Ablation in Brugada Syndrome for the Prevention of VF (BRAVE)

Ablation in Brugada Syndrome for Prevention of VF - A Randomized, Multi-center Study of Epicardial Ablation in Brugada Syndrome Patients to Prevent Arrhythmia Recurrence

This trial aims to develop evidence based curative treatment with optimal net benefit for patients with Brugada syndrome.

Study Overview

• Status: Completed
• Conditions: Brugada Syndrome
• Intervention / Treatment: Procedure: Catheter Ablation

Detailed Description

This trial aims to develop evidence based curative treatment with optimal net benefit for patients with Brugada syndrome. Since a recent non-randomized pilot study and scarce case reports documented potential clinical benefit of epicardial ablation of fragmented electrograms in the region of the right ventricular outflow tract, patients in this trial will be randomized to continued implanted cardioverter defibrillator therapy (control arm) or ablation of areas of fragmented electrograms in the right ventricular outflow tract plus continued implanted cardioverter defibrillator therapy (intervention arm). A projected 92 patients in each group will be studied.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center, University of Amsterdam
• Thailand
  • Bangkok, Thailand
    • Ramathibodi Hospital
  • Bangkok, Thailand
    • Chulalongkorn University
  • Bangkok, Thailand
    • Bhumipol Adulyadej Hospital, Royal Thai Air Force
  • Bangkok, Thailand
    • Pacific Rim Electrophysiology Research Institute Data Coordinating Center
  • Chiang Mai, Thailand
    • Chiang Mai University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The diagnosis of Brugada syndrome is based on 2013 HRS/EHRA/APHRS Consensus document criteria
• Diagnosed symptomatic BrS with an implanted ICD within the last 5 years
• Diagnosed symptomatic BrS with an implanted ICD longer than 5 years but has at least 1 appropriate shock within the last 5 years
• The patient is legally competent, willing and able to undergo the study and signed the informed consent
• The patient is willing and able to adhere to the follow-up visit protocol

Exclusion Criteria:

• A patient who does not meet inclusion criteria
• A patient who has had a previous epicardial ablation
• A patient who is pregnant (which would exclude an ablation procedure)
• A patient with a co-morbid condition that possesses undue risk of general anesthesia or epicardial ablation
• A patient who has a history of radiation therapy on the thorax

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; Control arm - continued implanted cardioverter defibrillator therapy
Active Comparator: Intervention Arm; ablation of areas of fragmented signal in the right ventricular outflow tract plus continued implanted cardioverter defibrillator therapy	Procedure: Catheter Ablation; catheter ablation of fragmented signal in the right ventricular outflow tract
Other: Single Cross Over Arm; these patients were initially assigned to the control arm of the study. When these patients met the primary outcome of the study it is allowed for these patients to be included in the intervention arm and/or to start quinidine	Procedure: Catheter Ablation; catheter ablation of fragmented signal in the right ventricular outflow tract

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom of Ventricular Fibrillation/Tachycardia Recurrences	Survival from ventricular fibrillation of shocked ventricular arrhythmias causing ICD discharge	3 year followup

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom without drug	Freedom of shocked ventricular arrhythmias without the use of anti-arrhythmic drugs during 3 years of follow-up	3 years

Collaborators and Investigators

• Sponsor: Pacific Rim Electrophysiology Research Institute
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Koonlawee Nademanee, MD, Pacific Rim Electrophysiology Research Institute

Publications and helpful links

General Publications

• Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal AC, Christiansen M, Tan HL, Wilde AA, Nogami A, Sheppard MN, Veerakul G, Behr ER. Fibrosis, Connexin-43, and Conduction Abnormalities in the Brugada Syndrome. J Am Coll Cardiol. 2015 Nov 3;66(18):1976-1986. doi: 10.1016/j.jacc.2015.08.862.
• Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation. 2011 Mar 29;123(12):1270-9. doi: 10.1161/CIRCULATIONAHA.110.972612. Epub 2011 Mar 14.
• Ten Sande JN, Coronel R, Conrath CE, Driessen AH, de Groot JR, Tan HL, Nademanee K, Wilde AA, de Bakker JM, van Dessel PF. ST-Segment Elevation and Fractionated Electrograms in Brugada Syndrome Patients Arise From the Same Structurally Abnormal Subepicardial RVOT Area but Have a Different Mechanism. Circ Arrhythm Electrophysiol. 2015 Dec;8(6):1382-92. doi: 10.1161/CIRCEP.115.003366. Epub 2015 Oct 19.
• Wilde AA, Nademanee K. Epicardial Substrate Ablation in Brugada Syndrome: Time for a Randomized Trial! Circ Arrhythm Electrophysiol. 2015 Dec;8(6):1306-8. doi: 10.1161/CIRCEP.115.003500. No abstract available.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): November 13, 2024
• Study Completion (Actual): November 13, 2024

Study Registration Dates

• First Submitted: February 18, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimated): March 10, 2016

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Ventricular arrhythmias; cardiac death; aborted cardiac arrest
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Genetic Diseases, Inborn; Disease; Arrhythmias, Cardiac; Brugada Syndrome; Syndrome
• Other Study ID Numbers: PacificRERI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Medical journals, abstract submissions and results database