Brugada Syndrome
Conditions
Keywords
Brugada, hydroquinidine, ventricular arrhythmia, patients with Brugada syndrome, high cardiac arrhythmic risk and implanted with an implantable cardioverter defibrillator
Brief summary
The specific aim of this study is to determine whether hydroquinidine administration can prevent heart from appearance of ventricular arrhythmia detected by the automatic implantable defibrillator (ICD).
Detailed description
During this double-blind randomized cross-over study, patient will receive during 18 months treatment 1 (hydroquinidine or placebo) and, after 7 days of wash-out, patient will receive treatment 2 (meaning for example hydroquinidine if treatment 1 was placebo). Time length before arisen of an appropriate shock registered on the defibrillator (meaning due to ventricular arrhythmia) will be assessed during treatment 1 period and treatment 2 period.We hypothesized that hydroquinidine administration will enhance time length before arisen of an appropriate shock and thus mean that hydroquinidine administration can prevent heart from appearance of ventricular arrhythmia. Patient's defibrillator recordings will be analysed every 6 months plus when patient experiences an ICD shock. If the shock delivered by the ICD is appropriate and happens during treatment 1 period, patient will switch to treatment 2 period after 7 days of wash-out. If the shock delivered by the ICD is appropriate and happens during treatment 2 period, study will be finished for this patient.Before starting the study, each patient will test which dose of hydroquinidine she/he requires to have an hydroquinidine concentration in her/his blood included between 3 and 6 µmol/L. Planned enrollment: 200 subjects (60 being symptomatic with histories of aborted sudden cardiac death or of ventricular fibrillation, 70 being symptomatic with histories of syncope considered as of arrhythmic origin, 70 being asymptomatic with a spontaneous type 1 ECG and a positive electrophysiological exploration)
Interventions
DRUGhydroquinidine
capsules of 300 mg LP, 1 or 2 or 3 times per day : frequency will be determined by tests after patient inclusion before her/his randomization
DRUGplacebo (sugar)
capsules of placebo have same design and color than capsules of hydroquinidine except for their content as they contain sugar and not hydroquinidine
Sponsors
Sanofi
Nantes University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy adult (at least 18 years of age) * Informed consent form signed * Subject affiliated to French health insurance (Sécurité Sociale) * Type 1 Brugada syndrome either symptomatic or asymptomatic * Not pregnant, taking oral contraceptive measure if able to procreate * If patient with asymptomatic type 1 Brugada, electrophysiological exploration must be positive at study inclusion * No current intake of betablocking medicine used in cardiac insufficiency (bisoprolol, carvedilol, metoprolol) * No current myasthenia * No current treatment with halofantrine, pentamidine, moxifloxacin * No current treatment with some neuroleptics * Known hypersensitivity to hydroquinidine * Intolerance to fructose, syndrome of glucose or galactose malabsorption, deficit in sucrase isomaltase- Cardiac insufficiency * Histories of torsades de pointe * Intake of medicine giving torsades de pointe
Exclusion criteria
* Subject not fulfilling inclusion criteria * Subject being before study entry under hydroquinidine treatment but either at a dose \> 3 capsules per day or at a dose of 1, 2 or 3 capsules per day but with a plasmatic hydroquinidine concentration \>6µmol/L or \<3 µmol/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine whether hydroquinidine enhances time length before arisen of an appropriate shock registered on the automatic implantable defibrillator (meaning due to ventricular arrhythmia) | 3 years after patient randomization |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate number and frequency of inappropriate shock with and without hydroquinidine | 3 years after patient randomization |
| To evaluate the number of tachycardia or of ventricular fibrillations detected by the defibrillator but not having required any treatment | 3 years after patient randomization |
| To evaluate number of syncope reported by the patient but for which no ventricular arrhythmias has been detected by the defibrillator | 3 years after patient randomization |
| To evaluate the number and frequency of adverse events appeared under hydroquinidine treatment | 3 years after patient randomization |
| To evaluate interest of the electrophysiological exploration for determining chances of success of an hydroquinidine | 3 years after patient randomization |
Countries
France
Outcome results
None listed