Permanent Pacemaker Implantation or Cardioneuroablation in Sinus Node Dysfunction (SANOK)

Comparison of Strategies for Permanent Pacemaker Implantation and/or Cardioneuroablation in Patients With Sinus Node Dysfunction: a Noncommercial Physician-initiated Randomized Controlled Trial

This is a noncommercial, physician-initiated, monitored, multicenter, prospective randomized clinical trial, a proof-of-concept study, investigating a treatment strategy only. The study will use medical products applied for invasive and nonivasive procedures performed at the participating centers.

Study Overview

• Status: Recruiting
• Conditions: Sinus Node Dysfunction
• Intervention / Treatment: Procedure: Permament pacemaker implantation; Procedure: Cardioneuroablation

Detailed Description

All patients meeting the inclusion criteria and not meeting the exclusion criteria will be invited to participate in the study. The patient will receive an informed consent form describing the study protocol. After speaking to the investigator and receiving detailed answers to all questions, the patient will sign the written informed consent form to participate in the study or will choose to opt out of randomization and to be included in the registry only.

Premenopausal women who will provide consent to participate in the study will undergo a pregnancy test before any invasive procedure. During the 12-month study duration, the use of effective contraception is recommended.

The patient will be asked to complete the questionnaires on bradycardia symptoms and quality of life (QOL).

Any patient included in the study will be randomized into group A or group B. Patients included in the registry (group C) will undergo patient-tailored interventions and treatments through shared decision-making with a possibility of permanent cardiac pacing (subgroup CA), vagal nerve stimulation (VNS) according to the protocol and cardioneuroablation (subgroup CB), as well as observation (subgroup CO).

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastian Stec, MD, PhD; Phone Number: +48600298022; Email: smstec@wp.pl
• Study Contact Backup: Name: Edyta Stodółkiewicz-Nowarska, MD PhD; Phone Number: 785885425; Email: edytastod@gmail.com

Study Locations

• Poland
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Not yet recruiting
    • Center of Interventional Cardiology, Electrotherapy and Angiology G.V.M. Carint
    • Contact: Janusz Sledz, MD; Phone Number: +48 602535589; Email: januszsledz@onet.eu
    • Principal Investigator: Janusz Sledz, MD
  • Rzeszów, Poland
    • Recruiting
    • Medical Center SABAMED
    • Contact: Agnieszka Reichert, MD; Phone Number: +48 69365129; Email: agarei@mp.pl
    • Principal Investigator: Agnieszka Reichert, MD
  • Sanok, Poland, 38-500
    • Recruiting
    • Subcarpatian Center for Cardiovascular Interventions, Laboratory of Electrophysiology, Cardioneuroablation, Ablation, Arrhythmia and Heart Electrostimulation, G.V.M. Carint
    • Contact: Antoni Wileczek, MD; Phone Number: +48 663517874; Email: antoniwileczek@gmail.com
    • Principal Investigator: Sebastian Stec, MD, PhD
  • Wroclaw, Poland, 50-07
    • Not yet recruiting
    • Department of Cardiology, Laboratory of Invasive Electrophysiology, 4th Military Teaching Hospital in Wroclaw
    • Contact: Adrianna Szalonka, BA; Phone Number: +48 535502175; Email: ada.szalonka@interia.pl
    • Principal Investigator: Dariusz Jagielski, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age, 18-75 years
• Sinus node dysfunction/disease fulfilling criteria for elective pacemaker implantation according to current ESC guidelines (I, IIa, and IIb )
• Optimization of chronic disease treatment
• Ability to provide informed consent to participate in the study
• Ability to understand patient information.

Exclusion Criteria:

• Contraindications to invasive and noninvasive procedures used in the study
• Uncontrolled endocrine and systemic disorders
• Persistent atrial fibrillation
• Dilated cardiomyopathy
• Severe congenital heart valve disease or cardiomyopathy
• Functional NYHA class III/IV
• Left ventricular ejection fraction <35%
• Left atrial diameter >50 mm
• Previous catheter ablation
• Contraindications to anticoagulant treatment
• Contraindications to catheter ablation
• Chronic, advanced two- or third-degree atrioventricular block associated with structural heart disease
• Contraindications to noninvasive tests
• Pregnancy and lactation
• Previous cardiac surgery
• Implanted pacemaker device
• Neck and chest abnormalities
• Myocardial infarction in the previous 6 months
• Percutaneous coronary intervention in the previous 3 months
• Estimated survival <24 months
• Participation in another drug or medical device program
• Limited capacity to understand the study protocol or psychological disorders precluding informed consent to participate in the study.
• Any other uncontrolled chronic diseases, neck and chest abnormalities, or disorders that constitute a contraindication to catheter ablation, antiarrhytmic treatment, general anesthesia, or extracardiac vagal nerve stimulation (ECANS)
• Severe obesity (body mass index ≥40 kg/m2 )

