Non-ischemic CardiomyopathyLIT-HFNCT05572957
LBBP as Initial Therapy in Patients With Non-ischemic Heart Failure and LBBB
A study testing Guideline-Directed Medical Therapy(GDMT) and left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT) in people with Non-ischemic Cardiomyopathy and Heart Failure, run by The First Affiliated Hospital with Nanjing Medical University at 6 sites in China.
Trial summary
The present study will recruit 50 symptomatic non-ischemic cardiomyopathy (NICM) patients with left ventricular ejection fraction (LVEF) below 35% and complete left bundle branch block (CLBBB), who have not received complete guideline-directed medical therapy (GDMT). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-ischemic Cardiomyopathy, Heart Failure, Left Bundle-Branch Block
- What is being tested?
- Guideline-Directed Medical Therapy(GDMT) and left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesChina
- Study dates
- 14 Oct 2022to Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-ischemic cardiomyopathy with LVEF≤35% as assessed by echocardiography, NYHA class II-III, and less than 3 months of optimized (complete) GDMT*;
- Sinus rhythm (paroxysmal atrial fibrillation may be present) with complete left bundle branch block meeting STRAUSS's criteria;
- Between the ages of 18 and 80;
- With informed consent signed.
Who cannot join
- After mechanical tricuspid valve replacement;
- Ischemic cardiomyopathy;
- Persistent AF without AV node ablation;
- History of unexplained syncope or indications for pacemaker implantation;
- Indications for ICD implantation such as a history of sustained ventricular tachycardia or sudden cardiac arrest;
- Unstable angina, acute MI, CABG or PCI within the past 3 months;
Show all 10Show fewer
- Enrollment in any other study；
- A life expectancy of less than 12 months;
- Pregnant or with child-bearing potential;
- History of heart transplantation.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites
Fuwai Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality
West China Hospital, Sichuan University
Chengdu, Sichuan
The First Affiliated Hospital of Dalian Medical University
Dalian, Liaoning
Fujian Medical University Union Hospital
Fuzhou, Fujian
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, 210029
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang
About this study
Official title: Left Bundle Branch Pacing as Initial Therapy in Patients With Non-ischemic Heart Failure and Left Bundle Branch Block (LIT-HF Study)
The present study will recruit 50 symptomatic non-ischemic cardiomyopathy (NICM) patients with left ventricular ejection fraction (LVEF) below 35% and complete left bundle branch block (CLBBB), who have not received complete guideline-directed medical therapy (GDMT). Each patient was randomized to 2 groups, GDMT or left bundle branch pacing combined with GDMT (LBBP+GDMT) as initial therapy and was followed up for 2 phases: 0-6 months (phase I), 7-18 months (phase II). The primary objective is to compare the LVEF change , syncope and malignant ventricular arrhythmias between GDMT group and LBBP+GDMT group, and to observe which strategy will significantly reduce the percentage of recommendations for an implantable cardioverter-defibrillator (ICD) during phase I study. The second outcome measures including health economics, echocardiography parameters[left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV)], N-terminal pro B-type natriuretic peptide (NT-proBNP) level, New York Heart Association (NYHA) class, 6-minute walking distance (6MWD), quality of life score(QOL) and incidence of clinical adverse events.
Read the detailed description
Therapies currently approved to treat heart failure with reduced ejection fraction (HFrEF) have generally shown significant benefit on morbidity and mortality, resulting in strong recommendations in treatment guidelines. Four standard drugs classes, composed of beta-blockers, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor (ACE-I/ARB/ARNI), mineralocorticoid receptor antagonist (MRA) and sodium-glucose co-transporter 2 inhibitor (SGLT2i), have already been standard background therapy in HFrEF. Cardiac resynchronization therapy with pacemaker/Cardiac resynchronization therapy with defibrillation (CRT-P/CRT-D) is an established treatment to HF patients, especially in LVEF ≤35%, sinus rhythm, CLBBB with a QRS duration (QRSd) ≥150 ms, and symptoms on 3-6 months of GDMT. Both the 2021 ESC and the 2022 AHA/ACC/HFSA guidelines for HF included LVEF≤35% after 3-6 months of GDMT as a strong indication for ICD implantation in non-ischemic heart disease.
