Clinical trial NCT05650658: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Heart Failure With Reduced Ejection Fraction
AV Block
LBBB
RBBB
Intraventricular Conduction Delay
Pacing-Induced Cardiomyopathy
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: University of Utah
name: Virginia Commonwealth University
name: Cleveland Clinic Florida
name: East Carolina University
First posted: 2022-12-14
Enrollment: 2136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: A combined clinical endpoint of all-cause mortality and hospitalization for heart failure
timeFrame: 5.5 years
Secondary outcomes:
measure: Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months
timeFrame: 12 months
measure: Change in composite endpoint comprised of death, first hospitalization for worsening HF and left ventricular end systolic volume index (LVESVi) at 5.5 years
timeFrame: 5.5 years
measure: 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
timeFrame: 5.5 years
measure: Death from any cause at 5.5 years
timeFrame: 5.5 years
measure: Death from any cardiovascular cause at 5.5 years
timeFrame: 5.5 years
measure: Hospitalization for heart failure at 5.5 years
timeFrame: 5.5 years
measure: Cardiovascular hospitalization at 5.5 years
timeFrame: 5.5 years
measure: Total HF hospitalizations
timeFrame: 5.5 years
measure: Composite of cardiovascular death or first HF hospitalization
timeFrame: 5.5 years
measure: Composite cardiovascular death or HF hospitalization or heart transplant or durable left ventricular assist device
timeFrame: 5.5 years
measure: Change in NYHA Classification at 12 months
timeFrame: 12 months
measure: Change in Six Minute Walk Test performance at 12 months
timeFrame: 12 months
measure: Patient activity measured through cardiovascular implantable electronic devices (CIED) at 12 months
timeFrame: 12 months
measure: Change in NT-proBNP at 12 months
timeFrame: 12 months
Other outcomes:
measure: Appropriate ICD therapy for ventricular arrhythmias
timeFrame: 5.5 years
measure: Incidence of atrial tachyarrhythmia events
timeFrame: 5.5 years
measure: Change in Left Ventricular Ejection Fraction (LVEF) at 12 months
timeFrame: 12 months
Locations:
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Albuquerque
country: United States
facility: Lovelace Medical Center
state: New Mexico
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Scranton
country: United States
facility: Geisinger Commonwealth School of Medicine
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Newport News
country: United States
facility: Sentara Healthcare
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary
city: Kitchener
country: Canada
facility: Waterloo Wellington Cardiovascular Research Institute (WWCRI) - St. Mary's General Hospital
city: Montréal
country: Canada
facility: Research Institute of the McGill University Health Centre (RI-MUHC) - MUHC, Montreal General Hospital
Study officials:
affiliation: Baylor College of Medicine
name: Mihail G Chelu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University
name: Kenneth A Ellenbogen, MD
role: PRINCIPAL_INVESTIGATOR
References: