Clinical trial NCT06241651: CSP Versus BiVP for Heart Failure Patients with RVP Upgraded to Cardiac Resynchronization Therapy
Official title: Conduction System Pacing Versus Biventricular Pacing for Heart Failure Patients with Right Ventricular Pacing Upgraded to Cardiac Resynchronization Therapy: a Prospective Multicenter Non-inferiority Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Conduction System Pacing
Biventricular Pacing
Cardiac Resynchronization Therapy
Right Ventricular Pacing
Heart Failure
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: The First Affiliated Hospital of Soochow University
name: The Affiliated Hospital of Xuzhou Medical University
name: The Third Affiliated Hospital of Soochow University
name: Rugao People's Hospital
name: Nanfang Hospital, Southern Medical University
name: First Affiliated Hospital, Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Shantou Central Hospital
name: Meizhou People's Hospital
name: Changzhou Second People's Hospital affiliated with Nanjing Medical University
name: Zhangjiagang First People's Hospital
name: Huizhou Third People's Hospital, Guangzhou Medical University
First posted: 2024-02-05
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present study is a prospective, multicenter, non-inferiority, randomized controlled trail. It aims to investigate whether the efficacy of conduction system pacing (CSP) is non-inferior to biventricular pacing (BiVP) in patients with heart failure and right ventricular pacing (RVP) requiring upgrading to cardiac resynchronization therapy (CRT).

Detailed description: RVP is a standardized treatment strategy for severe bradyarrhythmia. However, RVP can result in electrical and mechanical dyssynchrony of the heart, which will adversely affect cardiac function. Until now, many studies have shown that RVP can promote the progression of heart failure, especially in patients with high ventricular pacing percentage. For these heart failure patients, upgrading to CRT is a feasible and effective therapy.

BiVP is a traditional method to achieve CRT, which can improve cardiac synchrony and provide great clinical outcomes for heart failure patients upgraded from RVP. CSP contains left bundle branch pacing (LBBP) and His bundle pacing (HBP), which is able to activate native His-Purkinje conduction system and solve the problems caused by RVP. Although HBP has high technical requirements, lower sense value and higher threshold, it is the pacing modality closest to physiological conditions so far. Since first reported by Huang et al. in 2017, LBBP has been carried out boomingly all over the world. LBBP has been reported to offer higher success rate with higher sense value and lower pacing thresholds compared with HBP, which can also achieve similar electrical and mechanical resynchronization as well as HBP.

However, no randomized controlled studies have been reported to compare the efficacy of CSP and BiVP in patients with heart failure and RVP requiring upgrading to CRT. CSP-UPGRADE is a non-inferiority study, and the purpose of which is to investigate whether the efficacy of CSP is not inferior to BiVP in such patients. Eligible patients will be 1:1 randomized to two groups. The primary outcome is change in LVEF between baseline and six months after device implantation assessed by echocardiography. According to BUDAPEST-CRT Upgrade trial, half of lower limit of the 95% confidence interval for difference in mean ΔLVEF between the CRTD and ICD group is about 3.8%, which is used as non-inferiority margin in the present study. Based on previous studies and cases, it is assumed that the mean ΔLVEF values in patients upgraded to CSP and BiVP are equal and the standard deviations are both 5%. With power as 80%, alpha as 0.025, rate of lost-of-follow-up as 10%, the final sample size was estimated as 66 by using PASS Version 21.0.3 (33 patients for each group). If the non-inferiority test reaches positive results, then we will further verify whether CSP is superior to BiVP in such patients.

Eligibility criteria: Inclusion Criteria:

1. Patients with symptomatic heart failure (LVEF \<50%) after right ventricular pacing for at least 3 months;
2. NYHA class II-IV;
3. NT-proBNP \>125pg/mL in patients with sinus rhythm, NT-proBNP \>250pg/mL in patients with atrial fibrillation;
4. Right ventricular pacing percentage \>40%;
5. Adult patients aged 18-80;
6. With informed consent signed.

Exclusion Criteria:

1. History of acute myocardial infarction within 3 months before enrollment;
2. Frequent premature ventricular contraction (\>15%) or malignant ventricular arrhythmia which is difficult to control;
3. History of valvular heart disease intervention within 3 months before enrollment;
4. After mechanical tricuspid valve replacement;
5. Ventricular septal hypertrophy (≥15mm during diastole);
6. Complex congenital heart disease;
7. History of heart transplantation;
8. Enrollment in any other study;
9. Pregnant or with child-bearing plan;
10. A life expectancy of less than 12 months.