The traditional biventricular pacing (BiVP) could correct the cardiac dyssynchrony to improve clinical symptoms and reduce all-cause mortality in HF. However, almost 30%-40% of patients with successful implantation show no response and BiVP just corrects the mechanical dyssynchrony caused by LBBB not corrects the LBBB. His Purkinje conduction system pacing (HPCSP) technology has made significant progress in recent five years. His bundle pacing (HBP) and left bundle branch pacing(LBBP) can correct LBBB and achieve physiological cardiac resynchronization only by ordinary single-chamber or dual-chamber pacemaker. LBBP has been reported to produce stable pacing thresholds, adequately sensed R-wave amplitude, and higher likelihood to correct LBBB by pacing more distal to the site of conduction block compared with HBP. The feasibility and efficacy of LBBP for CRT in HF patients with LBBB was demonstrated by previous observational studies showing that LBBP-CRT achieves a narrower QRSd, higher percentage of super responders, and lower pacing thresholds than BiVP-CRT. The LBBP-RESYNC study showed that LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in HF patients with NICM and LBBB.
It remains unclear as to the following questions: 1. After 3-6 months of GDMT, what is the percentage of patients with LVEFs improvement from ≤35% to >35% in HFrEF patients with NICM and CLBBB, and what are the absolute values of the increase in LVEFs; 2. How is the long-term prognosis of those patients with LVEF increased to >35% after GDMT. Whether these patients still need an ICD/CRT-D since they do not fall within the recommendations for primary prevention of sudden cardiac death (SCD); 3. What are the differences of LVEFs changes if LBBP is added to the medical treatment at the beginning.
There are to date no randomized studies comparing GDMT and LBBP combined with GDMT (LBBP+GDMT) as the initial therapy in HFrEF patients with NICM and CLBBB. The purpose of this study is to compare the therapeutic effects of LBBP+GDMT and GDMT on LV function and clinical endpoints in such patients. The present study will randomize about 50 patients in multiple centres to LBBP+GDMT group or GDMT group.
The study is divided into two phases:
Phase I (0-6 months) : Patients are randomly assigned to either the drug therapy group (GDMT group) or the experimental group (LBBP+GDMT group). In GDMT group at 3-month follow-up, CRT-P/CRT-D will be implanted if LVEF is still ≤35% with absolute increase <5% from baseline or ventricular tachycardia/ventricular fibrillation (VT/VF) events are recorded; otherwise, GDMT will be continued when LVEF >35% or LVEF≤35% but absolute increase >5% from baseline and no VT/VF event is observed. Patients in LBBP+GDMT group are directly treated with LBBP and GDMT after enrollment. The proportions of patients with LVEF ≤35% or VT/VF events in LBBP+GDMT group are assessed at 3-month and 6-month. The percentages of patients with LVEF ≤35% or VT/VF events in GDMT group are also assessed after 3 and 6 months as well.
Phase II (7-18 months): Patients in each group are followed up regularly (every 3-6 months, with mandatory at 12 and 18 months, with additional as appropriate) to assess the need for CRT-P/CRT-D/ICD when EF decreasing to ≤35%, syncope, or VT/VF events occurred.
- Being tested
- Guideline-Directed Medical Therapy(GDMT), left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)
- Keywords
- Non-ischemic Cardiomyopathy, Heart Failure, Left Bundle-Branch Block, Guideline-Directed Medical Therapy, Left Bundle Branch Pacing, Implantable Cardioverter-Defibrillator, Cardiac Resynchronization Therapy
- Medical subject headings
- Heart Failure, Bundle-Branch Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Guideline-Directed Medical Therapy(GDMT)Drug
Also called Optimal Medical Therapy(OMT)
Quadruple anti-heart failure drug therapy: BB, ACEI/ARB/ARNI, MRA, and SGLT2i. If the initial dose according to guidelines is tolerated, the protocol would then direct the uptitration of medication dose over time to a specified target dose, unless not well tolerated.
