Pacemaker Implantation Versus Cardioneuroablation for Functional Atrioventricular Block

NCT ID: NCT05774262

Last Updated: 2024-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-01

Study Completion Date

2026-12-31

Brief Summary

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The TELE-SPACER study is a multicenter, noncommercial, physician-initiated, proof-of-concept, prospective, randomized, controlled, unblinded clinical trial and registry designed to compare two methods of treatment of patients with functional Atrio-Ventricular Block (AVB): the guidelines-recommended elective pacemaker (PM) therapy vs cardiovascular autonomic tests (CAT), electrophysiologic assessment (EPS) with referral to cardioneuroablation (CNA) and reevaluation of indications for PM therapy.

The main questions TELE-SPACER aims to answer are:

* Can the investigators successfully treat functional AVB without implantable device (PM)?
* Can the investigators prove the feasibility and safety and demonstrate non-inferiority of CNA procedure in patients with functional AVB, avoiding long-term permanent pacing, its limitations, complications and costs ?

The TELE-SPACER trial will validate the European Society of Cardiology (ESC) recommendations (level C of evidence: expert opinion) for elective PM implantation and will introduce CNA as effective treatment in the functional AVB patient population.

Functional AVB - defined as a persistent or paroxysmal AVB with a positive results of atropine test

Detailed Description

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TELE-SPACER trial will enroll a minimum of 100 participants, males and females, 18-75 years old: 1) with indications for elective PM implantation due to atrioventricular block (AVB) according to 2021 ESC guidelines on cardiac pacing; 2) who had positive atropine tests. Participants will be randomized into two groups - either optimized guideline-recommended PM therapy (group A, n=50) or reevaluation for PM therapy after CAT/EPS and experimental procedure CNA (group B, n=50). Participants who will choose to opt-out of randomization will be included in the registry (group C) and will undergo patient-tailored intervention through shared decision-making with a possibility of either PM implantation, CNA or observation only. The registry is expected to include up to 200 participants.

Patient enrollment time is anticipated to last 2 years. Recruitment will take place in four study sites, in two distinct phases. First, the investigators will identify potential participants with AVB and a positive atropine test, confirming significant dependence of heart rhythm and conduction on the vagus nerve (hyperactivity of vagus nerve). Their medical records will be analyzed by the Scientific Committee (symptoms evaluation, physical examination, documentation of AVB). In the second phase eligible participants will be invited by the investigator to participate in the trial during medical consultation. After explanations describing the study protocol, including the risk and benefits, they will sign the written informed consent to participate in the study or will choose to opt-out of randomization to be included in the registry only (group C). Informed consent will be obtained only if it is clear that the patient truly understands the nature of the study. Alternatively, the patient will be encouraged to take a copy of the consent form home to contemplate enrolment in the study. Only participants who voluntarily consent will be included. Participants will be able to withdraw at any time without compromising their medical care.

Paricipants will be randomized in 1:1 allocation to either group A or group B. Randomization will be performed centrally and assigned automatically to each patient via internet. The randomization list will be blocked per center, with randomly varying block sizes of 2 and 4. The centers will not be aware of the block sizes. The PM implantation and treatment allocation will not be blinded to the patient or follow-up physician. Participants in either arm of the study will be followed-up at regular intervals for a minimum of 12 months. During the 12-month study duration, the use of effective contraception will be recommended for women of child-bearing age.

The period of the screening and randomization visit will last from 0 to 7 days, and the qualification for elective PM implantation (group A) or elective loop recorder monitoring/CAT/EPS (group B) and subsequent therapeutic decisions (CNA, DDDR, other treatment based on the test result) from 0 to 4 weeks. Parameter analysis baseline, including ECG telemonitoring, QOL and symptoms, will take place at randomization (0 months), 3, 6 and 12 months. Participants will be assessed using cardiovascular autonomic testing (CAT) with telemedical registration at 6 and 12 months. All measured parameters, as well as demographic and clinical data will be recorded in the study database.

