Comparison of the Efficacy and Safety of Cardioneuroablation to Permanent Pacing in Patients With an Implanted Pacemaker for Symptomatic Bradycardia.
GENTLE-PACE
A Multicenter, Randomized, Double-blind, Research Study comparinG the Efficacy and Safety of cardioneuroablaTion vs Permanent Pacing in Patients With an implantabLE PACEmaker for Symptomatic Bradycardia.
1 other identifier
interventional
99
1 country
2
Brief Summary
Background Sinus node dysfunction (SND) and atrioventricular block (AVB) are significant diagnostic and therapeutic problems. The primary method of their treatment is cardiac pacemaker implantation (PM). Although PM remains the main therapeutic approach for most patients with SND/AVB, long-term PM therapy can be associated with various limitations, complications, and the need for device and electrode replacement. There is increasing evidence for the effectiveness of an alternative approach to functional bradycardia associated with excessive vagal activation - cardioneuroablation (CNA). The method leads to the alleviation or complete resolution of bradycardia symptoms, as well as reflex syncope, providing an opportunity to discontinue PM therapy. Primary aims 1.Evaluation of the efficacy and safety of CNA as a therapy allowing for discontinuation of PM therapy in patients with SND or AVB. Secondary aims
- 1.Evaluation of the efficacy and safety of CNA as a therapy allowing for the optimization of PM therapy in patients with SND and AVB.
- 2.Development of a diagnostic algorithm allowing for the identification of patients with SND and/or AVB suitable for CNA and discontinuation of PM and TLE therapy.
- 3.In addition, blood samples will be collected for future analysis and biobanking.
- 4.Patients up to 50 years old who underwent pacemaker implantation due to sinus node and/or atrioventricular node dysfunction
- 5.Positive response to atropine test
- 6.Age between 18-65 years
- 7.Signed informed consent to participate in the study
- 8.Own heart rate \<30/min
- 9.Fainting after pacemaker therapy initiation
- 10.Persistent and sustained atrial fibrillation
- 11.History of myocarditis
- 12.History of myocardial infarction
- 13.History of cardiac surgery
- 14.History of ablation procedures
- 15.Congenital heart defects
- 16.Congenital atrioventricular block
- 17.Neuromuscular and neurodegenerative diseases
- 18.Indications for expanding the pacemaker system to ICD/CRT-D
- 19.Pregnancy
- 20.Renal insufficiency with GFR \<30 ml/min/1.73m2
- 21.Age below 18 and above 65 years
- 22.HAS-BLED score \>/= 3 points
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Aug 2024
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2023
CompletedFirst Posted
Study publicly available on registry
June 9, 2023
CompletedStudy Start
First participant enrolled
August 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2029
January 3, 2024
December 1, 2023
5 years
May 21, 2023
December 30, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Primary efficacy endpoints- Composite endpoint
Composite endpoint including: * occurrence of non-traumatic loss of consciousness * occurrence of symptoms of presyncope state * determination in the loop recorder recording of events of asymptomatic bradycardia requiring permanent cardiac pacing, understood as: 1. type II degree atrioventricular block and/or 2. atrioventricular block of 2:1 or higher order and/or 3. sinus bradycardia \<40/min during the patient's wakefulness 4. sinus pause \>3 seconds during the patient's wakefulness 5. cardiac pacing despite the PM setting in AAI/VVI mode 30/min after the second intervention.
18 months
Primary safety endpoints- Composite endpoint
Composite endpoint including: * death from any cause * peri-procedural damage to cardiac or vascular structures requiring surgical intervention not resulting in death * ischemic stroke not terminated by death * symptomatic damage to the pulmonary veins * symptomatic injury to the phrenic nerve * de-electrode device-related infective endocarditis * device lodge infection * electrode dysfunction requiring electrode replacement * BARC grade 2, 3 bleeding during postoperative anticoagulant therapy
18 months
Secondary Outcomes (22)
Secondary efficacy endpoint
18 months
Secondary efficacy endpoint
18 months
Secondary efficacy endpoint
18 months
Secondary efficacy endpoint
18 months
Secondary efficacy endpoint
18 months
- +17 more secondary outcomes
Study Arms (3)
Group 1
EXPERIMENTALGroup 1 will undergo EPS, ECVS, CNA with continuation of PM therapy and ILR implantation. Two months later pacing rate, will be assessed. In addition, there will be a non-invasive assessment of the effectiveness of CNA. After another month, EPS and ECVS will be performed and a re-CNA if the ECVS does not show full parasympathetic denervation of the heart. The pacemaker will be set to VVI or AAI 30/min. One month after the second invasive procedure, the pacing rate will be assessed. Patients with zero percentage of PM stimulation will be set to ODO/OVO/OAO-stimulation off mode. Patients will be monitored for the next 12 months. During the next 4 visits repeated every 3 months, patients in this group will undergo non-invasive assessment of the effectiveness of CNA and symptoms of bradycardia. At the 7th visit, patients in this group will be qualified to discontinue of the cardiac pacing treatment, with possible qualification for TLE.
