NCT Number: NCT05896592
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.
Methodology
Inclusion criteria
1. Patients up to 50 years old who underwent pacemaker implantation due to sinus node and/or atrioventricular node dysfunction 2. Positive response to atropine test 3. Age between 18-65 years 4. Signed informed consent to participate in the study
Exclusion criteria
1. Own heart rate <30/min 2. Fainting after pacemaker therapy initiation 3. Persistent and sustained atrial fibrillation 4. History of myocarditis 5. History of myocardial infarction 6. History of cardiac surgery 7. History of ablation procedures 8. Congenital heart defects 9. Congenital atrioventricular block 10. Neuromuscular and neurodegenerative diseases 11. Indications for expanding the pacemaker system to ICD/CRT-D 12. Pregnancy 13. Renal insufficiency with GFR <30 ml/min/1.73m2 14. Age below 18 and above 65 years 15. HAS-BLED score >/= 3 points
Randomization, study scheme Qualified patients will be randomly assigned (1:1:1) to group 1 undergoing first-stage invasive electrophysiology study (EPS), extracardiac vagus nerve stimulation (ECVS) and CNA with continued PM therapy and implantable loop recorder (ILR) implantation, to group 2 undergoing first-stage EPS and ECVS with continued PM therapy, ILR implantation, and no CNA, and to group 3 where patients will undergo observation only for the entire study. The follow-up time will be 18 months. Groups 1 and 2 will be blinded. Two months after the first invasive procedure, the secondary endpoint-stimulation rate in all groups will be assessed. In addition, a non-invasive evaluation of the efficacy of CNA and the incidence of syncope (MAS) and collapse (paraMAS) will take place in group 1, as well as an evaluation of the pacing percentage. After another month during the second hospitalization, the following will be performed: EPS and ECVS, and repeat CNA if ECVS does not show full parasympathetic cardiac denervation. In group 2, after 2 months, non-invasive tests will also be performed to assess and presence of MAS, paraMAS symptoms, and to assess pacing rates. After another month, during the second hospitalization, the following will be performed: EPS, ECVS and CNA. Group 1 and 2 patients will have their pacemaker set to VVI/AAI 30/min. Group 3 patients will then be evaluated for pacing rates and MAS, paraMAS symptoms. At the third visit, one month after the second invasive procedure in group 1 and 2 patients, the pacing percentage will be assessed. Patients with zero pacing percentage PM will be put on ODO/OVO/OAO-pacing off mode. Patients with a pacing percentage greater than zero PM will be set to their optimal mode. A pacing percentage of <0.1% will be treated as 0%, which will be confirmed in the ILR control. For the next 12 months, patients will be observed. During this period, at the next 4 visits repeated every 3 months, groups 1 and 2 will undergo a non-invasive assessment of CNA efficacy and bradycardia symptoms, while group 3 will be evaluated for MAS, paraMAS and pacing percentage assessment. At the 7th visit, the qualification of patients in groups 1 and 2 for discontinuation of continued pacing treatment will take place, with possible qualification for TLE.
Justification Early and late results of a new strategy which is CNA, indicate the possibility of developing an new approach that allows patients with functional bradycardia to decide whether to discontinue or optimize PM therapy. However, standardized approaches based on noninvasive and invasive techniques have not yet been validated and evaluated in a prospective, multicenter, randomized, controlled trial with long-term remote follow-up, including ILR.
Interested in participating?
Request Info18 year–65 year
All sexes
Interventional
Not applicable
Mazowiecki Specialist Hospital, Radom, Masovian Voivodeship, Poland
Visit 1- Screening, recruitment, randomization.
Hospitalization 1-1 month from randomization Group 1- EPS, ECVS, CNA, ILR implantation Group 2- EPS, ECVS, ILR implantation Group 3- observation
Visit 2-3 months after randomization
Group 1 and 2:
Group 3 observation:
Hospitalization 2-4 months from randomization Group 1 - EPS, ECVS, redo CNA if required Group 2 - EPS, ECVS, CNA Group 1 and 2 patients will have their pacemaker set to VVI/AAI 30/min. For patients of Groups 1 and 2 in whom the CNA proved to be ineffective, the PM will be programmed in the optimal mode for them.
Visit 3-6 months after randomization
Group 1 and 2:
Group 3 observation:
Visits 4, 5, 6 - consecutively 9, 12, 15 months after randomization
Groups 1 and 2:
During these visits, patients in Group 3 and Groups 1 and 2 who had their pacing restored/optimized will be interviewed for possible MAS and paraMAS symptoms, perform a physical examination, and check the PM with assessment of pacing percentage and pacing mode optimization.
Visit 7 - ending the study - 18 months from randomization.
Group 1 and 2:
During this visit, Group 3 and Group 1 and 2 patients with previously pacing restored/optimized will be interviewed for possible MAS and paraMAS symptoms, perform a physical examination and PM check with assessment of pacing percentage and pacing mode optimisation.
The ILR will be left in place until the battery runs out or will be removed sooner at the patient's request.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Other names: EPS
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.
Other names: ECVS
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.
Other names: CNA
It consists in re-performing the CNA if full parasympathetic parasympathetic denervation of the heart is not confirmed by ECVS.
Other names: redo CNA
Implantation of the implantable loop recorder consists in subcutaneous implantation of the ECG loop recorder in the sternum area.
Other names: ILR implantation
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.
Other names: PM check
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.
Other names: ILR check
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.
Time frame: 18 months
Composite endpoint including:
Time frame: 18 months
Composite endpoint including:
Time frame: 18 months
Occurrence of non-traumatic loss of consciousness
Time frame: 18 months
Occurrence of syncope in the course of documented bradyarrhythmia
Time frame: 18 months
Occurrence of symptoms of pre-fainting state
Time frame: 18 months
Occurrence of presyncope in the course of documented bradyarrhythmia
Time frame: 18 months
Determination in the loop recorder recording of events of asymptomatic bradycardia requiring permanent pacing of the heart, understood as:
Time frame: 18 months
Disabling permanent cardiac pacing at visit 3
Time frame: 18 months
Demonstration of a statistically significant lower pacing rate in the group of patients undergoing CNA vs patients who continued PM therapy without CAN
Time frame: 18 months
Qualification for removal of PM and TLE system
Time frame: 18 months
Death from any cause
Time frame: 18 months
Peri-procedural damage to cardiac or vascular structures requiring surgical intervention not resulting in death
Time frame: 18 months
Ischemic stroke not terminated by death
Time frame: 18 months
Symptomatic pulmonary venous injury
Time frame: 18 months
Symptomatic phrenic nerve injury
Time frame: 18 months
Asymptomatic phrenic nerve injury
Time frame: 18 months
Electrodermal infective endocarditis
Time frame: 18 months
PM implantation site infection
Time frame: 18 months
Electrode dysfunction
Time frame: 18 months
Occurrence of atrial tachyarrhythmias
Time frame: 18 months
Development of symptoms of heart failure
Time frame: 18 months
Symptoms of inadequate sinus tachycardia
Time frame: 18 months
Hospitalization for any reason
Time frame: 18 months
BARC grade 2, 3 bleeding during postoperative anticoagulant therapy
Contact information is provided by the study sponsor or research team.
Bruno Hrymniak, MD
CONTACT
Przemyslaw Skoczynski, PhD
CONTACT
4th Military Clinical Hospital with Polyclinic, Poland
Other
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.
Acronym: GENTLE-PACE
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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