Efficacy of a Right-sided Ablation of the Anterior Ganglionated Plexus for Neurally Mediated Syncope

NCT04755101 | Recruiting DMC

• 1 other identifier: B3222020000229
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

The third study on CardNM (CardNMH3 study) is a multicenter, double-blind, randomized trial with a sham control group investigating the efficacy and safety of a computed tomography (CT)-guided, right-sided ablation of the anterior ganglionated plexus to prevent recurrence of syncope in patients with neurally mediated syncope (NMS). The primary goal of the study is to determine whether a CT-guided, right-sided ablation of the anterior ganglionated plexus safely reduces the risk of recurrent episodes of syncope in patients with a history of recurrent NMS. Two-third of the patients will be randomized to the active arm and one-third to the control arm (sham). The study procedure is described in the 'detailed description' and 'intervention description'. Syncope burden, syncope occurrence and quality of life will be assessed by questionnaires at baseline and at 1, 3, 6 and 12 months. A 24-h rhythm registration will be performed at baseline and at 1-, 3- and 6-month follow-up to investigate the influence of the intervention on heart rate. The effect of CardNM on blood pressure and on chronotropic sinus node function will be evaluated in 2 additional substudies. Patients enrolled in the blood-pressure substudy will undergo a 24-h blood pressure monitoring at baseline and at 1, 3 and 6 months. Participants in the sinus node competence substudy will undergo a bicycle exercise test at baseline and at 1, 3 and 6 months. Investigators aim to achieve complete follow-up for 110 patients who meet the study enrollment criteria. If syncope-free survival (primary endpoint) is significantly different between the 2 arms after the enrollment of fewer than 110 patients (minimum 55 patients), enrollment into the trial will be prematurely stopped. The study may also be terminated prematurely if safety concerns occur.

Conditions

Syncope, Neurogenic; Syncope

Keywords

cardioneuroablation; cardio-neuromodulation; ganglionated plexi; right-anterior ganglionated plexus; ablation

Outcome Measures

Primary Outcomes (1)

• Syncope free survival

  The primary efficacy endpoint is the number of days elapsed from study procedure to first syncope recurrence or to study close-out.

  From date of randomization until the date of first syncope recurrence, assessed up to 12-month follow-up.

Secondary Outcomes (4)

• Syncope burden

  1-, 3-, 6- and 12-month follow-up.

• Number of beats with prespecified P-P intervals

  1-, 3- and 6-month follow-up.

• Heart rate variability

  1-, 3- and 6-month follow-up.

• Quality of life scale based on the questionnaire 'Impact of Syncope on Quality of Life (ISQL)

  1-, 3-, 6- and 12-month follow-up.

Study Arms (2)

Righ-sided ARGP ablation

ACTIVE COMPARATOR

two-thirds of the patients will be randomized to procedural arm A: a diagnostic evaluation followed by cardio-neuromodulation (CardNM) and a pharmacological evaluation

Procedure: EPS, electro-anatomical mapping, ARGP ablation, and pharmacological evaluation.

Placebo

SHAM COMPARATOR

one-third of the patients will be randomized to procedural arm B: a diagnostic evaluation followed by a pharmacological evaluation.

Procedure: EPS, electro-anatomical mapping, and pharmacological evaluation.

Interventions

EPS, electro-anatomical mapping, ARGP ablation, and pharmacological evaluation. PROCEDURE

EPS and electro-anatomical mapping of the right atrium and the surrounding veins. A target line (TL) is traced at the posteroseptal side of the junction, between the right atrium and superior vena cava, facing the mid and caudal parts of the right superior pulmonary vein antrum on the right heart cavities on a CT image imported into the CARTO system. This map will be carefully merged with the CT image and the TL will be visible. Sequential ablations will be delivered along theTL until the procedure endpoint is reached. Pharmacological evaluation.

Righ-sided ARGP ablation

EPS, electro-anatomical mapping, and pharmacological evaluation. PROCEDURE

EPS and electro-anatomical mapping of the right atrium and the surrounding veins. A target line (TL) is traced at the posteroseptal side of the junction, between the right atrium and superior vena cava, facing the mid and caudal parts of the right superior pulmonary vein antrum on the right heart cavities on a CT image imported into the CARTO system. This map will be carefully merged with the CT image and the TL will be visible. No ablation is performed (sham). Pharmacological evaluation.

Also known as: EPS, electro-anatomical mapping, no ablation, and pharmacological evaluation.

Placebo

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be in sinus rhythm and have ≥3 syncopes during the last 18 months\* and a previous positive tilt table test (TTT) with a cardioinhibitory or mixed response (VASIS I, IIA or IIB classification).
• \* syncopes occurring during TTT are not taken into account
• Patients have a 'preserved cholinergic SN reserve', defined as ≥20% sinus heart rate increment during a pharmacological test with atropine.

You may not qualify if:

• \<14 years age
• Any unstable medical condition, life expectancy \<12 months
• Inability to provide consent or undergo follow-up
• Syncope due to a non-cardiac disease or due to an advanced neuropathy
• Moderate to severe valvular or subvalvular aortic stenosis or mitral stenosis
• Overt heart failure or left ventricular ejection fraction \<45%
• Current pregnancy
• Chronotropic negative medications unless judged mandatory
• g amiodarone intake during the 2 months preceding enrollment
• Alternating RBBB and LBBB, HV interval \>70 ms
• LBBB, bifascicular block (RBBB + LAHB, RBBB + LPHB)
• PR interval permanently \>240 ms
• Pacemaker or automated implantable cardioverter defibrillator device
• Permanent AF, PAF or electrical cardioversion during the last 6 months
• Channelopathy

Sponsors & Collaborators

• Imelda Hospital, Bonheiden: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator
• AZ Sint-Jan AV: collaborator
• Biosense Webster, Inc.: collaborator
• Trium Clinical Consulting: collaborator

Study Sites (3)

Imeldaziekenhuis

Bonheiden, 2820, Belgium

RECRUITING

Algemeen Ziekenhuis Sint Jan

Bruges, 8000, Belgium

NOT YET RECRUITING

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Syncope, Vasovagal; Syncope

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Philippe Debruyne, MD

  Imeldaziekenhuis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe Debruyne, MD

CONTACT

0032478229896; philippe.debruyne@skynet.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist, head of Electrophysiology and Research Departments

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 15, 2021
• Study Start: March 24, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3)