Empiric Quinidine for Asymptomatic Brugada Syndrome

A Prospective Trial Of Empiric Quinidine Therapy For Asymptomatic Brugada Syndrome.

The purpose of this study is to determine if quinidine therapy (not guided by the results of electrophysiologic studies) will reduce the long-term risk of arrhythmic events in asymptomatic Brugada Syndrome.

Study Overview

• Status: Withdrawn
• Conditions: Arrhythmia
• Intervention / Treatment: Drug: quinidine; Drug: no therapy

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany
    • University Medical Centre Mannheim
• Israel
  • Tel Aviv, Israel, 64239
    • Tel Aviv Medical Center
• Italy
  • Pavia, Italy
    • University of Pavia and IRCCS Fondazione Policlinico San Matteo
• Japan
  • Osaka, Japan
    • National Cardiovascular Center
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Centre
• United States
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Institute for Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Asymptomatic Brugada syndrome.

   • "Brugada syndrome" is defined as the presence of a Type-I Brugada electrocardiogram [coved ST-segment elevation ≥2 mm (0.2 mV) in V1, V2 or V3] either spontaneously (at rest, in the baseline state or during a febrile episode) or following a standard drug-challenge test (with flecainide, ajmaline, procainamide, or pilsicainide) and recorded either with standard electrode position or with the precordial electrodes placed on the second or third intercostal space. Negative T waves in the precordial leads are not required to define a Type I electrocardiogram.
   • "Asymptomatic patients" will be defined as patients without a history of cardiac arrest, a history of "arrhythmic syncope" or a history of "suspected arrhythmic syncope." Arrhythmic syncope" is a syncope occurring during documented ventricular tachyarrhythmias. "Suspected arrhythmic syncope" is syncope without documented arrhythmias believed to be caused by a tachyarrhythmia based on clinical judgment. In other words, patients with typical vagal syncope will be counted as "asymptomatic" and will be accepted to the registry whereas patients with a clinical history suggesting "syncope other than vagal syncope" will not be accepted to this Registry.
   • Genetic confirmation (identification of a disease-causing mutation) will not be required for establishing the diagnosis of Brugada syndrome but will be recorded when present.

2. Patients with Questionable Brugada Syndrome who are asymptomatic.

   • Patients with "Questionable Brugada Syndrome" are defined as patients with type II or III electrocardiogram who have an inconclusive result during a drug challenge with a sodium channel blocker. "Asymptomatic" is defined as above.
   • Genetic testing will not be required. However, patients with "Questionable Brugada" based on electrocardiographic criteria will be defined as "Patients with Brugada Syndrome" if a disease-causing mutation is identified.

Exclusion Criteria:

1. A history of cardiac arrest, "arrhythmic syncope" or "suspected arrhythmic syncope" (as defined above).
2. Evidence of organic heart disease. The evaluation considered mandatory for excluding heart disease will consist of electrocardiogram, echocardiogram and exercise stress testing. Additional tests will be performed only if clinically indicated.
3. Evidence of non-cardiac disease likely to affect 5-year survival.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quinidine; Patients with type I Brugada electrocardiogram (either spontaneous or following a drug challenge with sodium channel blocker) who never experienced arrhythmia-related symptoms. Patients will receive quinidine therapy at the discretion of the attending physician.	Drug: quinidine; quinidine at highest tolerated dose. Expected doses are hydroquinidine 600 - 900 mg daily.; Other Names: Serecor; Quiniduran
Active Comparator: no therapy; Patients with asymptomatic Brugada syndrome who opted to receive no therapy following the recommendation of their attending physician	Drug: quinidine; quinidine at highest tolerated dose. Expected doses are hydroquinidine 600 - 900 mg daily.; Other Names: Serecor; Quiniduran; Drug: no therapy; No therapy; this is not a placebo-controlled trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Combined endpoint of all cause mortality and spontaneous life-threatening arrhythmias.	Long term (>5 years)

Collaborators and Investigators

• Sponsor: International Registry of Asymptomatic Brugada Syndrome
• Investigators: Principal Investigator: Sami Viskin, M.D., Tel Aviv Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): February 1, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: November 8, 2008
• First Submitted That Met QC Criteria: November 10, 2008
• First Posted (Estimate): November 11, 2008

Study Record Updates

• Last Update Posted (Actual): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Brugada syndrome; quinidine; Asymptomatic Brugada Syndrome
• 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; 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
• Other Study ID Numbers: 1297368; No grants at this point