Participants in group A (PM, n = 50) will receive care on the basis of the 2021 ESC Guidelines on Cardiac Pacing Recommendations. They will be implanted with PM (DDD pacemaker or its modification as HBP/LBBAP - His-Purkinje or left bundle branch area pacing) and will be monitored with external ECG recorder (certified medical devices of at least class IIa) with telemonitoring. Group B participants (CNA, n = 50) will be implanted with implantable loop recorder (ILR) device (Biotronik, Biomonitor 3m), also with remote tele-monitoring, with the same thresholds for automatic episode recording. As part of telemonitoring system, all participants will receive in the period before the procedure a dedicated telemonitoring kit consisting of a portable ECG device and a tablet with a sim card for network connection. This telemonitoring kit will enable regular self-testing, symptom reporting and interactive, objective telemedicine consultations. Participants will be provided with 24/7 contact with medical staff in the telemonitoring center specialized in cardiac arrhythmias and implantable device monitoring. The major reason for ECG recording is to provide ECG documentation of clinical AVB, as well as monitoring of participants before and after CNA (or PM implantation, if accepted). In case of severe AVB, the emergency system will always be called.

Participants in group B will be referred for EPS and ECVS (extracardiac vagal nerve stimulation) with the possibility of simultaneous CNA after exclusion of advanced and occult distal AVBs. Once the effectiveness of the CNA is confirmed, the patient will be further monitored. If CNA is not succesful and/or its immediate effectiveness is not confirmed (meeting the ESC criteria for pacemaker implantation after CNA), the patient will be referred for pacemaker implantation and will cross-over into group A.

CNA will be performed in group B under general anesthesia by experienced operators (at least 25 CNA procedures preformed). After EPS, a biatral, binodal, anatomically guided CNA will be performed under ECVS guidance, with a demonstration of the vagal reflex (complete asystole or AVB with atrial pacing) at the onset of the CNA and its complete disappearance after a successful CNA. Additional ablation substrates will also be allowed and performed.

Participants included in the registry (group C) will undergo an individually tailored intervention through shared decision making (SDM) with the option of implantation of PM (subgroup CA), CNA (subgroup CB) or observation only (subgroup C0).

All participants participating in the study and registry will be asked to complete questionnaires on health-related quality of life (EQ-5D-5L, SF-36), symptoms of bradycardia (VAS), fatigue (MFIS), depression (HADS-M) and sleep (ESS, AIS-8) at 0, 6, 12 months.

The safety of the interventions will be assessed on a monthly basis (telemedicine and standard follow-up visits), with monitoring of major adverse cardiovascular events (MACE). All events will be resolved by the Central Investigation Safety Committee, which does not include members of the Investigation Steering Committee.

Conditions

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Atrioventricular Block

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

multicenter, noncommercial, physician-initiated, proof-of-concept, prospective, randomized, controlled trial and registry
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group A - PACEMAKER

Group A, n=50 patients aged 18-75 years with indications for elective PM implantation according to the 2021 ESC guidelines for cardiac pacing due to paroxysmal or persistent AVB with a positive results of atropine test.

Group A is early elective pacemaker implantation (PM) strategy in functional AVB.

Group Type ACTIVE_COMPARATOR

Pacemaker implantation

Intervention Type PROCEDURE

Elective pacemaker implantation (DDDR) for functional AVB according to the 2021 ESC Guidelines for Cardiac Pacing

Group B - CARDIONEUROABLATION

Group B, n=50 patients aged 18-75 years with indications for elective PM implantation according to the 2021 ESC guidelines for cardiac pacing due to paroxysmal or persistent AVB with a positive results of atropine test.

