Cardiac Ganglionated Plexus Ablation Before Permanent Pacemaker Implantation in Patients With Sick Sinus Syndrome (GAPS)

Cardiac Ganglionated Plexus Ablation Before Permanent Pacemaker Implantation in Patients With Sick Sinus Syndrome - A Multicenter, Randomized, Prospective Clinical Trial

Different studies for cardiac ganglionated plexus（GP） ablation to treat vagal vascular syncope, sinus node dysfunction, and functional atrioventricular block have been published. Investigators have developed a more specific approach of cardiac, called cardioneuroablation . This treatment is based on a high-frequency stimulation (HFS) and/or anatomical landmarks to identify GPs in left atrium，which being targeted by radiofrequency catheter ablation. The feasibility of GPs ablation/cardioneuroablation has already been tested in our center in former studies in humans,with a favorable outcome for the patients involved. The results of the former studies have been submitted for publication. However, there are no prospective randomized studies to evaluate the efficacy and safety of atrial ganglionated plexus ablation for SSS before permanent pacemaker implantation.

The purpose of this study of GAPS in humans is to evaluate the efficacy and safety of cardioneuroablation in patients of sick sinus syndrome before they receive a permanent pacemaker.

Study Overview

• Status: Unknown
• Conditions: Sick Sinus Syndrome; Permanent Pacemaker Implantation; Cardioneuroablation; Ganglionated Plexus
• Intervention / Treatment: Procedure: cardiac ganglion plexus ablation(cardioneuroablation); Device: Permanent pacemaker implantation

Detailed Description

This is a multicenter,prospective, open, interventional study. All patients will undergo permanent pacemaker implantation. The study will involve eight different steps, from the screening procedure through study completion: screening, enrollment, pharmacological testing, randomization of group allocation, preprocedural assessment, procedure, follow-up, study completion. The dedicated study members (cardiac electrophysiologists, statisticians) and the PI are responsible for recording all data from the trial on the case report forms (CRFs) and completing the study database. The participants will be randomly allocated in a 1:1 ratio to either GPs ablation followed by permanent pacemaker implantation or pacemaker alone. Randomization will be conducted centrally by an independent statistics department(Oxford Medical Center of National Center for Cardiovascular Diseases, Beijing, China) and stratified by center and age(<50 or >=50 years); A dedicated independent physician will be responsible for the safety monitoring. The PI will permit inspection of the trial files and the database by national or international official controlling scientific authorities, if required. The PI will review and monitor completed CRFs and the database at regular intervals throughout the trial.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peng Wang, MD; Phone Number: 861088322407; Email: pydiamond@hotmail.com
• Study Contact Backup: Name: Yan Yao, MD,PhD; Phone Number: 861088322401; Email: ianyao@263.net.cn

Study Locations

• China
  • Beijing, China
    • 1Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Beijing
    • Beijing, Beijing, China, 100037
      • China National Center for Cardiovascular Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 73 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sign the informed consent form.
• Diagnosed as SSS, with recurrent symptomatic bradycardia, blackouts, syncope, etc.
• Meet the indications for permanent pacemaker implantation according to the 2018 Chinese pacemaker guidelines (Class I, Class IIa).
• Positive reaction to atropine: The PP interval shortened by more than 20% or the sinus heart rate>60 bpm after intravenous injection of 2 mg of atropine.

Exclusion Criteria:

• Age <14 years old or >75 years old.
• Accompanied with complex congenital heart disease, valvular heart disease, cardiomyopathy and other chronic diseases, such as heart failure (NYHA grade III or IV).
• Acute coronary syndrome or myocardial infarction occurred within 6 months. Cerebrovascular events (such as transient ischemic attack, stroke) or other cerebral blood supply disorders occurred within 3 months.
• History of cardiac surgery and/or permanent cardiac pacemaker implantation.
• TEE or CT found a left atrial thrombus and/or left atrial anteroposterior diameter > 55mm or LVEF < 35%.
• Persistent atrial fibrillation, high-degree or complete atrioventricular block; double or triple fascicular block.