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A - PACEMAKER; According with ESC indications for elective pacemaker implantation due to SND will referred for PM implantation.	Procedure: Permament pacemaker implantation; PM implantation
Experimental: Group B - CARDIONEUROABLATION; According with ESC indications for elective PM implantation due to SND will referred for ICM/ILR implantation or prolonged ECG monitoring. Within 4 weeks patient will be screened by interdisciplinary team and autonomic tests (including atropine tests) will be performed. Than, based on atropine tests, electrophysiologic study and extracardiac vagal nerve stimulation, final indication for cardioneuroablation will be established. Biatrial, binodal cardioneuroablation will be performed with anatomical approach with bilateral extra cardiac vagal nerve stimulation during general anesthesia. Than, patient will be closely monitored and indication for PM implantation will be verified.	Procedure: Cardioneuroablation; Biatrial, binodal CNA procedure with anatomical approach will be performed with pre- and post procedural extracardiac vagal nerve stimulation in general anesthesia.; Other Names: Extracardiac vagal nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Freedom From Bradycardia Symptoms at 6 months	Number of participants who had freedom from bradycardia symptoms at 6 months - for all participants - who had CNA versus PM implanation versus no procedure performed. Trial - patient is randomized to standard PM implatantion (Group A) or CNA procedure (Group B). Registry (Group C) - patient refused participation in the trial, and decided to have share-decision making procedure (CNA, PM implanatation) or no intervention at all - taking into account evidence, risk-benefit assesments, expected outcomes and individual patient preferences.	6 months
Number of Participants with Pacemaker Implantation at 6 months	Number of participants with PM implantation at 6 months	6 monhts

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Events of Procedural Complications	Procedural Complications (death, stroke, myocardial infarction, heart failure, conduction abnormalities, pericardial effusion requiring drainage, hematoma, pseudoaneurysm (0-6 month changes)	0-6 months
Number of Participants With Post-ablation Inducibility of Sinus Arrest and/or AV Block by Vagal Nerve Stimulation	Number of participants with post-ablation inducibility of sinus arrest and/or AV block in pre- and post- procedural extracardiac Vagal Nerve stimulation	1 day (peri-procedural)
Effect of CNA on Quality of Life Parameters Based on EQ-5D-5L Questionnaire	EQ-5D-5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored on a scale of 1-5 ponts, that describes the patient's health state. The maximum score of 1 indicates the best health state, higher scores indicate more severe or frequent problems. In addition, there is a visual analogue scale (VAS) to indicate the general health status with 100 indicating the best health, 0 indicating the worst health status.	0, 3, 6, 9, 12 months
Effect of CNA on Quality of Life Parameters Based on SF-36 Questionnaire	SF-36 questionnaire consists of 36 questions that are distributed across eight scales. Each scale is directly transformed into 0-100 scale. The lower the score the more disability, the higher the score the less disability.	0, 3, 6, 9, 12 months
Effect of CNA on Fatigue Based on Modified Fatigue Impact Scale (MFIS)	MFIS is a validated, standardized, 21-item questionnaire, which provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. Total scores range from 0-84. The lower the score the less fatigue, the higher the score the more fatigue impairs physical, cognitive, and psychosocial functioning.	0, 6, 12 months
Effect of CNA on Depression/Anxiety based on Modified Hospital Anxiety and Depression Scale (HADS-M)	HADS-M is a validated, standardized 16-item questionnaire to evaluate the association between anxiety and depression and the degree of illness acceptance in patients. Total scores range from 0-64. Higher scores indicate a greater degree of anxiety or depression.	0, 6, 12 months
Effect of CNA on Sleep Disorders Based on Epworth Sleep Scale (ESS)	The ESS score is a standardized, validated 8-item questionnaire (with scores 0-3 each). The total score can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life.	0, 6, 12 months
Effect of CNA on Sleep Disorders Based on Athens Insomnia Scale-8 (AIS-8)	AIS-8 is a standardized, validated questionnaire assessing 8 factors related to nocturnal sleep and daytime dysfunction, which are rated on a 0-3 scale. The sleep is evaluated from the cumulative score of all factors and reported as an individual's sleep outcome. Higher score indicates more sleep disturbances.	0, 6, 12 months

Collaborators and Investigators

• Sponsor: Stec, Sebastian, MD, PhD, FESC
• Collaborators: KCRI
• Investigators: Study Chair: Sebastian Stec, MD, PhD, Medical Center SABAMED Medicans

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 5, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: quality of life; pacemaker; bradycardia; ECG monitoring; cardioneuroablation; sinus node dysfunction; extracardiac vagal nerve stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Arrhythmia, Sinus; Heart Block; Sick Sinus Syndrome
• Other Study ID Numbers: SANOK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No