*Criteria for <3 months of optimized (complete) GDMT: 1) according to the latest management of HF, any of the "new quadruple therapy" is not used if the condition allowed; Or 2) the dose of any drug dose not reach the maximum tolerated target; Or 3) under the maximum tolerated dose of BB, ivabradine is not added with a heart rate still ≥70 bpm at rest.
left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)Combination product
GDMT is the same as Drug intervention. LBBP is confirmed when: 1) the LBBB morphology disappeared and the paced RBBB pattern (typical or atypical) is observed in V1; and 2) LVAT is ≤100 ms at low output(≤3 V/0.5 ms); and at least 1 of the following is achieved: a) abrupt shortening of LVAT by >10 ms during mid/deep septal lead placement with a RBBB pattern in V1 at high output, which then remains short and constant at high and low output with further advancement of the lead to the final position; b) transition from nonselective to selective LBBP (QRS morphology transition from atypical RBBB to typical rsR' pattern in V1 and wide/large S-wave in V6 , with the appearance of an isoelectric segment and no LVAT change at high and low outputs); and c) transition from nonselective LBBP to LV septal pacing (lengthening of LVAT by at least 10 ms with or without obvious QRS morphology transition during threshold testing).
HBP or BiVP is attempted using the standard-of-care technique.
| Study group | Role | What they receive |
|---|---|---|
| GDMT group | Active comparator | With the current guidelines of recommended therapies for HF, each patient who meets the inclusion criteria should begin being on all 4 drug classes after enrollment, including a beta-blocker (BB), a RAS inhibitor (ACEI, ARB) or ARNI (preferred), an MRA, and an SGLT2i.
The appeal drugs should be gradually uptitrated to the maximum tolerated dose within the first 3-6 months.
Ivabradine will be added to the patients whose resting heart rates remain above 70 beats per minute (bpm) after adequate medical treatment, including a BB at maximum tolerated dose. Receives: Drug: Guideline-Directed Medical Therapy(GDMT) |
| LBBP+GDMT group | Experimental | In this arm, medications are the same as the GDMT group. The LBBP lead is introduced into the right ventricle (RV) and is placed on the right side of the interventricular septum (IVS). The lead is advanced deeply into the IVS until reaching the LV septal subendocardium and right bundle branch block (RBBB) morphology of the paced QRS complex is observed in electrocardiogram (ECG) lead V1.
If LBBP fails, his bundle pacing (HBP) should be considered when HBP could correct LBBB.
If both of LBBP and HBP fail, conventional BiVP-CRT could be the last option. Receives: Combination Product: left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD)
After treatment with two strategies(GDMT, LBBP+GDMT), the percentages of LVEF still ≤35% and/or ventricular arrhythmia events was assessed in both groups. That is, the percentage of patients who are eligible for primary/secondary prevention ICD implantation.
Measured: 6-month follow-up
Secondary outcomes (8)
Health economics
The cost of the two treatment strategies were evaluated comprehensively, including each inpatient, outpatient and unplanned follow-up
Measured: 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVEF
LVEF is assessed by echocardiography (Simpson's rule) and compared between the baseline and follow-up.
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVESV
LVESV is assessed by echocardiography (Simpson's rule) and compared between the baseline and follow-up.
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVEDV
LVEDV is assessed by echocardiography (Simpson's rule) and compared between the baseline and follow-up.
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in concentration of NT-proBNP in blood between baseline and follow-up
Blood test is performed at each time frame to determine the concentration of NT-proBNP(unit: pg/mL)
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in New York Heart Association Heart Function Classification between baseline and follow-up
The higher the classification, the more severe the heart failure symptoms(four levels: I, II, III and IV)
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Change in Quality Of Life Questionnaire score between baseline and follow-up
Reflect the effect of heart failure on quality of life, and higher scores represent a worse outcome
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Incidence of clinical adverse events
Including date and number of all-cause mortality, heart failure hospitalization, cardiovascular hospitalization and malignant ventricular arrhythmia
Measured: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start14 Oct 2022
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Non-ischemic CardiomyopathyStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The First Affiliated Hospital of Dalian Medical University, West China Hospital, First Affiliated Hospital of Wenzhou Medical University, Fujian Medical University Union Hospital, Chinese Academy of Medical Sciences, Fuwai Hospital
- Responsible party
- Sponsor
- Investigators
- Jiangang Zou, MD,Ph.D, Principal investigator, First Affiliated Hospital, Nanjing Medical UniversityXiaofeng Hou, MD, Principal investigator, First Affiliated Hospital, Nanjing Medical UniversityYunlong Xia, MD, Principal investigator, The First Affiliated Hospital of Dalian Medical UniversityYingxue Dong, MD, Principal investigator, The First Affiliated Hospital of Dalian Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05572957
- Sponsor's protocol ID
- FirstNanjingMU004
- Acronym
- LIT-HF
- Status last verified
- May 2026
- First submitted
- 6 Oct 2022
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol. 2017 Dec;33(12):1736.e1-1736.e3. doi: 10.1016/j.cjca.2017.09.013. Epub 2017 Sep 22.
