Invasive and Clinical Features in Patients With Brugada Syndrome Undergoing Catheter Ablation

Invasive and Clinical Features in Patients With Brugada Syndrome Undergoing Catheter Ablation: a Prospective, Single-centre, Randomized, Sham-controlled, and Masked Pilot Study

This clinical trial aims to learn about the electrophysiological and clinical effects of radiofrequency catheter ablation in patients with Brugada syndrome. The main questions it seeks to answer are:

• What are the immediate effects of catheter radiofrequency ablation in cardiac electrophysiology?
• What is the relation between invasive and clinical features in patients with Brugada syndrome undergoing ablation? Researchers will compare ablation and control groups to see if there is a difference in clinical and invasive markers of the disease in one year of follow-up.

Study Overview

• Status: Recruiting
• Conditions: Brugada Syndrome
• Intervention / Treatment: Device: Radiofrequency catheter ablation; Device: Sham procedure

Detailed Description

Brugada syndrome (BS) is an electric cardiac disorder characterized by a typical electrocardiographic pattern and an increased risk of cardiac arrhythmias and sudden death. Most arrhythmic events occur during rest, fever or under circumstances of increased vagal activity. In the last decade, catheter ablation has emerged as a valuable and potentially curative therapy for patients with BS. However, little is known about its mechanisms or long-term effects on clinical and invasive markers. This prospective, single-centre, randomized, sham-controlled, and masked pilot study will investigate the impact of catheter ablation in 20 patients with Brugada syndrome, who will be randomized to ablation or control group, with a 1:1 allocation ratio and clinically followed for 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-000
    • Recruiting
    • Instituto do Coração - InCor - HC/FMUSP
    • Contact: Mauricio Ibrahim Scanavacca, MD; PhD; Phone Number: +551126615312; Email: mauricio.scanavacca@incor.usp.br
    • Contact: Mirella Esmanhotto Facin, MD; Phone Number: +5511970272217; Email: mirellafacin@gmail.com
    • Sub-Investigator: Cristiano Pisani, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a type 1 Brugada ECG pattern, as characterized by ST-segment elevation (≥2mm) with upward concavity associated with T-wave inversion, in at least one of the right precordial leads, positioned at the second, third or fourth intercostal space, either spontaneously or induced by a provocative test with Class I anti-arrhythmic drugs according to Vaughan Williams
• Patients clinically stable for at least six months before the enrollment
• Able to cope with follow-up visits up to one year after the intervention
• Patients who have signed the written informed consent

Exclusion Criteria:

• Pregnant women
• Patients with structural heart disease
• Patients with a known cardiac or systemic autonomic disorder
• Patients with a history of previous right ventricular outflow tract ablation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ablation; Radiofrequency catheter ablation of the abnormal - prolonged and fragmented - electrophysiologic substrate of Brugada syndrome	Device: Radiofrequency catheter ablation; Radiofrequency application via catheter to burn the electroanatomic substrate implicated in Brugada syndrome
Sham Comparator: Control; Femoral venous punctions, catheter insertion, programmed electrical stimulation and electroanatomic mapping, with a similar duration to the ablation procedure	Device: Sham procedure; Venous and epicardial punctions, catheter insertions, programmed electrical stimulation and electroanatomical mapping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area of abnormal potentials	Electroanatomic duration map	first 30 minutes after the intervention
Induction of sustained ventricular arrhythmias by programmed electrical stimulation	Programmed electrical stimulation (PES) performed on two sites (right ventricular apex and right ventricular outflow tract, unless the patient had inducible ventricular tachycardia at the first location), with energy of twice the diastolic threshold, using two drive cycles (S1: 600 and 430 ms) up to 3 extra stimuli (S2 to S4) with 200 ms as the shortest coupling time. The PVS result is considered positive if sustained ventricular fibrillation or polymorphic ventricular tachycardia is induced.	first 30 minutes after the intervention
Maximum potential duration	Maximum length of ventricular signs on bipolar electrogram	first 30 minutes after the intervention
Local activation time	Measured by unipolar catheters placed in the epicardial and endocardial ventricular surfaces	first 30 minutes after the intervention
Activation recovery interval	Surrogate marker of the action potential duration, measured by unipolar catheters placed in the epicardial and endocardial ventricular surfaces	first 30 minutes after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous type 1 Brugada electrocardiographic pattern in standard12 lead and superior leads electrocardiogram	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces.	up to one year after the procedure
Spontaneous type 1 Brugada electrocardiographic pattern in 12 lead 24 hour Holter monitoring	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces during 12 lead 24h Holter ECG Monitoring	up to one year after the procedure
Spontaneous type 1 Brugada electrocardiographic pattern during treadmill test	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces, during treadmill test.	up to one year after the procedure
Occurrence of life threatening arrhythmic events	Occurrence of at least one of the following: arrhythmic syncope, documented sustained ventricular tachycardia or ventricular fibrillation, sudden cardiac death or appropriate implantable cardiac defibrillator therapy	up to one year after the procedure

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Biosense Webster, Inc.

Publications and helpful links

General Publications

• Pappone C, Brugada J, Vicedomini G, Ciconte G, Manguso F, Saviano M, Vitale R, Cuko A, Giannelli L, Calovic Z, Conti M, Pozzi P, Natalizia A, Crisa S, Borrelli V, Brugada R, Sarquella-Brugada G, Guazzi M, Frigiola A, Menicanti L, Santinelli V. Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome. Circ Arrhythm Electrophysiol. 2017 May;10(5):e005053. doi: 10.1161/CIRCEP.117.005053.
• Patocskai B, Yoon N, Antzelevitch C. Mechanisms Underlying Epicardial Radiofrequency Ablation to Suppress Arrhythmogenesis in Experimental Models of Brugada Syndrome. JACC Clin Electrophysiol. 2017 Apr;3(4):353-363. doi: 10.1016/j.jacep.2016.10.011. Epub 2016 Dec 21.
• Kotake Y, Barua S, Kazi S, Virk S, Bhaskaran A, Campbell T, Bennett RG, Kumar S. Efficacy and safety of catheter ablation for Brugada syndrome: an updated systematic review. Clin Res Cardiol. 2022 Apr 22. doi: 10.1007/s00392-022-02020-3. Online ahead of print. Erratum In: Clin Res Cardiol. 2022 Jun 2;:

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Estimate): January 13, 2023

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Radiofrequency catheter ablation; Brugada syndrome; Electroanatomic mapping; Invasive electrophysiological study
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Syndrome; Brugada Syndrome
• Other Study ID Numbers: IIS-470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data sharing will be provided under proper request to the principal investigator
• IPD Sharing Time Frame: After the article's publication
• IPD Sharing Access Criteria: Under request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes