Hydroquinidine Versus Placebo in Patients With Brugada Syndrome (Quidam)

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"

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).

Study Overview

• Status: Terminated
• Conditions: Brugada Syndrome
• Intervention / Treatment: Drug: hydroquinidine; Drug: placebo (sugar)

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80
    • CHU Amiens
  • Angers, France, 49
    • CHU Angers
  • Bordeaux, France, 33
    • CHU Bordeaux
  • Brest, France, 29
    • CHU Brest
  • Grenoble, France, 38
    • CHU Grenoble
  • Lille, France, 59
    • CHRU Lille
  • Lyon, France, 69
    • CHU Lyon
  • Marseille, France, 13
    • AP-HM Marseille
  • Montpellier, France, 34
    • CHU Montpellier
  • Nancy, France, 54
    • CHU Nancy
  • Nantes, France, 44093
    • CHU Nantes
  • Paris, France, 75
    • AP-HP Paris Lariboisière
  • Poitiers, France, 86
    • CHU Poitiers
  • Rennes, France, 35
    • CHU Rennes
  • Strasbourg, France, 67
    • CHU Strasbourg
  • Toulouse, France, 31
    • CHU Toulouse
  • Tours, France, 37
    • CHU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: hydroquinidine; 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; Other Names: Hydroquinidine is commercialized as Serecor
Placebo Comparator: capsules of 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.	Drug: placebo (sugar); capsules of placebo have same design and color than capsules of hydroquinidine except for their content as they contain sugar and not hydroquinidine

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Sanofi
• Investigators: Principal Investigator: V Probst, Pr, CHU NANTES - Hôpital Laënnec; Study Chair: JM Dupuis, Dr, University Hospital, Angers; Study Chair: JS Hermida, Pr, CHU Amiens; Study Chair: M Haissaguerre, Pr, CHU Bordeaux; Study Chair: J Mansourati, Pr, CHU Brest; Study Chair: P Defaye, Dr, University Hospital, Grenoble; Study Chair: S Kacet, Pr, CHRU Lille; Study Chair: P Chevallier, Pr, CHU Lyon; Study Chair: JC Deharo, pr, CHU Marseille; Study Chair: JM Davy, Pr, University Hospital, Montpellier; Study Chair: N Sadoul, Pr, CHU Nancy; Study Chair: A Leenhardt, Pr, CHU PARIS LARIBOISIERE; Study Chair: A Amiel, Dr, CHU Poitiers; Study Chair: P Mabo, Pr, CHU Rennes; Study Chair: M Chauvin, Pr, CHU Strasbourg; Study Chair: D Babuty, Pr, CHU Tours; Study Chair: P Maury, Dr, CHU Toulouse

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 24, 2009
• First Submitted That Met QC Criteria: June 24, 2009
• First Posted (Estimate): June 25, 2009

Study Record Updates

• Last Update Posted (Estimate): November 24, 2014
• Last Update Submitted That Met QC Criteria: November 21, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: ventricular arrhythmia; Brugada; hydroquinidine; patients with Brugada syndrome, high cardiac arrhythmic risk and implanted with an implantable cardioverter defibrillator
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Syndrome; Brugada Syndrome; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Adrenergic alpha-Antagonists; Quinidine; Hydroquinidine
• Other Study ID Numbers: 06/2-D