Epicardial Ablation in Brugada Syndrome. An Extension Study of 500 BrS.Patients

Epicardial Ablation in 500 Consecutive Brugada Syndrome Patients

This study represents an extension of a previous study (NCT02641431) on the acute and long-term benefit of epicardial ablation on elimination of both BrS-ECG pattern and VT/VF inducibility in 500 consecutive BrS patients.

Study Overview

• Status: Recruiting
• Conditions: ECG Brugada Pattern
• Intervention / Treatment: Procedure: Ablation

Detailed Description

According to previous protocol (NCT02641431), 300 additional consecutive selected patients having an ICD implantation will be enrolled up to a total of 500 BrS patients. Echocardiography with cardiac deformation analysis, three-dimensional color-coded voltage, activation and duration electroanatomical maps before and after ajmaline (1mg/kg in 5 minutes) wiil determine the site and the size of the arrhythmogenic substrate as characterized by abnormally prolonged fragmented ventricular potentials and potential wall motion abnormalities. Primary endpoint will be identification and elimination of this electrophysiological substrate by RF applications leading to ECG pattern normalization and VT/VF non-inducibility before and after ajmaline. Patients will be followed up to 10 years after ablation by sequential 12-lead ECG and Holter recording, Echocardiography, ICD interrogation, VT/VF inducibility patterns before and after ajmaline test.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlo Pappone, MD; Phone Number: +39 02 52774260; Email: carlo.pappone@af-ablation.org

Study Locations

• Italy
  • Milano
    • San Donato Milanese, Milano, Italy, 20097
      • Recruiting
      • IRCCS Policlinico S. Donato
      • Contact: Carlo Pappone, MD, PhD; Phone Number: 00390252774260; Email: carlo.pappone@af-ablation.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptomatic BrS patients with typical BrS-related symptoms (cardiac arrest or syncope) or without typical BrS-related symptoms (dizziness, palpitations, presyncope, dyspnea) ICD implantation, spontaneous or ajmaline-induced type 1 Br pattern.

Exclusion Criteria:

• Age < 18 years, prior epicardial ablation, pregnancy, co-morbidities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ablation; Radiofrequency epicardial ablation	Procedure: Ablation; Epicardial Radiofrequency ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type 1 BrS-ECG pattern elimination by epicardial ablation before and after ajmaline test.	Normalization of ECG pattern after elimination by radio-frequency ablation of all abnormal epicardial potentials	1 day after ablation
VT/VF inducibility	Programmed stimulation was achieved at twice the diastolic threshold and randomly performed at RV apex and RV outflow tract using up to 3 drive cycle lengths (from 600 to 350ms) and up to three extrastimuli (S2-S4) delivered from the apex and outflow tract of the right ventricle.	immediately after mapping and ablation
Absence of VT/VF	Absence of VT/VF by ICD interrogation	1,3,6,12,18,24,36,48,60,72,84,96,108,120 months after ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absence of Br Pattern and RV mechanical abnormalities using echo and cardiac deformation analysis before and after ajmaline test	Abolition of typical BrS-ECG pattern and RV mechanical abnormalities before and after ajmaline.	3 months
Absence of VA episodes at EP study	Non-inducibility of VT/VT at programmed electrophysiological study	3 months
Absence of Br Pattern at ajmaline test	Normalization of 12-lead ECG recording and echo parameters at baseline and after ajmaline test	6 months
Absence of VA episodes	ICD interrogation	6 months
Absence of VA episodes	ICD interrogation and ajmaline test	12 months
Absence of Br Pattern at ajmaline test	Normalization of 12-lead ECG recording and echo parameters at baseline and after ajmaline test	12 months
Absence of Br Pattern at ajmaline test	Normalization of 12-lead ECG recording at baseline and after ajmaline test	18 months
Absence of VA episodes	ICD interrogation	24 months
Absence of Br ECG pattern after ajmaline test	Normalization of 12-lead ECG recording at baseline and after ajmaline test	24 months
Absence of VA episodes at EP study	ICD interrogation	36 months
Absence of Br Pattern at ajmaline test	Normalization of 12-lead ECG recording at baseline and after ajmaline test	36 months
Absence of Br Pattern at ajmaline test	Normalization of 12-lead ECG recording at baseline and after ajmaline test	48 months
Absence of VA episodes at EP study	ICD interrogation	48 months up to 120 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato
• Investigators: Principal Investigator: Carlo Pappone, MD, IRCCS Policlinico San Donato, Milan

Publications and helpful links

General Publications

• Ciconte G, Santinelli V, Vicedomini G, Borrelli V, Monasky MM, Micaglio E, Giannelli L, Negro G, Giordano F, Mecarocci V, Mazza BC, Locati E, Anastasia L, Calovic Z, Pappone C. Non-invasive assessment of the arrhythmogenic substrate in Brugada syndrome using signal-averaged electrocardiogram: clinical implications from a prospective clinical trial. Europace. 2019 Dec 1;21(12):1900-1910. doi: 10.1093/europace/euz295.
• Pappone C, Ciconte G, Manguso F, Vicedomini G, Mecarocci V, Conti M, Giannelli L, Pozzi P, Borrelli V, Menicanti L, Calovic Z, Della Ratta G, Brugada J, Santinelli V. Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome. J Am Coll Cardiol. 2018 Apr 17;71(15):1631-1646. doi: 10.1016/j.jacc.2018.02.022.
• Ciconte G, Santinelli V, Brugada J, Vicedomini G, Conti M, Monasky MM, Borrelli V, Castracane W, Aloisio T, Giannelli L, Di Dedda U, Pozzi P, Ranucci M, Pappone C. General Anesthesia Attenuates Brugada Syndrome Phenotype Expression: Clinical Implications From a Prospective Clinical Trial. JACC Clin Electrophysiol. 2018 Apr;4(4):518-530. doi: 10.1016/j.jacep.2017.11.013. Epub 2018 Feb 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Estimated): September 28, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (Actual): April 10, 2017

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Brugada Syndrome
• Other Study ID Numbers: IRCCSDonato

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No