Group B will undergo strategy of postponed/deferred PM implantation in functional AVB. Patients wil be implanted and monitored with ILR (in case of severe symptomatic AVB always the emergency system will be called). After cardiovascular autonomic testing (CAT), electrophysiological study (EPS), extra cardiac vagal nerve stimulation (ECVS) and cardioneuroablation will be performed. If CNA is succesful, pacemaker implantation will be cancelled. If CNA is unsuccessful, second session of CNA will be planned. In case of inefficient second attempt, patients will be referred for PM implantation. They will cross-over to PACEMAKER arm.

Group Type ACTIVE_COMPARATOR

Cardioneuroablation (CNA)

Intervention Type PROCEDURE

Experimental method; elective implantable loop recorder (ILR) and biatrial, binodal, atomically and electroanatomically guided CNA with extracardiac vagal nerve stimulation (ECVS) prior and after procedure monitoring (disappearance of ECVS-induced AVB with the goal of achieving post-procedure and maintaining a target heart rate \> 50 beats per minute). CNA procedure is performed with radio-frequency generators and irrigated catheters and with support of 3D-electroanatomic mapping system.

CNA group will receive external ECG recorders. The major reason for external ECG recorders is to provide documentation of clinical AVB, as well as monitoring of patients before and after CNA (or PM implantation, if accepted). In case of severe AVB symptoms always the emergency system will be called.

Interventions

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Pacemaker implantation

Elective pacemaker implantation (DDDR) for functional AVB according to the 2021 ESC Guidelines for Cardiac Pacing

Intervention Type PROCEDURE

Cardioneuroablation (CNA)

Experimental method; elective implantable loop recorder (ILR) and biatrial, binodal, atomically and electroanatomically guided CNA with extracardiac vagal nerve stimulation (ECVS) prior and after procedure monitoring (disappearance of ECVS-induced AVB with the goal of achieving post-procedure and maintaining a target heart rate \> 50 beats per minute). CNA procedure is performed with radio-frequency generators and irrigated catheters and with support of 3D-electroanatomic mapping system.

CNA group will receive external ECG recorders. The major reason for external ECG recorders is to provide documentation of clinical AVB, as well as monitoring of patients before and after CNA (or PM implantation, if accepted). In case of severe AVB symptoms always the emergency system will be called.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent to participate in the study
2. Age 18-75
3. Indication (at least one) of the European Society of Cardiology (ESC) for elective pacemaker implantation due to isolated (without sinus node dysfunction and bundle branch block) paroxysmal, persistent or reflex atrioventricular block:

1. Symptomatic first degree AVB (above 300 msec). Class IIaC
2. Symptomatic Mobitz type I second degree AVB. Class IIaC
3. AVB 2:1, even asymptomatic, but not during sleep. Class IIaC
4. Mobitz II type advanced 2nd degree AVB or complete block (3rd degree AVB). Class IC
5. Advanced AVB during AF regardless of symptoms, but not during sleep. Class IC
6. Reflex syncope in patients over 40 years of age with documented pauses within the AVB mechanism, symptomatic (\>3 sec) or asymptomatic \>6 sec. Class IC
7. Reflex syncope in patients over 40 years of age with documented pauses within AVB mechanism in the course of sick sinus syndrome (CSS). Class IC
8. Reflex syncope in patients over 40 years of age with documented pauses within AVB mechanism during tilt test. Class IC

Exclusion Criteria

1. Implanted pacemaker/ICD/CRT
2. Sinus node dysfunction with indication for pacemaker implantation
3. Planned ablation of the atrioventricular junction
4. Severe prolonged bradycardia in advanced AVB requiring intravenous drugs and temporary pacing
5. Status post cardiac surgery
6. Acute myocardial infarction and heart failure (not related to bradycardia)
7. Status post percutaneous valvular intervention or ablation
8. Acute infection or any other accompanying disease which is contraindication to percutaneous procedures and/or implantation of a pacemaker
9. Pregnancy, nursing or planned pregnancy within 12 months
10. Decompensated chronic diseases (endocrine disorders, electrolyte disorders, etc.)
11. Advanced cardiomyopathies with indication for ICD implantation in primary or secondary prevention of sudden cardiac death (SCD)
12. Advanced ventricular arrhythmias with indication for ICD implantation in primary or secondary prevention of SCD
13. Persistent right or left bundle branch block
14. Musculoskeletal diseases with separate indications for pacemaker implantation
15. Contraindications to the procedures used in the study
16. The presence of a mental illness or limitation of cognitive functions that prevent independent participation in the study, including the use of telemedicine services
17. Any abnormality found that is considered by the Principal Investigator a contraindication to participate in the stidy due to data interpretation or safety issue
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Heart of Poland

