DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome (DAPREB)
Primary Purpose
Brugada Syndrome
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
3,4-Di-amino-Pyridine
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Brugada Syndrome focused on measuring Brugada syndrome, Electrophysiological study, Ion channel blockade
Eligibility Criteria
Inclusion Criteria:
- Man or woman ≥ 18 years old
- Brugada syndrome diagnosed with a type 1 ECG either spontaneous or drug-induced
- Electrophysiological study indicated for arrhythmic risk stratification purpose
- Inducibility of a sustained ventricular tachycardia (> 30 seconds) or ventricular fibrillation requiring defibrillation
- Physical medical examination
- Signed written informed consent
Exclusion Criteria:
- Personal or familial history of epilepsy
- Pregnancy
- Body weight > 100 kg
- the need of >1 counter shock for defibrillation
- Alcohol or cocaine consumption during the protocol
- Class I (with the exception of local anaesthesia by lidocaine), II, III and IV antiarrhythmic drugs, antidepressant drugs, ATP dependent potassium channel activators, sultopride not stopped for > 7 halve-lives
- No medical insurance
Sites / Locations
- Lariboisière University Hospital - Cardiology department
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
3,4-Di-amino-Pyridine : a single 20 mg dosing
Outcomes
Primary Outcome Measures
Electrophysiological study result (re-inducibility or not) 45 minutes after drug intake
Secondary Outcome Measures
the effect of 3,4-DAP on ST segment elevation in Brugada patients (45 minutes)
the relationship between 3,4-DAP plasma concentration measured at 45 minutes and electrophysiological study result and ST segment elevation
Full Information
NCT ID
NCT00701077
First Posted
June 18, 2008
Last Updated
December 3, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT00701077
Brief Title
DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
Acronym
DAPREB
Official Title
DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
recruitments issues
Study Start Date
September 12, 2008 (Actual)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
April 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The Brugada syndrome is a rare disease potentially leading to severe arrhythmic events in otherwise healthy subjects.In many patients an Implantable cardiovertor defibrillator (ICD) is implanted to prevent sudden cardiac death. ICD are however associated with potential complications and are not available in all countries.Pharmacological blockade of specific ion channels (Ito) represents a promising therapeutic approach in this syndrome.The 3,4-diaminopyridine (3,4-DAP) is a pharmacological Ito blocker that can be used in humans.The aim of the study is to evaluate the effect of 3,4-DAP on ventricular arrhythmia inducibility in Brugada patients requiring an electrophysiological study for arrhythmic risk stratification.
Detailed Description
Background:
The Brugada syndrome is a rare disease potentially leading to severe arrhythmic events in otherwise healthy subjects.In many patients an Implantable cardiovertor defibrillator (ICD) is implanted to prevent sudden cardiac death. ICD are however associated with potential complications and are not available in all countries.Pharmacological blockade of specific ion channels (Ito) represents a promising therapeutic approach in this syndrome. Experimental data show that increased Ito current may be associated with both the ECG feature and arrhythmogenic substrate observed in the syndrome. Moreover, Ito blockade reverse the ECG abnormalities and suppress arrhythmogenicity.The 3,4-diaminopyridine (3,4-DAP) is a pharmacological Ito blocker that is already used in humans for another indication.
Main objective:
The aim of the study is to evaluate the effect of 3,4-DAP on ventricular arrhythmia inducibility in Brugada patients requiring an electrophysiological study for arrhythmic risk stratification.
First end point:
Re-inducibility or non re-inducibility of sustained ventricular arrhythmia during electrophysiological study on treatment
Tested hypothesis:
The 3,4-DAP decreases the proportion of re-inducibility during the electrophysiological study with a re-inducibility rate of 80% in the placebo group and 25% in the 3,4-DAP group
Secondary objective:
to assess the effect of 3,4-DAP on ST segment elevation in Brugada patients
to describe the relationship between 3,4-DAP plasma concentration measured at 45 minutes and electrophysiological study result and ST segment elevation
Study design:
2 centres, randomised, double blind, parallel groups, placebo controlledA single dose of 20 mg of 3,4-DAP
Included patients and number of patients:
Included patients will all have a diagnosed Brugada type 1 ECG and will require an electrophysiological study for arrhythmic risk stratification purpose. Only inducible patients will be included in the study.Using a classical approach, the hypothesis would be that 80% of on placebo patients would be re-inducible when only 25% of on drug patients would. To test such an hypothesis, 32 patients (16 in each group) would have been necessary (a=5%, b=20%).Provided the essential binary response of the electrophysiological study we choose a sequential approach in order to get the opportunity stop for success or futility the inclusions before the end of the study. The maximum number of included patients will then be 42 (21 in each group).
Protocol duration:
Study duration is 48 hours for each patient.The protocol duration is planned for 5 years.
Per protocol procedures:
Electrophysiological study with ventricular programmed stimulation performed twice
Continuous ECG recording- Blood sampling for 3,4-DAP plasma concentration measurement Potential implications:If the study hypotheses are confirmed it would then be justified to design long term efficacy studies in Brugada patients implanted with an ICD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brugada Syndrome
Keywords
Brugada syndrome, Electrophysiological study, Ion channel blockade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
3,4-Di-amino-Pyridine : a single 20 mg dosing
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
3,4-Di-amino-Pyridine
Intervention Description
a single 20 mg dosing
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Electrophysiological study result (re-inducibility or not) 45 minutes after drug intake
Time Frame
45 minutes after drug intake
Secondary Outcome Measure Information:
Title
the effect of 3,4-DAP on ST segment elevation in Brugada patients (45 minutes)
Time Frame
at 45 minutes
Title
the relationship between 3,4-DAP plasma concentration measured at 45 minutes and electrophysiological study result and ST segment elevation
Time Frame
at 45 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Man or woman ≥ 18 years old
Brugada syndrome diagnosed with a type 1 ECG either spontaneous or drug-induced
Electrophysiological study indicated for arrhythmic risk stratification purpose
Inducibility of a sustained ventricular tachycardia (> 30 seconds) or ventricular fibrillation requiring defibrillation
Physical medical examination
Signed written informed consent
Exclusion Criteria:
Personal or familial history of epilepsy
Pregnancy
Body weight > 100 kg
the need of >1 counter shock for defibrillation
Alcohol or cocaine consumption during the protocol
Class I (with the exception of local anaesthesia by lidocaine), II, III and IV antiarrhythmic drugs, antidepressant drugs, ATP dependent potassium channel activators, sultopride not stopped for > 7 halve-lives
No medical insurance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabrice EXTRAMIANA, MD, PhD
Organizational Affiliation
Lariboisière University Hospital - Cardiology Department
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lariboisière University Hospital - Cardiology department
City
Paris
ZIP/Postal Code
75010
Country
France
12. IPD Sharing Statement
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DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
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