Clinical trial NCT00927732: Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
Official title: BRD 06/2-D (Quidam) "Evaluation of the Interest of Oral Hydroquinidine Administration to Treat Patients With Brugada Syndrome, High Cardiac Arrhythmic Risk and Implanted With an Implantable Cardioverter Defibrillator"
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Brugada Syndrome
Keywords: Brugada
hydroquinidine
ventricular arrhythmia
patients with Brugada syndrome, high cardiac arrhythmic risk and implanted with an implantable cardioverter defibrillator
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2009-06-25
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: To determine whether hydroquinidine enhances time length before arisen of an appropriate shock registered on the automatic implantable defibrillator (meaning due to ventricular arrhythmia)
timeFrame: 3 years after patient randomization
Secondary outcomes:
measure: To evaluate number and frequency of inappropriate shock with and without hydroquinidine
timeFrame: 3 years after patient randomization
measure: To evaluate the number of tachycardia or of ventricular fibrillations detected by the defibrillator but not having required any treatment
timeFrame: 3 years after patient randomization
measure: To evaluate number of syncope reported by the patient but for which no ventricular arrhythmias has been detected by the defibrillator
timeFrame: 3 years after patient randomization
measure: To evaluate the number and frequency of adverse events appeared under hydroquinidine treatment
timeFrame: 3 years after patient randomization
measure: To evaluate interest of the electrophysiological exploration for determining chances of success of an hydroquinidine
timeFrame: 3 years after patient randomization
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: CHU Brest
city: Grenoble
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: CHU Lyon
city: Marseille
country: France
facility: AP-HM Marseille
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: AP-HP Paris Lariboisière
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: CHU NANTES - Hôpital Laennec
name: V Probst, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Angers
name: JM Dupuis, Dr
role: STUDY_CHAIR
affiliation: CHU AMIENS
name: JS Hermida, Pr
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux
name: M Haissaguerre, Pr
role: STUDY_CHAIR
affiliation: CHU BREST
name: J Mansourati, Pr
role: STUDY_CHAIR
affiliation: University Hospital, Grenoble
name: P Defaye, Dr
role: STUDY_CHAIR
affiliation: CHRU LILLE
name: S Kacet, Pr
role: STUDY_CHAIR
affiliation: Hospices Civils de Lyon
name: P Chevallier, Pr
role: STUDY_CHAIR
affiliation: CHU MARSEILLE
name: JC Deharo, pr
role: STUDY_CHAIR
affiliation: University Hospital, Montpellier
name: JM Davy, Pr
role: STUDY_CHAIR
affiliation: CHU NANCY
name: N Sadoul, Pr
role: STUDY_CHAIR
affiliation: CHU PARIS LARIBOISIERE
name: A Leenhardt, Pr
role: STUDY_CHAIR
affiliation: CHU Poitiers
name: A Amiel, Dr
role: STUDY_CHAIR
affiliation: CHU Rennes
name: P Mabo, Pr
role: STUDY_CHAIR
affiliation: CHU STRASBOURG
name: M Chauvin, Pr
role: STUDY_CHAIR
affiliation: CHU Tours
name: D Babuty, Pr
role: STUDY_CHAIR
affiliation: CHU Toulouse
name: P Maury, Dr
role: STUDY_CHAIR
References: