CClinicalTrials.gg
RecruitingNCT05650658Updated Oct 2, 2025

Left vs Left Randomized Clinical Trial

An interventional study of His/LBBP and BiVP in Heart Failure, Heart Failure With Reduced Ejection Fraction and AV Block, sponsored by Baylor College of Medicine. Recruiting at 71 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-02.

Sponsored by Baylor College of Medicine · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
2,136
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Heart Failure
  • Heart Failure With Reduced Ejection Fraction
  • AV Block
  • LBBB
  • RBBB
  • Intraventricular Conduction Delay
  • Pacing-Induced Cardiomyopathy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
2,136 participants (estimated)

Study arms

  • Active comparator
    His/Left Bundle Branch Pacing (His/LBBP)

    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.

    Device: His/LBBP

  • Active comparator
    Biventricular Pacing (BiVP)

    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.

    Device: BiVP

Interventions

  • DeviceHis/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%.

  • DeviceBiVP

    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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 5.5 years

Secondary outcomes

  1. 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.

    Time frame: 12 months

  2. 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

    Time frame: 5.5 years

  3. 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

    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

    Time frame: 5.5 years

  4. Death from any cause at 5.5 years

    Secondary endpoint measured from all cause death

    Time frame: 5.5 years

  5. Death from any cardiovascular cause at 5.5 years

    Secondary endpoint measured from death due to cardiovascular causes

    Time frame: 5.5 years

  6. Hospitalization for heart failure at 5.5 years

    Secondary endpoint measured from first hospitalization for heart failure

    Time frame: 5.5 years

  7. Cardiovascular hospitalization at 5.5 years

    Secondary endpoint measured from first hospitalization for cardiovascular disease