PubMed 29173611Wang Y, Zhu H, Hou X, Wang Z, Zou F, Qian Z, Wei Y, Wang X, Zhang L, Li X, Liu Z, Xue S, Qin C, Zeng J, Li H, Wu H, Ma H, Ellenbogen KA, Gold MR, Fan X, Zou J; LBBP-RESYNC Investigators. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2022 Sep 27;80(13):1205-1216. doi: 10.1016/j.jacc.2022.07.019.
PubMed 36137670Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.
PubMed 31096064McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
PubMed 34447992Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
PubMed 35363499
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Left Bundle Branch Pacing as Initial Therapy in Patients With Non-ischemic Heart Failure and Left Bundle Branch Block (LIT-HF Study)
- ClinicalTrials.gov ID
- NCT05572957
- Acronym / sponsor ID
- LIT-HF / FirstNanjingMU004
- Keywords
- Non-ischemic Cardiomyopathy, Heart Failure, Left Bundle-Branch Block, Guideline-Directed Medical Therapy, Left Bundle Branch Pacing, Implantable Cardioverter-Defibrillator, Cardiac Resynchronization Therapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- The First Affiliated Hospital of Dalian Medical University, West China Hospital, First Affiliated Hospital of Wenzhou Medical University, Fujian Medical University Union Hospital, Chinese Academy of Medical Sciences, Fuwai Hospital
- Study start
- 14 Oct 2022 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 10 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study will recruit 50 symptomatic non-ischemic cardiomyopathy (NICM) patients with left ventricular ejection fraction (LVEF) below 35% and complete left bundle branch block (CLBBB), who have not received complete guideline-directed medical therapy (GDMT). Each patient was randomized to 2 groups, GDMT or left bundle branch pacing combined with GDMT (LBBP+GDMT) as initial therapy and was followed up for 2 phases: 0-6 months (phase I), 7-18 months (phase II). The primary objective is to compare the LVEF change , syncope and malignant ventricular arrhythmias between GDMT group and LBBP+GDMT group, and to observe which strategy will significantly reduce the percentage of recommendations for an implantable cardioverter-defibrillator (ICD) during phase I study. The second outcome measures including health economics, echocardiography parameters[left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV)], N-terminal pro B-type natriuretic peptide (NT-proBNP) level, New York Heart Association (NYHA) class, 6-minute walking distance (6MWD), quality of life score(QOL) and incidence of clinical adverse events.
Detailed description
Therapies currently approved to treat heart failure with reduced ejection fraction (HFrEF) have generally shown significant benefit on morbidity and mortality, resulting in strong recommendations in treatment guidelines. Four standard drugs classes, composed of beta-blockers, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor (ACE-I/ARB/ARNI), mineralocorticoid receptor antagonist (MRA) and sodium-glucose co-transporter 2 inhibitor (SGLT2i), have already been standard background therapy in HFrEF. Cardiac resynchronization therapy with pacemaker/Cardiac resynchronization therapy with defibrillation (CRT-P/CRT-D) is an established treatment to HF patients, especially in LVEF ≤35%, sinus rhythm, CLBBB with a QRS duration (QRSd) ≥150 ms, and symptoms on 3-6 months of GDMT. Both the 2021 ESC and the 2022 AHA/ACC/HFSA guidelines for HF included LVEF≤35% after 3-6 months of GDMT as a strong indication for ICD implantation in non-ischemic heart disease.
