Left vs Left Randomized Clinical Trial

Official title

Cardiac Resynchronization Therapy Using His/Left Bundle Branch Pacing vs Biventricular Pacing With a Left Ventricular Epicardial Lead in Patients With Heart Failure (HF) With Left Ventricular Ejection Fraction (LVEF)≤50% and With Either a Wide QRS Complex (>130 ms) or With/Anticipated >40% Pacing Randomized Clinical Trial

Overview

The investigators aim to prospectively test the comparative effectiveness of His or Left bundle branch pacing in relation to patient centered outcomes (quality of life, physical activity, heart failure hospitalization, mortality) and comparative safety in relation to device-related complications and re-interventions (e.g., lead dislodgement, infection) relative to standard of care biventricular pacing in patients with heart failure due to left ventricular systolic dysfunction (LVEF≤50%) and with either a wide QRS (≥130 ms) or with/anticipated \>40% pacing who are already receiving current standard heart failure pharmacological therapy.

Detailed description

In this prospective, randomized, multi-center clinical trial, the investigators aim to prospectively evaluate the comparative effectiveness His or Left bundle branch pacing (His/LBBP) vs. biventricular pacing (BiVP) in patients with heart failure due to left ventricular systolic dysfunction (LVEF≤50%) and with either a wide QRS (≥130 ms) or with/anticipated \>40% pacing who are already receiving current standard heart failure pharmacological therapy by assessing all cause death and heart failure hospitalization at the end of the study.

Additional formal secondary objectives include evaluation disease-specific quality and psychological adjustment changes at 1 year after device implant and evaluation of a composite of death of any cause or heart failure hospitalization or more \>15% increase in the left ventricular end-systolic volume index at the end of the study.

Interventions

• Device His/LBBP
  Pacing at the level His-Bundle or left bundle branch is used to correct the underlying conduction abnormality, resulting in a faster and more homogeneous activation of the heart pacing directly via the intrinsic conduction system of the heart accompanied by a right atrial endocardial lead and a right ventricular defibrillator endocardial lead for LVEF≤35% and by a right atrial endocardial lead for LVEF 36-50%.
• Device BiVP
  Biventricular pacing has been shown to improve outcomes by delivering synchronized electrical stimuli to the right and left ventricles utilizing an an endocardial right atrial lead, an endocardial right ventricular lead, and an epicardial left ventricular lead implanted in a branch of the coronary sinus. For LVEF≤35% a biventricular pacemaker-defibrillator will be implanted while for LVEF 36-50% a biventricular pacemaker will be implanted.

Primary outcome measures

• A combined clinical endpoint of all-cause mortality and hospitalization for heart failure [Time frame: 5.5 years]

Secondary outcome measures (12)

• Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months [Time frame: 12 months]
• Change in composite endpoint comprised of death, first hospitalization for worsening HF and left ventricular end systolic volume index (LVESVi) at 5.5 years [Time frame: 5.5 years]
• Composite of cardiovascular death or heart transplant or durable left ventricular assist device or more > 15% increase in the LVESVi or change in KCCQ-12 at the end of the study using win ratio [Time frame: 5.5 years]
• Death from any cause at 5.5 years [Time frame: 5.5 years]
• Death from any cardiovascular cause at 5.5 years [Time frame: 5.5 years]
• Hospitalization for heart failure at 5.5 years [Time frame: 5.5 years]
• Cardiovascular hospitalization at 5.5 years [Time frame: 5.5 years]
• Total HF hospitalizations [Time frame: 5.5 years]
• Composite of cardiovascular death or first HF hospitalization [Time frame: 5.5 years]
• Composite cardiovascular death or HF hospitalization or heart transplant or durable left ventricular assist device [Time frame: 5.5 years]
• Change in NYHA Classification at 12 months [Time frame: 12 months]
• Change in Six Minute Walk Test performance at 12 months [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Men and women 18 years of age or older.
• A LVEF ≤ 50% within 6 months prior to enrollment.
• Resting QRS duration ≥130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR anticipated right ventricular pacing >40% OR device in place with right ventricular pacing > 40%.
• Are optimized on HF guideline directed medical therapy according to current HF published guidelines OR patient's physician will make an effort to start all guideline-directed medical therapy and titrate doses up as permitted by the participant clinical status and co-morbidities prior to implantation procedure.

Exclusion criteria

• Women who are pregnant, lactating, or plan to become pregnant during the course of the trial.
• Participants with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary, intervention in the next three (3) months.
• Enzyme-positive myocardial infarction within the past three (3) months prior to enrollment.
• Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past three (3) months prior to enrollment.
• Reversible non-ischemic cardiomyopathy (e.g., acute viral myocarditis).
• Participants with Chagas disease, cardiac sarcoidosis or amyloidosis.
• Expected to receive left ventricular assist device or heart transplantation within 6 months.
• Participants with primary severe valvular disease (e.g., aortic stenosis).
• Have a life expectancy of less than 12 months.
• Participants with irreversible brain damage from preexisting cerebral disease.
• Participants with a contrast dye allergy unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine.
• Participants participating in any other interventional cardiovascular clinical trial.
• Participants who would be unable to comply with the study's follow-up visit schedule; or
• Participants who had any prior unsuccessful attempt at implantation of biventricular pacing (BiVP), His Bundle Pacing (HBP), or Left Bundle Branch Pacing (LBBP) device.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 57 centers

• Mercy Gilbert & Chandler Regional Medical Centers, Gilbert AZ — Gilbert
• University of Arizona College of Medicine- Phoenix — Tucson
• University of Arkansas for Medical Sciences (UAMS) — Little Rock
• University of California San Diego — La Jolla
• University of Colorado (Anschutz Medical Campus) — Denver
• South Denver Cardiology Associates — Littleton
• Hartford Hospital — Hartford
• Yale University — New Haven
• … and 49 more centers

Canada · 14 centers

• Mazankowski Alberta Heart Institute/University of Alberta — Edmonton
• University of British Columbia — Vancouver
• Victoria Cardiac Arrhythmia Trials (VCAT) Inc. — Victoria
• Nova Scotia Health Authority — Halifax
• Hamilton Health Sciences (HHS) — Hamilton
• Newmarket Electrophysiology Research Group Inc. (NERG) — Newmarket
• University of Ottawa Heart Institute — Ottawa
• Sunnybrook Research Institute — Toronto
• … and 6 more centers

Publications

• Abe TA, Evbayekha EO, Jackson LR 2nd, Al-Khatib SM, Lewsey SC, Breathett K. Evolving Indications, Challenges and Advances in Cardiac Resynchronization Therapy for Heart Failure. J Card Fail. 2026 Feb;32(2):499-514. doi: 10.1016/j.cardfail.2025.01.031. Epub 2025 Apr 16. PMID 40250827
• Infeld M, Cyr JA, Sanchez-Quintana D, Madias C, Udelson JE, Lustgarten DL, Meyer M. Physiological Pacing for the Prevention and Treatment of Heart Failure: a State-of-the-Art Review. J Card Fail. 2024 Dec;30(12):1614-1628. doi: 10.1016/j.cardfail.2024.08.063. Epub 2024 Oct 29. PMID 39481799

Identifiers

NCT: NCT05650658 · PLACER 2021C3- 24160

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