    Time frame: 5.5 years

  8. Total HF hospitalizations

    Total number of HF hospitalizations

    Time frame: 5.5 years

  9. Composite of cardiovascular death or first HF hospitalization

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

    Time frame: 5.5 years

  10. Composite cardiovascular death or HF hospitalization or heart transplant or durable left ventricular assist device

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

    Time frame: 5.5 years

  11. Change in NYHA Classification at 12 months

    Secondary endpoint measured from New York Heart Association class

    Time frame: 12 months

  12. Change in Six Minute Walk Test performance at 12 months

    Secondary endpoint measured from Six Minute Walk Test

    Time frame: 12 months

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

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

    Time frame: 12 months

  14. Change in NT-proBNP at 12 months

    Measurement of heart failure serum biomarker NT-proBNP

    Time frame: 12 months

Other outcomes

  1. Appropriate ICD therapy for ventricular arrhythmias

    Antitachycardia pacing or ICD shocks

    Time frame: 5.5 years

  2. Incidence of atrial tachyarrhythmia events

    Atrial arrhythmia event measured through cIED

    Time frame: 5.5 years

  3. Change in Left Ventricular Ejection Fraction (LVEF) at 12 months

    Measurement of LVEF before and at 12 months after implant using echocardiography

    Time frame: 12 months

06

Study locations

63 of 71 sites recruiting
  • Mercy Gilbert & Chandler Regional Medical Centers, Gilbert AZ
    Gilbert, Arizona 85297, United States
    Recruiting
  • University of Arizona College of Medicine- Phoenix
    Tucson, Arizona 85719, United States
    Recruiting
  • University of Arkansas for Medical Sciences (UAMS)
    Little Rock, Arkansas 72205, United States
    • Urvashi Kalola · Contact · ukalola@uams.edu · 0000000000
    • Subodh Devabhaktuni, MD · Principal investigator
    Recruiting
  • University of California San Diego
    La Jolla, California 92093, United States
    Recruiting
  • University of Colorado (Anschutz Medical Campus)
    Denver, Colorado 80217, United States
    Recruiting
  • South Denver Cardiology Associates
    Littleton, Colorado 80124, United States
    • Kathrin Siegel · Contact · ksiegel@southdenver.com · (303) 703-2162
    • Srikanth Sundaram, MD · Principal investigator
    Recruiting
  • Hartford Hospital
    Hartford, Connecticut 06102, United States
    Recruiting
  • Yale University
    New Haven, Connecticut 06511, United States
    Recruiting
  • Heart Rhythm Solutions
    Davie, Florida 33328, United States
    Recruiting
  • University of Florida Jacksonville
    Jacksonville, Florida 32211, United States
    Not yet recruiting
  • Mount Sinai Medical Center of Florida, Inc.
    Miami Beach, Florida 33140, United States
    Not yet recruiting
  • Cleveland Clinic Florida
    Palm Beach Gardens, Florida 33418, United States
    • Maria Gomez Mejia · Contact · MEJIAGM@ccf.org · (954) 659-6204
    • Ricardo Hernandez, MD · Principal investigator
    Recruiting
  • Florida Heart and Vascular, LLC dba Florida Heart Rhythm Specialist, PLLC
    South Pasadena, Florida 33707, United States
    Not yet recruiting
  • University of South Florida
    Tampa, Florida 33613, United States
    • Jacky He · Contact · jackyhe@usf.edu · (813) 250-2462
    • Bengt Herweg, MD · Principal investigator
    Recruiting
  • Rush University
    Chicago, Illinois 60612, United States
    • Nusrat Jahan · Contact
    • Timothy Larsen, DO · Principal investigator
    Recruiting
  • University of Chicago
    Chicago, Illinois 60637, United States
    • Shahram Sarrafi · Contact
    • Gaurav Upadhyay, MD · Principal investigator
    Recruiting
  • Northwestern University
    Evanston, Illinois 60208, United States
    • Katrina Martin · Contact · katrina.martin@nm.org · (312) 695-4067
    • Nishant Verma, MD · Principal investigator
    Recruiting
  • CIS Clinical Research Corporation
    Naperville, Illinois 60540, United States
    Enrolling by invitation
  • Trustees of Indiana University
    Indianapolis, Indiana 46202, United States
    • Molly Stearns · Contact · mstearns2@IUHEALTH.ORG · (317) 962-1130
    • Antonio Navarrete, MD · Principal investigator
    Recruiting
  • Baptist Health Louisville
    Louisville, Kentucky 40207, United States
    • Karin Cryan · Contact · karin.cryan@BHSI.COM · 0000000000
    • John Mandrola, MD · Principal investigator
    Recruiting
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
    Recruiting
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
    Recruiting
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
    Recruiting
  • HMH Hospitals Corporation
    Hackensack, New Jersey 07601, United States
    Recruiting
  • Virtua Health
    Marlton, New Jersey 08053, United States
    • Marisa Brown · Contact · Mbrown3@virtua.org · (856) 355-1226
    • Aatish Garg, MD · Principal investigator
    Recruiting
  • Newark Beth Israel Medical Center
    Newark, New Jersey 07112, United States
    Recruiting
  • The Valley Hospital, Inc.
    Ridgewood, New Jersey 07450, United States
    Recruiting
  • Lovelace Medical Center
    Albuquerque, New Mexico 87102, United States
    • Zinai Tellez · Contact
    • Sean Mazer · Principal investigator
    Recruiting
  • Weill Cornell Medicine
    New York, New York 10021, United States
    Recruiting
  • Icahn School of Medicine at Mount Sinai
    New York, New York 10029, United States
    Recruiting
  • Columbia University Medical Center/New York-Presbyterian Hospital (CUMC/NYPH)
    New York, New York 10032, United States
    Not yet recruiting
  • MH Mission Hospital LLLP- Asheville Cardiology Associates
    Asheville, North Carolina 28803, United States
    Recruiting
  • University of North Carolina
    Chapel Hill, North Carolina 27599, United States
    • Elias Wen · Contact · emwen@email.unc.edu · 0000000000
    • Anil Gehi, MD · Principal investigator
    Recruiting
  • Novant Health
    Charlotte, North Carolina 28204, United States
    • Darren N Crawford · Contact
    • Thomas Kambur · Principal investigator
    Recruiting
  • The Christ Hospital
    Cincinnati, Ohio 45219, United States
    Recruiting
  • The MetroHealth System
