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Left vs Left Randomized Clinical Trial

Not Applicable
Recruiting
Conditions
AV Block
Heart Failure
Intraventricular Conduction Delay
LBBB
Heart Failure With Reduced Ejection Fraction
RBBB
Pacing-Induced Cardiomyopathy
Interventions
Device: BiVP
Device: His/LBBP
Registration Number
NCT05650658
Lead Sponsor
Baylor College of Medicine
Brief Summary

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2136
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Biventricular Pacing (BiVP)BiVPPatients with LVEF≤35% at entry will receive a BiV defibrillator which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular ICD lead, and and an epicardial left ventricular lead implanted in a branch of the coronary sinus. Patients with LVEF 36-50% at entry will receive BiV pacemaker which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular pacing lead, and and an epicardial left ventricular lead implanted in a branch of the coronary sinus.
His/Left Bundle Branch Pacing (His/LBBP)His/LBBPPatients with LVEF≤35% at entry will receive a His/LBB defibrillator which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular ICD lead, and an endocardial His-bundle or left bundle branch pacing lead directly pacing the intrinsic conduction system. Patients with LVEF 36-50% at entry will receive His/LBB pacemaker which includes implantation of two leads, an endocardial right atrial lead, and an endocardial His-bundle or left bundle branch pacing lead directly pacing the intrinsic conduction system.
Primary Outcome Measures
NameTimeMethod
A combined clinical endpoint of all-cause mortality and hospitalization for heart failure5.5 years

The primary efficacy outcome will be described using Kaplan-Meier freedom from event curves over time, with event-free survival compared between assigned treatment arms using a logrank test, stratified by levels of the two factors (LVEF (≤35% vs. 36 to 50%) and conduction abnormality (LBBB vs non-LBBB)) used for randomization.

Secondary Outcome Measures
NameTimeMethod
Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months12 months

Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) item score measured before and at 12 months after implant.

Change in composite endpoint comprised of death, first hospitalization for worsening HF and left ventricular end systolic volume index (LVESVi) at 5.5 years5.5 years

Secondary endpoint measured from all cause death, first hospitalization for heart failure and echocardiography on left ventricular end-systolic volume index (LVESVi) in the His/LBBP vs. BIV-BiVP arm

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 ratio5.5 years

Secondary endpoint measured from 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

Death from any cause at 5.5 years5.5 years

Secondary endpoint measured from all cause death

Death from any cardiovascular cause at 5.5 years5.5 years

Secondary endpoint measured from death due to cardiovascular causes

Hospitalization for heart failure at 5.5 years5.5 years

Secondary endpoint measured from first hospitalization for heart failure

Cardiovascular hospitalization at 5.5 years5.5 years

Secondary endpoint measured from first hospitalization for cardiovascular disease

Total HF hospitalizations5.5 years

Total number of HF hospitalizations

Composite of cardiovascular death or first HF hospitalization5.5 years

Secondary endpoint measured from cardiovascular death, first hospitalization for heart failure

Composite cardiovascular death or HF hospitalization or heart transplant or durable left ventricular assist device5.5 years

Secondary endpoint measured from cardiovascular death, heart transplant or durable left ventricular assist device

Change in NYHA Classification at 12 months12 months

Secondary endpoint measured from New York Heart Association class

Change in Six Minute Walk Test performance at 12 months12 months

Secondary endpoint measured from Six Minute Walk Test

Patient activity measured through cardiovascular implantable electronic devices (CIED) at 12 months12 months

Measurement Patient activity measured through cardiovascular implantable electronic devices (CIED)

Change in NT-proBNP at 12 months12 months

Measurement of heart failure serum biomarker NT-proBNP

Trial Locations

Locations (12)

Lovelace Medical Center

🇺🇸

Albuquerque, New Mexico, United States

Novant Health

🇺🇸

Charlotte, North Carolina, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Sentara Healthcare

🇺🇸

Newport News, Virginia, United States

University of Calgary

🇨🇦

Calgary, Canada

Waterloo Wellington Cardiovascular Research Institute (WWCRI) - St. Mary's General Hospital

🇨🇦

Kitchener, Canada

Research Institute of the McGill University Health Centre (RI-MUHC) - MUHC, Montreal General Hospital

🇨🇦

Montréal, Canada

Rush University

🇺🇸

Chicago, Illinois, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Geisinger Commonwealth School of Medicine

🇺🇸

Scranton, Pennsylvania, United States

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

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