PReventive Effect Of Left Bundle Branch Area Pacing Versus righT vEntricular paCing on All Cause deaTh, Heart Failure Progression, and Ventricular dysSYNChrony in Patients With Substantial Ventricular Pacing (PROTECT-SYNC): Multicenter Prospective Randomized Controlled Trial

Atrioventricular Block Clinical Trial

Official title:

PReventive Effect Of Left Bundle Branch Area Pacing Versus righT vEntricular paCing on All Cause deaTh, Heart Failure Progression, and Ventricular dysSYNChrony in Patients With Substantial Ventricular Pacing (PROTECT-SYNC): Multicenter Prospective Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05585411
• Other study ID #: 4-2022-0824
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: November 1, 2026

Study information

• Verified date: October 2023
• Source: Yonsei University
• Contact: TaeHoon Kim
• Phone: +82 02-2228-8467
• Email: thkimcardio[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PROTECT-SYNC study is a multicenter, randomized, controlled trial. A total of 7 medical centers across Republic of Korea will enroll 450 patients during 2 years of enrollment period, and followed for 2 years of follow-up period. The purpose of this study to compare the clinical outcomes of Left Bundle Branch Area Pacing (LBBAP) compared to Right Ventricular Pacing (RVP) in bradyarrhythmia patients who require high burden of ventricular pacing (>40%).

Description:

PROTECT-SYNC study is a multicenter, randomized, controlled trial that is designed to assess whether LBBAP may reduce the risk of composite primary endpoint including all cause mortalty, HF hospitalization and/or urgent HF related visit, occurrence of pacing induced CMP, and CRT-upgrade event, compared to RVP in patients who require substantial (>40%) ventricular pacing. Patients who require pacemaker and substantial (>40%) ventricular pacing will be randomized to LBBAP or RVP group, and a total of 7 medical centers across Republic of Korea will enroll 450 patients during 2 years of enrollment period, and followed for 2 years of follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. At least 19 years old and willing and capable to give informed consent

2. Patients who is willing and able to comply with the prescribed follow-up tests and schedule of evaluations.

3 Scheduled to receive a pacemaker implant 4. Substantial percentage of V pacing rate (>40%) is anticipated

Exclusion criteria:

1. Incapacitated or unable to read or write

2. Patient who is an indication of ICD or CRT

3. History of prosthetic valve surgery on tricuspid valve

4. Prior myocardial infarction including ventricular septum

5. Life expectancy < 12 months due to any condition

6. Unavailable for at least 24 months of follow-up visits

7. Pregnant or breastfeeding at the time of signing consent

8. Prior Heart transplant surgery

9. Persistent Left Superior Vena Cava (PLSVC)

Related Conditions & MeSH terms

• Atrioventricular Block
• Bradyarrhythmia
• Bradycardia
• Heart Failure
• Left Bundle Branch Area Pacing

Intervention

Procedure:
• Left bundle branch area pacing
LBBAP success is defined if ventricular lead is successfully placed at interventricular septum and RBB configuration observed during unipolar tip pacing. LBB capture is defined if fulfilling criterion 1 and at least one in criteria 2. RBBB configuration observed during unipolar tip pacing One of the following should be met: Abrupt shortening of Stim-LVAT (stimulus to peak of the R wave in V6 [LV activation time]) of >10ms during increasing output Short and constant stim-LVAT and the shortest stim-LVAT <75ms in non-LBBB and <85ms in LBBB Programmed stimulation by pacing lead changes QRS morphology from nonselective LBB to LV septal capture LBB potential (LBB-V interval of 15 to 35ms) Transition from nonselective LBB capture to selective LBB capture at near threshold outputs If criterion 1 is fulfilled but none in criteria 2 is met, the procedure is considered to be deep septal pacing (DSP).
• Right ventricular pacing
Right ventricular pacing is the traditional pacing modality for ventricular pacing. Implantation of a RV pacing lead (apex or septum of right ventricle) will be attempted using the standard-of-care technique first

Locations

Country	Name	City	State
Korea, Republic of	Bucheon Sejong Hospital	Bucheon
Korea, Republic of	GyeongSang National University Changwon Hospital	Changwon
Korea, Republic of	Chungbuk National University Hospital	Chungju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kyunghee University hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H, Oren JW, Dandamudi G, Vijayaraman P. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol. 2018 May 22;71(20):2319-2330. doi: 10.1016/j.jacc.2018.02.048. Epub 2018 Mar 10. — View Citation

Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L, Shinn T, Sutton MS; Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med. 2013 Apr 25;368(17):1585-93. doi: 10.1056/NEJMoa1210356. — View Citation

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. Erratum In: Eur Heart J. 2022 May 1;43(17):1651. — View Citation

Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Mao G, Vijayaraman P, Ellenbogen KA. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart. 2019 Jan;105(2):137-143. doi: 10.1136/heartjnl-2018-313415. Epub 2018 Aug 9. — View Citation

Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2019 Aug 20;140(8):e382-e482. doi: 10.1161/CIR.0000000000000628. Epub 2018 Nov 6. No abstract available. Erratum In: Circulation. 2019 Aug 20;140(8):e506-e508. — View Citation

Sharma PS, Patel NR, Ravi V, Zalavadia DV, Dommaraju S, Garg V, Larsen TR, Naperkowski AM, Wasserlauf J, Krishnan K, Young W, Pokharel P, Oren JW, Storm RH, Trohman RG, Huang HD, Subzposh FA, Vijayaraman P. Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry. Heart Rhythm. 2022 Jan;19(1):3-11. doi: 10.1016/j.hrthm.2021.08.033. Epub 2021 Sep 3. Erratum In: Heart Rhythm. 2023 Jul;20(7):1100. — View Citation

Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA; MOde Selection Trial Investigators. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation. 2003 Jun 17;107(23):2932-7. doi: 10.1161/01.CIR.0000072769.17295.B1. Epub 2003 Jun 2. — View Citation

Tops LF, Schalij MJ, Bax JJ. The effects of right ventricular apical pacing on ventricular function and dyssynchrony implications for therapy. J Am Coll Cardiol. 2009 Aug 25;54(9):764-76. doi: 10.1016/j.jacc.2009.06.006. — View Citation

Tse HF, Lau CP. Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol. 1997 Mar 15;29(4):744-9. doi: 10.1016/s0735-1097(96)00586-4. — View Citation

Vijayaraman P, Ponnusamy S, Cano O, Sharma PS, Naperkowski A, Subsposh FA, Moskal P, Bednarek A, Dal Forno AR, Young W, Nanda S, Beer D, Herweg B, Jastrzebski M. Left Bundle Branch Area Pacing for Cardiac Resynchronization Therapy: Results From the International LBBAP Collaborative Study Group. JACC Clin Electrophysiol. 2021 Feb;7(2):135-147. doi: 10.1016/j.jacep.2020.08.015. Epub 2020 Oct 28. — View Citation

Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A; Dual Chamber and VVI Implantable Defibrillator Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA. 2002 Dec 25;288(24):3115-23. doi: 10.1001/jama.288.24.3115. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	composite of all-cause death, heart failure hospitalization, occurrence of pacing induced cardiomyopathy, and an upgrade to cardiac resynchronization therapy	All-cause death: including cardiovascular and non-cardiovascular deaths.; Heart failure hospitalization: An unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy.; Occurrence of Pacing induced cardiomyopathy : LVEF <50% and absolute LVEF decline =10% or increase in LVESV =15% Upgrade to cardiac resynchronization therapy (CRT): Upgrade from pacemaker to CRT-Pacemaker/CRT-Defibrillator due to impaired LV function (LVEF decrease to 40% or less).	during 2 years after pacemaker implantation
Secondary	all cause mortality	All cause deaths including cardiovascular and non-cardiovascular deaths.	during 2 years after pacemaker implantation
Secondary	Cardiovascular mortality	Cardiovascular death	during 2 years after pacemaker implantation
Secondary	Heart failure hospitalization	An unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy.	during 2 years after pacemaker implantation
Secondary	success rate of LBBAP implantation	LBBAP success is defined if ventricular lead is successfully placed at interventricular septum and RBB configuration observed during unipolar tip pacing.	during 3days after pacemaker implantation
Secondary	LBBAP related complications	Loss of lead function or need for lead revision, extraction, replacement for any reason	during 2 years after pacemaker implantation
Secondary	LBB capture failure	failed LBB capture, confirmed by investigator	during 2 years after pacemaker implantation
Secondary	Short-term procedure and Device related complications	composite of device and procedure related complications until 7 days after procedure	during 1wk after pacemaker implantation
Secondary	Long-term procedure and Device related complications	composite of device and procedure related complications after 7 days after procedure	during 1wk after pacemaker implantation
Secondary	Rate of LV systolic dysfunction	LVEF <50% and absolute reduction in LVEF >10%, and/or an increase in LVESV =15%.	6month and 2yr after pacemaker implantation
Secondary	Changes in cardiopulmonary exercise test parameters	(VO2 peak, Exercise intensity, Peak Respiratory Exchange Ratio (Peak RER), Exercise time, age predicted aerobic capacity, VE/VCO2 slope, Lactate threshold, Max predicted HR, Max HR / Max predicted HR, presence of ST change , AF at Baseline, Incident AF during exercise	6month and 2yr after pacemaker implantation
Secondary	Incidental atrial fibrillation	Newly developed atrial fibrillation in patients without documented atrial fibrillation	during 2 years after pacemaker implantation