E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with syndroma of Brugada who have an automatic implantable cardiac defibrillator |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059027 |
E.1.2 | Term | Brugada syndrome |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to compare for patients with Brugada syndrome having an Implantable Automatic Defibrillator (IAD) the time length before the happening of an appropriate electric shock registered on the IAD when they are under hydroquinidine treatment or when they are under placebo (double-blinded cross-over study design) |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives: - To evaluate the number and frequency of inappropriate shocks with or without hydroquinidine treatment - - To evaluate the number of tachycardia or of ventricular fibrillations detected by the defibrillator but not having required a treatment - To evaluate the number of syncopes encountered by the patient for which no rhythm trouble was recorded on the defibrillator - To evaluate the number and frequency of indesirable adverse events occurring during treatment with hydroquinidine - To evaluate the interest of the electrophysiological exploration to determine the chances of success of a treatment with hydroquinidine - To analyse the delay of occurrence of a rhythm trouble with or without hydroquinidine treatment in relation to the patient genetic status (mutation or not on the SCN5A gene)
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Criteria for inclusion: Patients aged 18 or > 18, presenting a type I Brugada syndrome, having an Implantable Automatic Defibrillator (IAD) and being either symptomatic [ previous occurrence of cardiac arrest or ventricular fibrillation reduced by the IAD, OR previous occurrence of syncope suggesting cardiac rhythm trouble] or either asymptomatic, all patients being affiliated to social security, having given their written informed consent, having no known allergy to hydroquinidine. Criteria for randomization : - Those above listed - For patients with asymptomatic Brugada syndrome: positive electrophysiological exploration at the visit of inclusion - Absence of hypersensitivity reaction after intake of one capsule of hydroquinidine - No relevant abnormality in the electrocardiogram after 3 to 5 days of hydroquinidine treatment - No relevant abnormality in blood formula The study will allow the randomization of: - 60 patients with symptomatic type I Brugada syndrome having presented a cardiac arrest or a ventricular fibrillation reduced by the IAD - 70 patients symptomatic type I Brugada syndrome who have presented a syncope suggesting cardiac rhythm trouble - 70 patients asymptomatic but with spontaneous type I electrocardiogram and for which the electrophysiological exploration induced a severe rhythm trouble
|
|
E.4 | Principal exclusion criteria |
Criteria of non inclusion : - Patients not presenting the inclusion criteria - Pregnancy or lactation - Female of procreating age without contraceptive methods - contra-indications to the use of hydroquinidine (ex: intolerance to fructose, myasthenia,…) Criteria for non randomization : - Those above listed - Patient with asymptomatic Brugada syndrome presenting a negative electrophysiological exploration at the visit of inclusion - Hypersensitivity reaction after intake of one capsule of hydroquinidine - Relevant abnormality in the electrocardiogram after 3 to 5 days of hydroquinidine treatment - Relevant abnormality in blood formula
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of an appropriate electric shock registered on the implantable automatic defibrillator will led to: - to change of treatment arm if the patient was in the first phase of treatment - - study drop out if the patient was in the second phase of treatment
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |