Hydroquinidine Versus Placebo in Patients With Brugada Syndrome

Phase 3

Terminated

• Conditions: Brugada Syndrome
• Interventions: Drug: hydroquinidine; Drug: placebo (sugar)

• Registration Number: NCT00927732
• Lead Sponsor: Nantes University Hospital

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)

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-06-24
• Study First Submitted QC: 2009-06-24
• Study First Posted: 2009-06-25
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2014-11
• Last Update Submitted: 2014-11-21
• Last Update Posted: 2014-11-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
hydroquinidine	hydroquinidine	As it is a cross-over study, patient will taken treatment 1 for 18 months (ex: hydroquinidine) and then treatment 2 (placebo in this case) for 18 months.
capsules of sugar	placebo (sugar)	As it is a cross-over study, patient will taken treatment 1 for 18 months (ex: hydroquinidine) and then treatment 2 (placebo in this case) for 18 months.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (17)

CHU Amiens; 🇫🇷 Amiens, France

CHRU Lille; 🇫🇷 Lille, France

CHU Nantes; 🇫🇷 Nantes, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

CHU Lyon; 🇫🇷 Lyon, France

CHU Toulouse; 🇫🇷 Toulouse, France

CHU Tours; 🇫🇷 Tours, France

CHU Angers; 🇫🇷 Angers, France

CHU Bordeaux; 🇫🇷 Bordeaux, France

CHU Brest; 🇫🇷 Brest, France

CHU Grenoble; 🇫🇷 Grenoble, France

CHU Montpellier; 🇫🇷 Montpellier, France

CHU Nancy; 🇫🇷 Nancy, France

AP-HM Marseille; 🇫🇷 Marseille, France

AP-HP Paris Lariboisière; 🇫🇷 Paris, France

CHU Rennes; 🇫🇷 Rennes, France

CHU Poitiers; 🇫🇷 Poitiers, France