Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT00701077 |
| Other study ID # |
P060802 |
| Secondary ID |
EUDRACT 2007-004 |
| Status |
Terminated |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 12, 2008 |
| Est. completion date |
April 2010 |
Study information
| Verified date |
December 2020 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