Primary outcomes:
measure: ΔLVEF
timeFrame: Baseline; 6-month follow-up
Secondary outcomes:
measure: ΔLVEDD
timeFrame: Baseline; 3-month follow-up; 6-month follow-up
measure: ΔLVEDV
timeFrame: Baseline; 3-month follow-up; 6-month follow-up
measure: ΔLVESV
timeFrame: Baseline; 3-month follow-up; 6-month follow-up
measure: Paced QRS duration
timeFrame: 1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
measure: Echocardiographic response rate
timeFrame: Baseline; 6-month follow-up
measure: Changes in NT-proBNP
timeFrame: Baseline; 3-month follow-up; 6-month follow-up
measure: Changes in New York Heart Association Heart Function Classification
timeFrame: Baseline; 1-month follow-up; 3-month follow-up; 6-month follow-up
measure: Changes in 6-minute Walk Distance
timeFrame: Baseline; 3-month, 6-month follow-up
measure: Change in Quality Of Life Questionnaire score
timeFrame: Baseline; 3-month follow-up; 6-month follow-up
measure: Incidence of clinical adverse events
timeFrame: 1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
measure: Procedure-related costs
timeFrame: 1 day before discharge
measure: Estimated longevity of the device
timeFrame: 1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
measure: Pacing parameters
timeFrame: 1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
measure: Pacemaker related complications
timeFrame: 1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
References:
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. doi: 10.1093/eurheartj/ehac075.
citation: Chung MK, Patton KK, Lau CP, Dal Forno ARJ, Al-Khatib SM, Arora V, Birgersdotter-Green UM, Cha YM, Chung EH, Cronin EM, Curtis AB, Cygankiewicz I, Dandamudi G, Dubin AM, Ensch DP, Glotzer TV, Gold MR, Goldberger ZD, Gopinathannair R, Gorodeski EZ, Gutierrez A, Guzman JC, Huang W, Imrey PB, Indik JH, Karim S, Karpawich PP, Khaykin Y, Kiehl EL, Kron J, Kutyifa V, Link MS, Marine JE, Mullens W, Park SJ, Parkash R, Patete MF, Pathak RK, Perona CA, Rickard J, Schoenfeld MH, Seow SC, Shen WK, Shoda M, Singh JP, Slotwiner DJ, Sridhar ARM, Srivatsa UN, Stecker EC, Tanawuttiwat T, Tang WHW, Tapias CA, Tracy CM, Upadhyay GA, Varma N, Vernooy K, Vijayaraman P, Worsnick SA, Zareba W, Zeitler EP. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023 Sep;20(9):e17-e91. doi: 10.1016/j.hrthm.2023.03.1538. Epub 2023 May 20.
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.
citation: Kaye GC, Linker NJ, Marwick TH, Pollock L, Graham L, Pouliot E, Poloniecki J, Gammage M; Protect-Pace trial investigators. Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study. Eur Heart J. 2015 Apr 7;36(14):856-62. doi: 10.1093/eurheartj/ehu304. Epub 2014 Sep 4.
citation: Khurshid S, Obeng-Gyimah E, Supple GE, Schaller R, Lin D, Owens AT, Epstein AE, Dixit S, Marchlinski FE, Frankel DS. Reversal of Pacing-Induced Cardiomyopathy Following Cardiac Resynchronization Therapy. JACC Clin Electrophysiol. 2018 Feb;4(2):168-177. doi: 10.1016/j.jacep.2017.10.002. Epub 2017 Nov 15.
citation: Shan P, Su L, Zhou X, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA, Huang W. Beneficial effects of upgrading to His bundle pacing in chronically paced patients with left ventricular ejection fraction <50. Heart Rhythm. 2018 Mar;15(3):405-412. doi: 10.1016/j.hrthm.2017.10.031. Epub 2017 Nov 16.
citation: Qian Z, Wang Y, Hou X, Qiu Y, Wu H, Zhou W, Zou J. Efficacy of upgrading to left bundle branch pacing in patients with heart failure after right ventricular pacing. Pacing Clin Electrophysiol. 2021 Mar;44(3):472-480. doi: 10.1111/pace.14147. Epub 2021 Jan 31.
citation: Merkely B, Hatala R, Wranicz JK, Duray G, Foldesi C, Som Z, Nemeth M, Goscinska-Bis K, Geller L, Zima E, Osztheimer I, Molnar L, Karady J, Hindricks G, Goldenberg I, Klein H, Szigeti M, Solomon SD, Kutyifa V, Kovacs A, Kosztin A. Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial. Eur Heart J. 2023 Oct 21;44(40):4259-4269. doi: 10.1093/eurheartj/ehad591.