    Cleveland, Ohio 44109, United States
    • Pete Leo · Contact · pleo@metrohealth.org · (216) 778-2714
    • Soufian Almahameed, MD · Principal investigator
    Recruiting
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
    • Raquel Rozich · Contact · Rozichr@ccf.org · 0000000000
    • Roy Chung, MD · Principal investigator
    Recruiting
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
    • Liz Cannard · Contact · cannarde@ohsu.edu · 0000000000
    • Eric Stecker, MD · Principal investigator
    Recruiting
  • St. Luke's University Health Network
    Allentown, Pennsylvania 18015, United States
    Recruiting
  • Lehigh Valley Hospital Inc.
    Allentown, Pennsylvania 18103, United States
    Recruiting
  • Penn Medicine Lancaster General
    Lancaster, Pennsylvania 17603, United States
    Recruiting
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
    Recruiting
  • Thomas Jefferson University Hospital
    Philadelphia, Pennsylvania 19107, United States
    • Mckenna Krall · Contact
    • Behzad Pavri · Principal investigator
    Recruiting
  • Allegheny-Singer Research Institute
    Pittsburgh, Pennsylvania 15212, United States
    • Minesh Lathia · Contact · minesh.lathia@ahn.org · (412) 359-8468
    • Joshua Silverstein, MD · Principal investigator
    Recruiting
  • University of Pittsburg
    Pittsburgh, Pennsylvania 15213, United States
    • Sherry Pellegrino · Contact · pellegrinosl@upmc.edu · (412) 647-8210
    • Krishna Kancharla, MD · Principal investigator
    Recruiting
  • Geisinger Commonwealth School of Medicine
    Scranton, Pennsylvania 18510, United States
    • Grace E Hughes · Contact
    • Jess Oren, MD · Principal investigator
    Recruiting
  • Medical University of South Carolina (MUSC)
    Charleston, South Carolina 29425, United States
    • Olivia Washington · Contact · washoliv@musc.edu · (843) 792-0464
    • Anne Kroman, MD · Principal investigator
    Recruiting
  • Prisma Health-Upstate
    Greenville, South Carolina 29605, United States
    Not yet recruiting
  • Texas Health Research & Education Institute
    Arlington, Texas 76011, United States
    Not yet recruiting
  • Baylor College of Medicine
    Houston, Texas 77030, United States
    • Stephen Harold · Contact · harold@bcm.edu · (713) 798-7227
    • Mihail Chelu, MD · Principal investigator
    Recruiting
  • St. Mark's Hospital
    Salt Lake City, Utah 84124, United States
    Recruiting
  • University of Vermont
    Burlington, Vermont 05402, United States
    Recruiting
  • University of Virginia Health System
    Charlottesville, Virginia 22908, United States
    • Katie L Sullivan · Contact
    • Rohit Malhotra · Principal investigator
    Recruiting
  • Inova Heart and Vascular Institute
    Falls Church, Virginia 22042, United States
    Recruiting
  • Sentara Healthcare
    Newport News, Virginia 23606, United States
    • Linette Klevan · Contact
    • Erich Kiehl · Principal investigator
    Recruiting
  • Virginia Commonwealth University
    Richmond, Virginia 23284, United States
    • Melissa Sears · Contact
    • Jordana Kron, MD · Principal investigator
    Recruiting
  • University of Washington
    Seattle, Washington 98195, United States
    • Adele Stefanowicz · Contact · amstef99@uw.edu · 0000000000
    • Kristen Patton, MD · Principal investigator
    Recruiting
  • Mazankowski Alberta Heart Institute/University of Alberta
    Edmonton, Alberta, Canada
    Not yet recruiting
  • University of British Columbia
    Vancouver, British Columbia, Canada
    Recruiting
  • Victoria Cardiac Arrhythmia Trials (VCAT) Inc.
    Victoria, British Columbia, Canada
    • Matthew Coxon · Contact · mcoxon@catrials.org · (250) 595-0400
    • Laurence Sterns, MD · Principal investigator
    Recruiting
  • Nova Scotia Health Authority
    Halifax, Nova Scotia, Canada
    Recruiting
  • Hamilton Health Sciences (HHS)
    Hamilton, Ontario, Canada
    • Kiran Qamar · Contact · qamarulisl@HHSC.CA · (905) 521-2100
    • Jorge Wong, MD · Principal investigator
    Recruiting
  • Newmarket Electrophysiology Research Group Inc. (NERG)
    Newmarket, Ontario, Canada
    • Lynn Nyman · Contact · lnyman@southlake.ca · (905) 895-4521
    • Mouhannad Sadek, MD · Principal investigator
    Recruiting
  • University of Ottawa Heart Institute
    Ottawa, Ontario, Canada
    Recruiting
  • Sunnybrook Research Institute
    Toronto, Ontario, Canada
    Recruiting
  • Montreal Heart Institute
    Montreal, Quebec, Canada
    Recruiting
  • CIUSSS de l'Estrie - CHUS
    Saint-Jean-sur-Richelieu, Quebec, Canada
    Not yet recruiting
  • University of Calgary
    Calgary, Canada
    • Nirav Bhagat · Contact
    • Derek Exner · Principal investigator
    Recruiting
  • Waterloo Wellington Cardiovascular Research Institute (WWCRI) - St. Mary's General Hospital
    Kitchener, Canada
    • Mary Radyk · Contact
    • Claus Rinne · Principal investigator
    Recruiting
  • Research Institute of the McGill University Health Centre (RI-MUHC) - MUHC, Montreal General Hospital
    Montreal, Canada
    • Fiorella Rafti · Contact
    • Jacqueline Joza · Principal investigator
    Recruiting
  • Université Laval
    Québec, Canada
    Recruiting
07

References and documents

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. PubMed 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. PubMed 39481799 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT05650658
Lead sponsor
Baylor College of Medicine
Collaborators
Patient-Centered Outcomes Research Institute, University of Utah, Virginia Commonwealth University, Cleveland Clinic Florida, East Carolina University
Responsible party
Mihail Gabriel Chelu (Associate Professor, Baylor College of Medicine) — Principal investigator
First posted
Dec 14, 2022
Start date
Sep 13, 2023
Primary completion
Jun 30, 2029 (estimated)
Completion
Jun 30, 2029 (estimated)
Last update
Oct 2, 2025

Study contacts

Mihail G Chelu, MD, PhD
Contact
leftvsleft@bcm.edu
7137987291
Merin Thomas
Contact
merin.thomas@bcm.edu
7137987291
Mihail G Chelu, MD, PhD
principal investigator · Baylor College of Medicine
Kenneth A Ellenbogen, MD
principal investigator · Virginia Commonwealth University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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