Group 2
EXPERIMENTALGroup 2 will undergo EPS and ECVS with continuation of PM therapy, ILR implantation, without CNA. Two months later pacing rate, will be assessed. After another month, EPS, ECVS and CNA will be made. The pacemaker will be set to VVI or AAI 30/min. One month after the second invasive procedure, patients in this group will have their pacing rate assessed. Patients with zero percentage of PM stimulation will be set to ODO/OVO/OAO-stimulation off mode. Patients will be monitored for the next 12 months. During next 4 visits repeated every 3 months, patients in this group will undergo a non-invasive assessment of the effectiveness of CNA and symptoms of bradycardia. At the 7th visit, the qualification for discontinuation of cardiac pacing treatment will take place, with possible qualification for TLE.
Group 3
ACTIVE COMPARATORGroup 3 patients will only be observed for the duration of the study. The observation period will be 18 months. At subsequent visits 1, 3, 4, 6, 9, 12, 15 months after randomization, they will be assessed for the presence of MAS, paraMAS and assessment of the percentage of stimulation.
Interventions
Invasive electrophysiological study consists in inserting two electrodes into the heart through femoral vein puncture into the right atrium and right ventricle. Then the following measurements are taken: SNRT- sinus rhythm recovery time, cSNRT- corrected sinus rhythm recovery time, Wenckebach point, AH and HV time and HRV-rhythm variability after SNRT measurement. The examination will be performed under general anesthesia.
Extracardiac vagal stimulation consists in leading the electrode through the puncture of the femoral vein, successively to both internal jugular veins and stimulating the vagus nerve at the level of its cranial orifice and lower at the level of the angle of the mandible. Stimulation is performed using the Extra-Cardiac Autonomic NeuroStimulatorPachon. Induction of a sinus pause or AV block during vagal stimulation is considered a positive test result. Absence of sinus pause and AV block during vagal stimulation indicates parasympathetic denervation of the heart. The examination is performed under general anesthesia.
CNA consists in complete parasympathetic denervation of the heart or in its deep neuromodulation by destroying the postganglionic nerve fibers of the vagus nerve, located in the epicardium in the vicinity of the pulmonary veins to the left atrium and in the area of the interatrial septum. It consists in inserting the electrode into the left atrium through puncture of the femoral vein, and then the interatrial septum, and performing ablation in the vicinity of the pulmonary vein orifices and on the interatrial septum at the level of the mitral annulus. Then the electrode is withdrawn into the right atrium and subsequent applications are made in the area of the coronary sinus opening and the roof of the right atrium and the upper part of the interatrial septum. The procedure is performed under general anesthesia. In group 1, CNA will be performed 1 month after randomization. In group 2, CNA will be performed 4 months after randomization.
It consists in re-performing the CNA if full parasympathetic parasympathetic denervation of the heart is not confirmed by ECVS.
Implantation of the implantable loop recorder consists in subcutaneous implantation of the ECG loop recorder in the sternum area.
It consists in evaluating the reliability of the PM system. And the assessment of pacing percentage and recorded arrhythmias. After successful cardioneuroablation in groups 1 and 2, 4 months after randomization, the PM will be programmed to the VVI 30/min mode and after 6 months to the OAO/OVO mode. In group 3 patients and in the case of unsuccessful cardioneuroablation, the pacemaker will be set to the optimal mode for the patient. During the PM control, a non-invasive electrophysiological study (NIEPS) is also performed, in which the SNRT, cSNRT, Wenckebach point and HRV after SNRT measurement are assessed. The procedure will be repeated at subsequent visits 1, 3, 4, 6, 9, 12, 15, 18 months after randomization.
Assessment of arrhythmias recorded in the ILR. The procedure will be repeated at subsequent visits 3, 4, 6, 9, 12, 15, 18 months after randomization.
24 hour ECG recording. The procedure will be repeated at subsequent visits 1, 3, 4, 6, 9, 12, 15, 18 months after randomization.
Medical history assessing symptoms of bradycardia, MAS, paraMAS and complications of performed procedures. The procedure will be repeated at subsequent visits 1, 3, 4, 6, 9, 12, 15, 18 months after randomization.
Eligibility Criteria
You may qualify if:
- Patients who underwent pacemaker implantation before 50 years old due to sinus node and/or atrioventricular node dysfunction
- Positive response to atropine test
- Age between 18-65 years
- Signed informed consent to participate in the study
You may not qualify if:
- Own heart rate \<30/min
- Fainting after pacemaker therapy initiation
- Persistent and sustained atrial fibrillation
- History of myocarditis
- History of myocardial infarction
- History of cardiac surgery
- History of ablation procedures
- Congenital heart defects
- Congenital atrioventricular block
- Neuromuscular and neurodegenerative diseases
- Indications for expanding the pacemaker system to ICD/CRT-D
- Pregnancy
- Renal insufficiency with GFR \<30 ml/min/1.73m2
- Age below 18 and above 65 years
- HAS-BLED score \>/= 3 points
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Mazowiecki Specialist Hospital
Radom, Masovian Voivodeship, 26-617, Poland
Medical University of Silesia
Katowice, Silesian Voivodeship, 40-055, Poland
Related Publications (8)
Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available.