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
Experimental: Ablation group(Ablation+pacemaker); The cardioneuroablation will be performed under conscious sedation. After 3-dimensional endocardial surface of the LA and pulmonary veins have been constructed by Ensite system, the GP sites can be located in LA；High frequecy stimulation（HFS）will be used to conform if there is a positive vagal response at each GP site. The upper limits of power and temperature will be set to 30-40 W and 43-60°C, respectively. And if no vagal response been induced during ablation, radiofrequency will be delivered for 30 seconds and stopped in this site. The end point of the ablation procedure will be that no vagal response could be induced by repeat HFS. After ablation of GPs, the participants will receive permanent pacemaker implantation(see arm of control group).	Procedure: cardiac ganglion plexus ablation(cardioneuroablation); Cardiac ganglion plexus ablation in the left atrium will be performed before implanting permanent pacemaker in patients with sick sinus syndrome.; Device: Permanent pacemaker implantation; DDD permanent pacemaker will be implanted in the paticipants.; Other Names: St. Jude Medical or Medtronic
Sham Comparator: Control group(only pacemaker); The control group only treated with permanent pacemaker without cardioneuroablation.The participants will receive permanent pacemaker implantation, the pacemaker placement will be done in accordance with standards at each center. All implanted pacemakers are provided two manufacturers (St. Jude Medical or Medtronics), His bundle pacing will be recommended in patients with a LVEF between 35%-45%. After placement of permanent pacemaker, the participants will be followed-up at 1 week, 3,6,12 months. After the permanent pacemaker implantation, the rate response function should be turned off and low pacing rate should be set at 60bpm uniformly in all the eligible participants.	Device: Permanent pacemaker implantation; DDD permanent pacemaker will be implanted in the paticipants.; Other Names: St. Jude Medical or Medtronic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of atrial pacing of permanent pacemaker programming	Percentage of atrial pacing of permanent pacemaker at 12 months after the implantation of permanent pacemaker with program control.	12 months （±14 days）
Percentage of pacing of paced rhythm in Holter record	Percentage of pacing of paced rhythm in Holter record 1week after pacemaker implantation	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of sinus rhythm beats in Holter records	Percentage of sinus rhythm beats at 1 week, 3 months, 6 months and 12 months with Holter.	1 week, 3 months(±5 days), 6 months (±7 days)，12 months （±14 days）
Freedom from syncope	Freedom from sycope at 1 week, 3 months, 6 months and 12 months with outpatient clinic follow up.	1 week, 3 months(±5 days), 6 months (±7 days)，12 months （±14 days）
Improvement of quality of life: Short Form-36 (SF-36) or Euroqol (EQ-5D)	Improvement of quality of life with questionair at 1 week, 3 months, 6 months and 12 months with outpatient clinic follow up.	1 week, 3 months(±5 days), 6 months (±7 days)，12 months （±14 days）

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Collaborators: Chinese Academy of Medical Sciences, Fuwai Hospital; Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital South Campus; Heart Center of The First Affiliated Hospital of Xinjiang Medical Unviersity

Publications and helpful links

General Publications

• Qin M, Zhang Y, Liu X, Jiang WF, Wu SH, Po S. Atrial Ganglionated Plexus Modification: A Novel Approach to Treat Symptomatic Sinus Bradycardia. JACC Clin Electrophysiol. 2017 Sep;3(9):950-959. doi: 10.1016/j.jacep.2017.01.022. Epub 2017 Apr 26.
• Debruyne P, Rossenbacker T, Collienne C, Roosen J, Ector B, Janssens L, Charlier F, Vankelecom B, Dewilde W, Wijns W. Unifocal Right-Sided Ablation Treatment for Neurally Mediated Syncope and Functional Sinus Node Dysfunction Under Computed Tomographic Guidance. Circ Arrhythm Electrophysiol. 2018 Sep;11(9):e006604. doi: 10.1161/CIRCEP.118.006604.
• Cui B, Lu Z, He B, Hu X, Wu B, Xu S, Huang C, Jiang H. Acute effects of ganglionated plexi ablation on sinoatrial nodal and atrioventricular nodal functions. Auton Neurosci. 2011 Apr 26;161(1-2):87-94. doi: 10.1016/j.autneu.2011.01.004.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 28, 2019
• Primary Completion (Anticipated): October 27, 2020
• Study Completion (Anticipated): October 27, 2021

Study Registration Dates

• First Submitted: October 26, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Sick Sinus Syndrome; Ganglionated plexus; Cardioneuromablation; Pacing percentage
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Arrhythmia, Sinus; Heart Block; Syndrome; Sick Sinus Syndrome
• Other Study ID Numbers: 20191026

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