Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block)

Heart Failure Clinical Trial

— LEAP-Block  

Official title:

Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block): A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04730921
• Other study ID #: 2020-1379
• Status: Recruiting
• Phase: N/A
• Start date: November 13, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Fu Wai Hospital, Beijing, China
• Contact: Xiaofei Li, M.D.
• Phone: +8617801013995
• Email: lixiaofei0103[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized controlled study. The aim of this study is to compare the impact of LBBAP on left ventricular function as compared with traditional right ventricular pacing in patients with atrioventricular block.

Description:

LEAP-BLOCK is a prospective, multi-center, randomized controlled trial that is designed to determine whether left bundle branch area pacing (LBBAP) may reduce the risk of RV ventricular pacing induced cardiac dysfunction as compared with traditional RV pacing (RVP) in patients with atrioventricular (AV) block and normal LV function (LVEF≥50%) who require high percent of ventricular pacing. The primary aim of this trial is to compare the time to first event (composite of all-cause mortality and newly heart failure hospitalization and device upgrade due to heart failure) between LBBAP and RVP group in patients with AV block. Patients with AV block and normal LV function who require high burden of ventricular pacing (expected >40%) will be randomized to LBBAP or RVP group for therapy. Patients will be followed at least every 3 months for clinical status and every 6 months for echocardiographic evaluation until the study closure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 458
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• a. Adult patients aged 18-90;
• b. AV block patients with ventricular pacing indications and the expected rate of ventricular pacing(VP)> 40%, including (a)Third-degree AV block; (b) Second degree AV block (type II); (c) intermittent advanced AV block with expected VP>40%; (d)Symptomatic first degree AV block and PR interval on ECG = 250ms;
• c. The subject is able to receive a pectoral implant;
• d. The subject is willing and able to comply with the protocol;
• e. The subject is expected to remain available for follow-up visits at the study centers.
• f. Subject or authorized legal guardian or representative has signed and dated the study Subject Informed Consent

Exclusion Criteria:

• a. Baseline echocardiographic assessment of patients with impaired LV function (LVEF<50%);
• b. Having difficulties in follow-up: Those who cannot accept 2-year follow-up on time due to physical condition or other reasons;
• c. Patients with persistent atrial fibrillation;
• d. Pacemaker replacement without new implanted ventricular electrodes;
• e. Patients with implantable cardioverter-defibrillator (ICD) indications;
• f. Surgery is required within 1 year due to severe structural heart disease;
• g. Patients with tricuspid mechanical valve replacement, or congenital heart disease (including transposition of the great arteries, or permanent left superior vena cava, etc), or AV block resulting from: (a) Hypertrophic cardiomyopathy(HCM)vpost (modified) Morrow surgery, (b) ventricular septal defect repair; and those who are unlikely to achieve successful LBBAP procedure.

Related Conditions & MeSH terms

• Atrioventricular Block
• Heart Failure
• Left Bundle Branch Area Pacing
• Right Ventricular Pacing

Intervention

Device:
• Left bundle branch area pacing
Left bundle branch area pacing(LBBAP) is a novel physiological pacing form for ventricular pacing. In patients received LBBAP, the pacing lead will be placed at left bundle branch area to achieve narrow paced QRS duration.
• Right ventricular pacing
Right ventricular pacing is the traditional pacing modality for ventricular pacing. The pacing lead was placed in the apex or septum of right ventricle.

Locations

Country	Name	City	State
China	Beijing Anzhen hospital, Capital Medical University	Beijing	Beijing
China	Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Teda International Cardiovascular Hospital	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Fuwai Central China Cardiovascular Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (14)

Lead Sponsor

Collaborator

Fu Wai Hospital, Beijing, China

Affiliated Hospital of Qinghai University, Beijing Anzhen Hospital, Beijing Friendship Hospital, Chinese Society of Cardiology, First Affiliated Hospital of Chongqing Medical University, Fuwai Central China Cardiovascular Hospital, Peking Union Medical College Hospital, Peking University First Hospital, Shanxi Cardiovascular Hospital, Teda International Cardiovascular Hospital, Tianjin, China, The First Affiliated Hospital of Zhengzhou University, The Second Hospital of Hebei Medical University, Tianjin Medical University General Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

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

Cho SW, Gwag HB, Hwang JK, Chun KJ, Park KM, On YK, Kim JS, Park SJ. Clinical features, predictors, and long-term prognosis of pacing-induced cardiomyopathy. Eur J Heart Fail. 2019 May;21(5):643-651. doi: 10.1002/ejhf.1427. Epub 2019 Feb 8. — 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

Li X, Li H, Ma W, Ning X, Liang E, Pang K, Yao Y, Hua W, Zhang S, Fan X. Permanent left bundle branch area pacing for atrioventricular block: Feasibility, safety, and acute effect. Heart Rhythm. 2019 Dec;16(12):1766-1773. doi: 10.1016/j.hrthm.2019.04.043. Epub 2019 Apr 29. — View Citation