OTHER

Sponsor Role lead

Responsible Party

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Sebastian Stec

Clinical Professor, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sebastian M Stec, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

American Heart of Poland

Edyta Stodolkiewicz-Nowarska, MD, PhD

Role: STUDY_DIRECTOR

American Heart of Poland

Krzysztof Milewski, MD, PhD

Role: STUDY_CHAIR

American Heart of Poland

Locations

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American Heart of Poland

Dąbrowa Górnicza, , Poland

Site Status RECRUITING

American Heart of Poland

Mielec, , Poland

Site Status RECRUITING

Countries

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Poland

Central Contacts

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Sebastian M Stec, MD, PhD

Role: CONTACT

+48 600-298-022

Edyta Stodolkiewicz-Nowarska, MD PhD

Role: CONTACT

+48 785-885-425

Facility Contacts

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Sebastian Stec, MD, PhD

Role: primary

+48 600 298 022

Sebastian Stec, MD, PhD

Role: primary

+48 600 298 022

References

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Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, Fedorowski A, Furlan R, Kenny RA, Martin A, Probst V, Reed MJ, Rice CP, Sutton R, Ungar A, van Dijk JG; ESC Scientific Document Group. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018 Jun 1;39(21):1883-1948. doi: 10.1093/eurheartj/ehy037. No abstract available.

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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.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 20806214 (View on PubMed)

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Reference Type BACKGROUND
PMID: 28106018 (View on PubMed)

Baysal E, Guler TE, Gopinathannair R, Bozyel S, Yalin K, Aksu T. Catheter Ablation of Atrioventricular Block: From Diagnosis to Selection of Proper Treatment. JACC Case Rep. 2020 Sep 15;2(11):1793-1801. doi: 10.1016/j.jaccas.2020.07.050. eCollection 2020 Sep.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 34186197 (View on PubMed)

Josiak K, Stec S, Zysko D, Skonieczny B, Kosior J, Sledz J, Wilczek A, Stodolkiewicz-Nowarska E, Biel B, Szymkiewicz P, Skoczynski P, Karbarz D, Ludwik B, Banasiak W, Jagielski D. Safety and efficacy of His bundle pacing validated by extracardiac vagal nerve stimulation (HIS-STORY). Cardiol J. 2022;29(4):698-701. doi: 10.5603/CJ.a2022.0053. Epub 2022 Jun 15. No abstract available.

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Reference Type BACKGROUND
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Gajda R, Knechtle B, Gebska-Kuczerowska A, Gajda J, Stec S, Krych M, Kwasniewska M, Drygas W. Amateur Athlete with Sinus Arrest and Severe Bradycardia Diagnosed through a Heart Rate Monitor: A Six-Year Observation-The Necessity of Shared Decision-Making in Heart Rhythm Therapy Management. Int J Environ Res Public Health. 2022 Aug 19;19(16):10367. doi: 10.3390/ijerph191610367.

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Reference Type RESULT
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Osorio TG, Paparella G, Stec S, Chierchia GB, de Asmundis C. Cardiac parasympathetic modulation in the setting of radiofrequency ablation for atrial fibrillation. Arch Med Sci. 2019 Apr 26;17(6):1716-1721. doi: 10.5114/aoms.2019.84717. eCollection 2021.

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Reference Type RESULT
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Other Identifiers

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2022/ABM/03/00035

Identifier Type: -

Identifier Source: org_study_id

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