Left vs Left Randomized Clinical Trial

NCT05650658 | Recruiting DMC FDA Device

• 1 other identifier: PLACER 2021C3- 24160
• Study Type: interventional
• Target: 2,136
• Locations: 2 countries
• Sites: 71

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.

Conditions

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

Outcome Measures

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.

  5.5 years

Secondary Outcomes (14)

• Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months

  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

  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

  5.5 years

• Death from any cause at 5.5 years

  5.5 years

• Death from any cardiovascular cause at 5.5 years

  5.5 years

Other Outcomes (3)

• Appropriate ICD therapy for ventricular arrhythmias

  5.5 years

• Incidence of atrial tachyarrhythmia events

  5.5 years

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

  12 months

Study Arms (2)

His/Left Bundle Branch Pacing (His/LBBP)

ACTIVE COMPARATOR

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

Biventricular Pacing (BiVP)

ACTIVE COMPARATOR

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

His/LBBP DEVICE

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%.

His/Left Bundle Branch Pacing (His/LBBP)

BiVP DEVICE

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.

Biventricular Pacing (BiVP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Patient-Centered Outcomes Research Institute: collaborator
• University of Utah: collaborator
• Virginia Commonwealth University: collaborator
• Cleveland Clinic Florida: collaborator
• East Carolina University: collaborator

Study Sites (71)

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

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

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

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

RECRUITING

Rush University

Chicago, Illinois, 60612, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Northwestern University

Evanston, Illinois, 60208, United States

RECRUITING

CIS Clinical Research Corporation

Naperville, Illinois, 60540, United States

ENROLLING BY INVITATION

Trustees of Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Baptist Health Louisville

Louisville, Kentucky, 40207, United States

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

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

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

RECRUITING

Novant Health

Charlotte, North Carolina, 28204, United States

RECRUITING

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

The MetroHealth System

Cleveland, Ohio, 44109, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

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

RECRUITING

Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

University of Pittsburg

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Geisinger Commonwealth School of Medicine

Scranton, Pennsylvania, 18510, United States

RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

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

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

RECRUITING

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

RECRUITING

Sentara Healthcare

Newport News, Virginia, 23606, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

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

RECRUITING

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

RECRUITING

Hamilton Health Sciences (HHS)

Hamilton, Ontario, Canada

RECRUITING

Newmarket Electrophysiology Research Group Inc. (NERG)

Newmarket, Ontario, Canada

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

RECRUITING

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

Kitchener, Canada

RECRUITING

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

Montreal, Canada

RECRUITING

Université Laval

Québec, Canada

RECRUITING

MeSH Terms

Conditions

Heart Failure; Atrioventricular Block

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Heart Block; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mihail G Chelu, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Kenneth A Ellenbogen, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mihail G Chelu, MD, PhD

CONTACT

7137987291; leftvsleft@bcm.edu

Merin Thomas

CONTACT

7137987291; merin.thomas@bcm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 14, 2022
• Study Start: September 13, 2023
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (14); US (57)