Back to resultsLeft vs Left Randomized Clinical Trial
Primary Purpose
Heart Failure, Heart Failure With Reduced Ejection Fraction, AV Block
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
His/LBBP
BiVP
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
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. 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 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 return for follow-up visits due to the distance from the clinic. Participants who do not anticipate being a resident of the area for the scheduled duration of the trial.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
His/Left Bundle Branch Pacing (His/LBBP)
Biventricular Pacing (BiVP)
Arm Description
Patients 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.
Patients 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.
Outcomes
Primary Outcome Measures
A combined clinical endpoint of all-cause mortality and hospitalization for heart failure
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
Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 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 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
Death from any cause at 5.5 years
Secondary endpoint measured from all cause death
Death from any cardiovascular cause at 5.5 years
Secondary endpoint measured from death due to cardiovascular causes
Hospitalization for heart failure at 5.5 years
Secondary endpoint measured from first hospitalization for heart failure
Cardiovascular hospitalization at 5.5 years
Secondary endpoint measured from first hospitalization for cardiovascular disease
Change in NYHA Classification at 12 months
Secondary endpoint measured from New York Heart Association class
Change in Six Minute Walk Test performance at 12 months
Secondary endpoint measured from Six Minute Walk Test
Full Information
NCT ID
NCT05650658
First Posted
November 24, 2022
Last Updated
February 7, 2023
Sponsor
Baylor College of Medicine
Collaborators
Patient-Centered Outcomes Research Institute, University of Utah, Virginia Commonwealth University, Rush University, East Carolina University
1. Study Identification
Unique Protocol Identification Number
NCT05650658
Brief Title
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
June 30, 2029 (Anticipated)
Study Completion Date
June 30, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
Patient-Centered Outcomes Research Institute, University of Utah, Virginia Commonwealth University, Rush University, East Carolina University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Heart Failure With Reduced Ejection Fraction, AV Block, LBBB, RBBB, Intraventricular Conduction Delay, Pacing-Induced Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
2136 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
His/Left Bundle Branch Pacing (His/LBBP)
Arm Type
Active Comparator
Arm Description
Patients 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.
Arm Title
Biventricular Pacing (BiVP)
Arm Type
Active Comparator
Arm Description
Patients 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.
Intervention Type
Device
Intervention Name(s)
His/LBBP
Intervention Description
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%.
Intervention Type
Device
Intervention Name(s)
BiVP
Intervention Description
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 Measure Information:
Title
A combined clinical endpoint of all-cause mortality and hospitalization for heart failure
Description
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.
Time Frame
5.5 years
Secondary Outcome Measure Information:
Title
Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months
Description
Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) item score measured before and at 12 months after implant.
Time Frame
12 months
Title
Change in composite endpoint comprised of death, first hospitalization for worsening HF and left ventricular end systolic volume index (LVESVi) at 5.5 years
Description
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
Time Frame
5.5 years
Title
Death from any cause at 5.5 years
Description
Secondary endpoint measured from all cause death
Time Frame
5.5 years
Title
Death from any cardiovascular cause at 5.5 years
Description
Secondary endpoint measured from death due to cardiovascular causes
Time Frame
5.5 years
Title
Hospitalization for heart failure at 5.5 years
Description
Secondary endpoint measured from first hospitalization for heart failure
Time Frame
5.5 years
Title
Cardiovascular hospitalization at 5.5 years
Description
Secondary endpoint measured from first hospitalization for cardiovascular disease
Time Frame
5.5 years
Title
Change in NYHA Classification at 12 months
Description
Secondary endpoint measured from New York Heart Association class
Time Frame
12 months
Title
Change in Six Minute Walk Test performance at 12 months
Description
Secondary endpoint measured from Six Minute Walk Test
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Appropriate ICD therapy for ventricular arrhythmias
Description
Antitachycardia pacing or ICD shocks
Time Frame
5.5 years
Title
Change in NT-proBNP at 12 months
Description
Measurement of heart failure serum biomarker NT-proBNP
Time Frame
12 months
Title
Change in Left Ventricular Ejection Fraction (LVEF) at 12 months
Description
Measurement of LVEF before and at 12 months after implant using echocardiography
Time Frame
12 months
Title
Incidence of atrial tachyarrhythmia events
Description
Atrial arrhythmia event measured through cIED
Time Frame
5.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
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 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 return for follow-up visits due to the distance from the clinic.
Participants who do not anticipate being a resident of the area for the scheduled duration of the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mihail G Chelu, MD, PhD
Phone
7137987291
Email
leftvsleft@bcm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Merin Thomas
Phone
7137987291
Email
merin.thomas@bcm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mihail G Chelu, MD, PhD
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kenneth A Ellenbogen, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Left vs Left Randomized Clinical Trial
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