Clinical trial NCT04730921: Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block)
Official title: Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrioventricular Block
Left Bundle Branch Area Pacing
Right Ventricular Pacing
Heart Failure
Keywords: Atrioventricular Block
Left bundle branch area pacing
Right ventricular pacing
Lead sponsor: Fu Wai Hospital, Beijing, China
Sponsor class: OTHER
Collaborators: name: Beijing Anzhen Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: The Second Hospital of Hebei Medical University
name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Tianjin Medical University General Hospital
name: TEDA International Cardiovascular Hospital
name: Peking Union Medical College Hospital
name: Chinese Society of Cardiology
name: Affiliated Hospital of Qinghai University
name: Shanxi Cardiovascular Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Peking University First Hospital
name: Beijing Friendship Hospital
First posted: 2021-01-29
Enrollment: 458
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Within two years after device implantation
Secondary outcomes:
measure: Rate of the composite outcomes of all-cause death and/or hospitalization for heart failure
timeFrame: Within 2 years after device implantation
measure: Rate of the composite outcomes of hospitalization for heart failure and/or an upgrade to cardiac resynchronization therapy due to pacing induced heart failure.
timeFrame: Within 2 years after device implantation
measure: 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
timeFrame: Within 2 years after device implantation
measure: The value of LVEF and LVESV assessed by echocardiography at 1-year and 2-year follow-up
timeFrame: 24 months
measure: 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.
timeFrame: 24 months
measure: The immediate success rate of the LBBAP procedure
timeFrame: 1 weeks
measure: The rate of procedure and Device related complications
timeFrame: 24 months
measure: Changes in Pacing parameters and ECG characteristics.
timeFrame: 24 months
measure: The occurrence of LV dyssynchrony
timeFrame: 24 months
measure: Atrial high-rate episodes recorded by the pacemaker
timeFrame: 24 months
measure: The long-term success rate of LBBAP
timeFrame: 24 months
Other outcomes:
measure: Pre-existing heart disease based primary outcome
timeFrame: Within 2 years after device implantation
measure: Baseline QRSd based primary outcome
timeFrame: Within 2 years after device implantation
Locations:
city: Beijing
country: China
facility: Beijing Anzhen hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Fuwai Central China Cardiovascular Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Teda International Cardiovascular Hospital
state: Tianjin
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Xiaohan Fan, PhD.
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.
citation: 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.
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.
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.
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.
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.