An interventional study of Invasive electrophysiological study and Extracardiac vagal stimulation in Bradycardia and Syncope, sponsored by 4th Military Clinical Hospital with Polyclinic, Poland. Recruiting at 2 sites in Poland. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-01-03.
Sponsored by 4th Military Clinical Hospital with Polyclinic, Poland · Not applicable, Interventional, and Treatment
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
Methodology
Inclusion criteria
Exclusion criteria
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.
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.
317 studies on the registry are indexed under Bradycardia; 71 are open to participants now.
This study's planned enrollment of 99 is close to the median of 100 across 187 interventional studies indexed under Bradycardia.
Browse Bradycardia studies →4th Military Clinical Hospital with Polyclinic, Poland is the lead sponsor of 10 studies on the registry; 8 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Group 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.
Diagnostic Test: Invasive electrophysiological study · Diagnostic Test: Extracardiac vagal stimulation · Procedure: Cardioneuroablation · Procedure: Redo cardioneuroablation · Procedure: Implantation of the implantable loop recorder · Diagnostic Test: Pacemaker check · Diagnostic Test: Implantable loop recorder check · Diagnostic Test: Holter ECG · Diagnostic Test: Anamnesis
Group 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.
Diagnostic Test: Invasive electrophysiological study · Diagnostic Test: Extracardiac vagal stimulation · Procedure: Cardioneuroablation · Procedure: Implantation of the implantable loop recorder · Diagnostic Test: Pacemaker check · Diagnostic Test: Implantable loop recorder check · Diagnostic Test: Holter ECG · Diagnostic Test: Anamnesis
Group 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.
Diagnostic Test: Pacemaker check · Diagnostic Test: Anamnesis
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.
Also known as: 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.
Also known as: 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.
Also known as: CNA
It consists in re-performing the CNA if full parasympathetic parasympathetic denervation of the heart is not confirmed by ECVS.
Also known as: redo CNA
Implantation of the implantable loop recorder consists in subcutaneous implantation of the ECG loop recorder in the sternum area.
Also known as: 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.
Also known as: 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.
Also known as: 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.
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.
Time frame: 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
Time frame: 18 months
Secondary efficacy endpoint
Occurrence of non-traumatic loss of consciousness
Time frame: 18 months
Secondary efficacy endpoint
Occurrence of syncope in the course of documented bradyarrhythmia
Time frame: 18 months
Secondary efficacy endpoint
Occurrence of symptoms of pre-fainting state
Time frame: 18 months
Secondary efficacy endpoint
Occurrence of presyncope in the course of documented bradyarrhythmia
Time frame: 18 months
Secondary efficacy endpoint
Determination in the loop recorder recording of events of asymptomatic bradycardia requiring permanent pacing of the heart, understood as: 1. atrioventricular block type II 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.
Time frame: 18 months
Secondary efficacy endpoint
Disabling permanent cardiac pacing at visit 3
Time frame: 18 months
Secondary efficacy endpoint
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
Secondary efficacy endpoint
Qualification for removal of PM and TLE system
Time frame: 18 months
Secondary safety endpoint
Death from any cause
Time frame: 18 months
Secondary safety endpoint
Peri-procedural damage to cardiac or vascular structures requiring surgical intervention not resulting in death
Time frame: 18 months
Secondary safety endpoint
Ischemic stroke not terminated by death
Time frame: 18 months
Secondary safety endpoint
Symptomatic pulmonary venous injury
Time frame: 18 months
Secondary safety endpoint
Symptomatic phrenic nerve injury
Time frame: 18 months
Secondary safety endpoint
Asymptomatic phrenic nerve injury
Time frame: 18 months
Secondary safety endpoint
Electrodermal infective endocarditis
Time frame: 18 months
Secondary safety endpoint
PM implantation site infection
Time frame: 18 months
Secondary safety endpoint
Electrode dysfunction
Time frame: 18 months
Secondary safety endpoint
Occurrence of atrial tachyarrhythmias
Time frame: 18 months
Secondary safety endpoint
Development of symptoms of heart failure
Time frame: 18 months
Secondary safety endpoint
Symptoms of inadequate sinus tachycardia
Time frame: 18 months
Secondary safety endpoint
Hospitalization for any reason
Time frame: 18 months
Secondary safety endpoint
BARC grade 2, 3 bleeding during postoperative anticoagulant therapy
Time frame: 18 months
Plan to share: Undecided
Start is estimated for Aug 2024; primary completion for Jul 2029, 59 months later.
Of 47 non-industry interventional studies with no phase under Bradycardia, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 59. This study's planned 59 months is above that.
Counting every sponsor, half of 83 studies reached it within 21 months; a quarter within 12 and three quarters within 38.
How these figures are worked out, and which studies are left out of them.
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4th Military Clinical Hospital with Polyclinic, Poland