
| Has Data Monitoring Committee | No | ||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Vadim Grachev, Ural State Medical University | ||||||
| Study Sponsor ICMJE | Ural State Medical University | ||||||
| Collaborators ICMJE | Boehringer Ingelheim | ||||||
| Investigators ICMJE |
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| PRS Account | Ural State Medical University | ||||||
| Verification Date | June 2019 | ||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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