The traditional biventricular pacing (BiVP) could correct the cardiac dyssynchrony to improve clinical symptoms and reduce all-cause mortality in HF. However, almost 30%-40% of patients with successful implantation show no response and BiVP just corrects the mechanical dyssynchrony caused by LBBB not corrects the LBBB. His Purkinje conduction system pacing (HPCSP) technology has made significant progress in recent five years. His bundle pacing (HBP) and left bundle branch pacing(LBBP) can correct LBBB and achieve physiological cardiac resynchronization only by ordinary single-chamber or dual-chamber pacemaker. LBBP has been reported to produce stable pacing thresholds, adequately sensed R-wave amplitude, and higher likelihood to correct LBBB by pacing more distal to the site of conduction block compared with HBP. The feasibility and efficacy of LBBP for CRT in HF patients with LBBB was demonstrated by previous observational studies showing that LBBP-CRT achieves a narrower QRSd, higher percentage of super responders, and lower pacing thresholds than BiVP-CRT. The LBBP-RESYNC study showed that LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in HF patients with NICM and LBBB.
It remains unclear as to the following questions: 1. After 3-6 months of GDMT, what is the percentage of patients with LVEFs improvement from ≤35% to >35% in HFrEF patients with NICM and CLBBB, and what are the absolute values of the increase in LVEFs; 2. How is the long-term prognosis of those patients with LVEF increased to >35% after GDMT. Whether these patients still need an ICD/CRT-D since they do not fall within the recommendations for primary prevention of sudden cardiac death (SCD); 3. What are the differences of LVEFs changes if LBBP is added to the medical treatment at the beginning.
There are to date no randomized studies comparing GDMT and LBBP combined with GDMT (LBBP+GDMT) as the initial therapy in HFrEF patients with NICM and CLBBB. The purpose of this study is to compare the therapeutic effects of LBBP+GDMT and GDMT on LV function and clinical endpoints in such patients. The present study will randomize about 50 patients in multiple centres to LBBP+GDMT group or GDMT group.
The study is divided into two phases:
Phase I (0-6 months) : Patients are randomly assigned to either the drug therapy group (GDMT group) or the experimental group (LBBP+GDMT group). In GDMT group at 3-month follow-up, CRT-P/CRT-D will be implanted if LVEF is still ≤35% with absolute increase <5% from baseline or ventricular tachycardia/ventricular fibrillation (VT/VF) events are recorded; otherwise, GDMT will be continued when LVEF >35% or LVEF≤35% but absolute increase >5% from baseline and no VT/VF event is observed. Patients in LBBP+GDMT group are directly treated with LBBP and GDMT after enrollment. The proportions of patients with LVEF ≤35% or VT/VF events in LBBP+GDMT group are assessed at 3-month and 6-month. The percentages of patients with LVEF ≤35% or VT/VF events in GDMT group are also assessed after 3 and 6 months as well.
Phase II (7-18 months): Patients in each group are followed up regularly (every 3-6 months, with mandatory at 12 and 18 months, with additional as appropriate) to assess the need for CRT-P/CRT-D/ICD when EF decreasing to ≤35%, syncope, or VT/VF events occurred.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GDMT group | Active comparator | Drug: Guideline-Directed Medical Therapy(GDMT)With the current guidelines of recommended therapies for HF, each patient who meets the inclusion criteria should begin being on all 4 drug classes after enrollment, including a beta-blocker (BB), a RAS inhibitor (ACEI, ARB) or ARNI (preferred), an MRA, and an SGLT2i. The appeal drugs should be gradually uptitrated to the maximum tolerated dose within the first 3-6 months. Ivabradine will be added to the patients whose resting heart rates remain above 70 beats per minute (bpm) after adequate medical treatment, including a BB at maximum tolerated dose. |
| LBBP+GDMT group | Experimental | Combination Product: left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)In this arm, medications are the same as the GDMT group. The LBBP lead is introduced into the right ventricle (RV) and is placed on the right side of the interventricular septum (IVS). The lead is advanced deeply into the IVS until reaching the LV septal subendocardium and right bundle branch block (RBBB) morphology of the paced QRS complex is observed in electrocardiogram (ECG) lead V1. If LBBP fails, his bundle pacing (HBP) should be considered when HBP could correct LBBB. If both of LBBP and HBP fail, conventional BiVP-CRT could be the last option. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Non-ischemic cardiomyopathy with LVEF≤35% as assessed by echocardiography, NYHA class II-III, and less than 3 months of optimized (complete) GDMT*;
- Sinus rhythm (paroxysmal atrial fibrillation may be present) with complete left bundle branch block meeting STRAUSS's criteria;
- Between the ages of 18 and 80;
- With informed consent signed.
Key exclusion criteria (10 listed)
- After mechanical tricuspid valve replacement;
- Ischemic cardiomyopathy;
- Persistent AF without AV node ablation;
- History of unexplained syncope or indications for pacemaker implantation;
- Indications for ICD implantation such as a history of sustained ventricular tachycardia or sudden cardiac arrest;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Guideline-Directed Medical Therapy(GDMT)Also: Optimal Medical Therapy(OMT)Quadruple anti-heart failure drug therapy: BB, ACEI/ARB/ARNI, MRA, and SGLT2i. If the initial dose according to guidelines is tolerated, the protocol would then direct the uptitration of medication dose over time to a specified target dose, unless not well tolerated. *Criteria for <3 months of optimized (complete) GDMT: 1) according to the latest management of HF, any of the "new quadruple therapy" is not used if the condition allowed; Or 2) the dose of any drug dose not reach the maximum tolerated target; Or 3) under the maximum tolerated dose of BB, ivabradine is not added with a heart rate still ≥70 bpm at rest. | Drug | GDMT group |
| left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT)GDMT is the same as Drug intervention. LBBP is confirmed when: 1) the LBBB morphology disappeared and the paced RBBB pattern (typical or atypical) is observed in V1; and 2) LVAT is ≤100 ms at low output(≤3 V/0.5 ms); and at least 1 of the following is achieved: a) abrupt shortening of LVAT by >10 ms during mid/deep septal lead placement with a RBBB pattern in V1 at high output, which then remains short and constant at high and low output with further advancement of the lead to the final position; b) transition from nonselective to selective LBBP (QRS morphology transition from atypical RBBB to typical rsR' pattern in V1 and wide/large S-wave in V6 , with the appearance of an isoelectric segment and no LVAT change at high and low outputs); and c) transition from nonselective LBBP to LV septal pacing (lengthening of LVAT by at least 10 ms with or without obvious QRS morphology transition during threshold testing). HBP or BiVP is attempted using the standard-of-care technique. | Combination product | LBBP+GDMT group |
Primary outcome
Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD)
Time frame: 6-month follow-up
After treatment with two strategies(GDMT, LBBP+GDMT), the percentages of LVEF still ≤35% and/or ventricular arrhythmia events was assessed in both groups. That is, the percentage of patients who are eligible for primary/secondary prevention ICD implantation.
8 secondary outcomes
Health economics
Time frame: 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVEF
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVESV
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in LVEDV
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in concentration of NT-proBNP in blood between baseline and follow-up
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Changes in New York Heart Association Heart Function Classification between baseline and follow-up
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Change in Quality Of Life Questionnaire score between baseline and follow-up
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Incidence of clinical adverse events
Time frame: Baseline; 3-month, 6-month, 12-month, and 18-month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Background: PubMed 29173611Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol. 2017 Dec;33(12):1736.e1-1736.e3. doi: 10.1016/j.cjca.2017.09.013. Epub 2017 Sep 22.
- Background: PubMed 36137670Wang Y, Zhu H, Hou X, Wang Z, Zou F, Qian Z, Wei Y, Wang X, Zhang L, Li X, Liu Z, Xue S, Qin C, Zeng J, Li H, Wu H, Ma H, Ellenbogen KA, Gold MR, Fan X, Zou J; LBBP-RESYNC Investigators. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2022 Sep 27;80(13):1205-1216. doi: 10.1016/j.jacc.2022.07.019.
- Background: PubMed 31096064Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.
- Background: PubMed 34447992McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
- Background: PubMed 35363499Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiangang Zou, MD,Ph.D principal investigator
First Affiliated Hospital, Nanjing Medical University
Xiaofeng Hou, MD principal investigator
First Affiliated Hospital, Nanjing Medical University
Yunlong Xia, MD principal investigator
The First Affiliated Hospital of Dalian Medical University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Guideline-Directed Medical Therapy(GDMT) and left bundle branch pacing combined with Guideline-Directed Medical Therapy(LBBP+GDMT) in people with Non-ischemic Cardiomyopathy and Heart Failure, run by The First Affiliated Hospital with Nanjing Medical University at 6 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients requiring ICD implantation for prevention of sudden cardiac death(SCD) (time frame: 6-month follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05572957, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.