PMID: 34455430RESULTRudbeck-Resdal J, Christiansen MK, Johansen JB, Nielsen JC, Bundgaard H, Jensen HK. Aetiologies and temporal trends of atrioventricular block in young patients: a 20-year nationwide study. Europace. 2019 Nov 1;21(11):1710-1716. doi: 10.1093/europace/euz206.
PMID: 31424500RESULTChung MK, Fagerlin A, Wang PJ, Ajayi TB, Allen LA, Baykaner T, Benjamin EJ, Branda M, Cavanaugh KL, Chen LY, Crossley GH, Delaney RK, Eckhardt LL, Grady KL, Hargraves IG, True Hills M, Kalscheur MM, Kramer DB, Kunneman M, Lampert R, Langford AT, Lewis KB, Lu Y, Mandrola JM, Martinez K, Matlock DD, McCarthy SR, Montori VM, Noseworthy PA, Orland KM, Ozanne E, Passman R, Pundi K, Roden DM, Saarel EV, Schmidt MM, Sears SF, Stacey D, Stafford RS, Steinberg BA, Youn Wass S, Wright JM. Shared Decision Making in Cardiac Electrophysiology Procedures and Arrhythmia Management. Circ Arrhythm Electrophysiol. 2021 Dec;14(12):e007958. doi: 10.1161/CIRCEP.121.007958. Epub 2021 Dec 6.
PMID: 34865518RESULTPachon JC, Pachon EI, Pachon JC, Lobo TJ, Pachon MZ, Vargas RN, Jatene AD. "Cardioneuroablation"--new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005 Jan;7(1):1-13. doi: 10.1016/j.eupc.2004.10.003.
PMID: 15670960RESULTPachon JC, Pachon EI, Cunha Pachon MZ, Lobo TJ, Pachon JC, Santillana TG. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011 Sep;13(9):1231-42. doi: 10.1093/europace/eur163. Epub 2011 Jun 28.
PMID: 21712276RESULTPiotrowski R, Baran J, Sikorska A, Krynski T, Kulakowski P. Cardioneuroablation for Reflex Syncope: Efficacy and Effects on Autonomic Cardiac Regulation-A Prospective Randomized Trial. JACC Clin Electrophysiol. 2023 Jan;9(1):85-95. doi: 10.1016/j.jacep.2022.08.011. Epub 2022 Aug 28.
PMID: 36114133RESULTTulecki L, Polewczyk A, Jachec W, Nowosielecka D, Tomkow K, Stefanczyk P, Kosior J, Duda K, Polewczyk M, Kutarski A. A Study of Major and Minor Complications of 1500 Transvenous Lead Extraction Procedures Performed with Optimal Safety at Two High-Volume Referral Centers. Int J Environ Res Public Health. 2021 Oct 3;18(19):10416. doi: 10.3390/ijerph181910416.
PMID: 34639716RESULTSidhu BS, Gould J, Bunce C, Elliott M, Mehta V, Kennergren C, Butter C, Deharo JC, Kutarski A, Maggioni AP, Auricchio A, Kuck KH, Blomstrom-Lundqvist C, Bongiorni MG, Rinaldi CA; ELECTRa Investigators Group. The effect of centre volume and procedure location on major complications and mortality from transvenous lead extraction: an ESC EHRA EORP European Lead Extraction ConTRolled ELECTRa registry subanalysis. Europace. 2020 Nov 1;22(11):1718-1728. doi: 10.1093/europace/euaa131.
PMID: 32688392RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Przemyslaw Skoczynski, PhD
4th Military Clinical Hospital with Polyclinic, Poland
- STUDY DIRECTOR
Dariusz Jagielski, PhD
4th Military Clinical Hospital with Polyclinic, Poland
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The project is a double-blind study. Blinding will only apply to the study arms with group 1 and 2. Neither the researcher (doctor) nor the participant (patient) will know what invasive procedures will be performed on a given patient. Patients, investigators, and everyone involved in conducting or analyzing the study, along with other persons interested in the results of the study, will remain blinded to the treatment assigned to individual patients (CNA with continuation of PM therapy vs. continuation of PM therapy without CNA) from the beginning of the study until the database is closed. The operator performing EPS, ECVS, CNA and ILR implantation will not be blinded. Operator will not be involved in the subsequent management of the patient in the study.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- MD, PhD
Study Record Dates
First Submitted
May 21, 2023
First Posted
June 9, 2023
Study Start
August 1, 2024
Primary Completion (Estimated)
July 31, 2029
Study Completion (Estimated)
July 31, 2029
Last Updated
January 3, 2024
Record last verified: 2023-12