Li X, Qiu C, Xie R, Ma W, Wang Z, Li H, Wang H, Hua W, Zhang S, Yao Y, Fan X. Left bundle branch area pacing delivery of cardiac resynchronization therapy and comparison with biventricular pacing. ESC Heart Fail. 2020 Aug;7(4):1711-1722. doi: 10.1002/ehf2.12731. Epub 2020 May 13. — View Citation

Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm. 2015 Feb;12(2):305-12. doi: 10.1016/j.hrthm.2014.10.021. Epub 2014 Oct 22. — View Citation

Tayal B, Fruelund P, Sogaard P, Riahi S, Polcwiartek C, Atwater BD, Gislason G, Risum N, Torp-Pedersen C, Kober L, Kragholm KH. Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study. Eur Heart J. 2019 Nov 21;40(44):3641-3648. doi: 10.1093/eurheartj/ehz584. — View Citation

Vijayaraman P, Dandamudi G. Anatomical approach to permanent His bundle pacing: Optimizing His bundle capture. J Electrocardiol. 2016 Sep-Oct;49(5):649-57. doi: 10.1016/j.jelectrocard.2016.07.003. Epub 2016 Jul 11. — View Citation

Vijayaraman P, Naperkowski A, Subzposh FA, Abdelrahman M, Sharma PS, Oren JW, Dandamudi G, Ellenbogen KA. Permanent His-bundle pacing: Long-term lead performance and clinical outcomes. Heart Rhythm. 2018 May;15(5):696-702. doi: 10.1016/j.hrthm.2017.12.022. Epub 2017 Dec 20. — View Citation

Yu CM, Chan JY, Zhang Q, Omar R, Yip GW, Hussin A, Fang F, Lam KH, Chan HC, Fung JW. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med. 2009 Nov 26;361(22):2123-34. doi: 10.1056/NEJMoa0907555. Epub 2009 Nov 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pre-existing heart disease based primary outcome	All-cause death and/or hospitalization for heart failure comparison based on pre-exsiting heart disease (e.g. coronary heart disease, atrial fibirllation, valvular heart disease, and dilated cardiomyopathy.	Within 2 years after device implantation
Other	Baseline QRSd based primary outcome	All-cause death and/or hospitalization for heart failure comparison based on baseline QRSd (>120ms vs. =120ms)	Within 2 years after device implantation
Primary	The primary endpoint is the time to a first event of composite outcomes, including all-cause death, hospitalization for heart failure, and an upgrade to cardiac resynchronization therapy due to pacing induced heart failure.	All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: 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 medication therapy.; Upgrade to cardiac resynchronization therapy (CRT): Upgrade from dual-chamber pacemaker to CRT-Pacemaker/CRT-Defibrillator due to impaired LV function (LVEF decrease to 40% or less).	Within two years after device implantation
Secondary	Rate of the composite outcomes of all-cause death and/or hospitalization for heart failure	All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: 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 medication therapy.	Within 2 years after device implantation
Secondary	Rate of the composite outcomes of hospitalization for heart failure and/or an upgrade to cardiac resynchronization therapy due to pacing induced heart failure.	Hospitalization for heart failure: 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 medication therapy.; Upgrade to cardiac resynchronization therapy: Upgrade from dual chamber pacemaker to CRT-P/CRT-D due to impaired LV function (LVEF decrease to 40% or less).	Within 2 years after device implantation
Secondary	Rate of the composite outcomes of LVEF <50%, and/or an increase in LVESV =15% during follow-up as compared with the value at randomization	Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and/or the LVESV is increased by 15% or more.	Within 2 years after device implantation
Secondary	The value of LVEF and LVESV assessed by echocardiography at 1-year and 2-year follow-up	Echocardiography will be assessed at 1-year, and 2-year follow-up and the absolute value of LVEF and LVESV will be compared between two groups.	24 months
Secondary	The time to a first event of LVEF <50% and decrease in LVEF by = 10% during 2 years follow-up as compared with the value at randomization.	Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and decreased by 15% or more as compared with the value at randomization.	24 months
Secondary	The immediate success rate of the LBBAP procedure	Successful LBBAP procedure is identified according to ECG and intracardiac electrogram (IEGM) during the procedure. All LBBAP procedures will be categorized as selective left bundle branch pacing (S-LBBP), non-selective left bundle branch pacing(NS-LBBP), or left ventricular septal pacing (LVSP).	1 weeks
Secondary	The rate of procedure and Device related complications	Procedure complications include pneumothorax, hemothorax, and air embolism. Device related complications include lead and pocket complications.	24 months
Secondary	Changes in Pacing parameters and ECG characteristics.	Pacing parameters include pacing thresholds (ventricle), Sense ampitude (ventricle), Impedance (ventricle). ECG characteristics include paced QRS duration and QRS morphology, etc.	24 months
Secondary	The occurrence of LV dyssynchrony	The occurrence of LV dyssynchrony will be evaluated by echocardiography during 2-year follow-up.	24 months
Secondary	Atrial high-rate episodes recorded by the pacemaker	Atrial high-rate episodes recorded in the pacemaker will be followed during two years of follow-up	24 months
Secondary	The long-term success rate of LBBAP	In LBBAP group, the successful LBBAP will be identified according ECG features at 2-years follow-up	24 months