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| Name | Class |
|---|---|
| Patient-Centered Outcomes Research Institute | OTHER |
| University of Utah | OTHER |
| Virginia Commonwealth University | OTHER |
| Cleveland Clinic Florida |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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%. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Appropriate ICD therapy for ventricular arrhythmias | Antitachycardia pacing or ICD shocks | 5.5 years |
| Incidence of atrial tachyarrhythmia events | Atrial arrhythmia event measured through cIED |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mihail G Chelu, MD, PhD | Contact | 7137987291 | leftvsleft@bcm.edu | |
| Merin Thomas | Contact | 7137987291 | merin.thomas@bcm.edu |
| Name | Affiliation | Role |
|---|---|---|
| Mihail G Chelu, MD, PhD | Baylor College of Medicine | Principal Investigator |
| Kenneth A Ellenbogen, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mercy Gilbert & Chandler Regional Medical Centers, Gilbert AZ | Recruiting | Gilbert | Arizona | 85297 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40250827 | Derived | 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. | |
| 39481799 | Derived | 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. |
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| OTHER |
| East Carolina University | OTHER |
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| 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. |
|
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 |
| 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 | 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 | 5.5 years |
| Death from any cause at 5.5 years | Secondary endpoint measured from all cause death | 5.5 years |
| Death from any cardiovascular cause at 5.5 years | Secondary endpoint measured from death due to cardiovascular causes | 5.5 years |
| Hospitalization for heart failure at 5.5 years | Secondary endpoint measured from first hospitalization for heart failure | 5.5 years |
| Cardiovascular hospitalization at 5.5 years | Secondary endpoint measured from first hospitalization for cardiovascular disease | 5.5 years |
| Total HF hospitalizations | Total number of HF hospitalizations | 5.5 years |
| Composite of cardiovascular death or first HF hospitalization | Secondary endpoint measured from cardiovascular death, first hospitalization for heart failure | 5.5 years |
| 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 | 5.5 years |
| Change in NYHA Classification at 12 months | Secondary endpoint measured from New York Heart Association class | 12 months |
| Change in Six Minute Walk Test performance at 12 months | Secondary endpoint measured from Six Minute Walk Test | 12 months |
| Patient activity measured through cardiovascular implantable electronic devices (CIED) at 12 months | Measurement Patient activity measured through cardiovascular implantable electronic devices (CIED) | 12 months |
| Change in NT-proBNP at 12 months | Measurement of heart failure serum biomarker NT-proBNP | 12 months |
| 5.5 years |
| Change in Left Ventricular Ejection Fraction (LVEF) at 12 months | Measurement of LVEF before and at 12 months after implant using echocardiography | 12 months |
| University of Arizona College of Medicine- Phoenix | Recruiting | Tucson | Arizona | 85719 | United States |
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| University of Arkansas for Medical Sciences (UAMS) | Recruiting | Little Rock | Arkansas | 72205 | United States |
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| University of California San Diego | Recruiting | La Jolla | California | 92093 | United States |
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| University of Colorado (Anschutz Medical Campus) | Recruiting | Denver | Colorado | 80217 | United States |
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| South Denver Cardiology Associates | Recruiting | Littleton | Colorado | 80124 | United States |
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| Hartford Hospital | Recruiting | Hartford | Connecticut | 06102 | United States |
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| Yale University | Recruiting | New Haven | Connecticut | 06511 | United States |
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| Heart Rhythm Solutions | Recruiting | Davie | Florida | 33328 | United States |
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| University of Florida Jacksonville | Not yet recruiting | Jacksonville | Florida | 32211 | United States |
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| Mount Sinai Medical Center of Florida, Inc. | Not yet recruiting | Miami Beach | Florida | 33140 | United States |
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| Cleveland Clinic Florida | Recruiting | Palm Beach Gardens | Florida | 33418 | United States |
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| Florida Heart and Vascular, LLC dba Florida Heart Rhythm Specialist, PLLC | Not yet recruiting | South Pasadena | Florida | 33707 | United States |
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| University of South Florida | Recruiting | Tampa | Florida | 33613 | United States |
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| Rush University | Recruiting | Chicago | Illinois | 60612 | United States |
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| University of Chicago | Recruiting | Chicago | Illinois | 60637 | United States |
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| Northwestern University | Recruiting | Evanston | Illinois | 60208 | United States |
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| CIS Clinical Research Corporation | Enrolling by invitation | Naperville | Illinois | 60540 | United States |
| Trustees of Indiana University | Recruiting | Indianapolis | Indiana | 46202 | United States |
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| Baptist Health Louisville | Recruiting | Louisville | Kentucky | 40207 | United States |
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| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
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| Beth Israel Deaconess Medical Center | Recruiting | Boston | Massachusetts | 02215 | United States |
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| Mayo Clinic | Recruiting | Rochester | Minnesota | 55905 | United States |
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| HMH Hospitals Corporation | Recruiting | Hackensack | New Jersey | 07601 | United States |
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| Virtua Health | Recruiting | Marlton | New Jersey | 08053 | United States |
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| Newark Beth Israel Medical Center | Recruiting | Newark | New Jersey | 07112 | United States |
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| The Valley Hospital, Inc. | Recruiting | Ridgewood | New Jersey | 07450 | United States |
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| Lovelace Medical Center | Recruiting | Albuquerque | New Mexico | 87102 | United States |
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| Weill Cornell Medicine | Recruiting | New York | New York | 10021 | United States |
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| Icahn School of Medicine at Mount Sinai | Recruiting | New York | New York | 10029 | United States |
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| Columbia University Medical Center/New York-Presbyterian Hospital (CUMC/NYPH) | Not yet recruiting | New York | New York | 10032 | United States |
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| MH Mission Hospital LLLP- Asheville Cardiology Associates | Recruiting | Asheville | North Carolina | 28803 | United States |
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| University of North Carolina | Recruiting | Chapel Hill | North Carolina | 27599 | United States |
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| Novant Health | Recruiting | Charlotte | North Carolina | 28204 | United States |
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| The Christ Hospital | Recruiting | Cincinnati | Ohio | 45219 | United States |
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| The MetroHealth System | Recruiting | Cleveland | Ohio | 44109 | United States |
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| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
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| Oregon Health & Science University | Recruiting | Portland | Oregon | 97239 | United States |
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| St. Luke's University Health Network | Recruiting | Allentown | Pennsylvania | 18015 | United States |
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| Lehigh Valley Hospital Inc. | Recruiting | Allentown | Pennsylvania | 18103 | United States |
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| Penn Medicine Lancaster General | Recruiting | Lancaster | Pennsylvania | 17603 | United States |
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| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| Thomas Jefferson University Hospital | Recruiting | Philadelphia | Pennsylvania | 19107 | United States |
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| Allegheny-Singer Research Institute | Recruiting | Pittsburgh | Pennsylvania | 15212 | United States |
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| University of Pittsburg | Recruiting | Pittsburgh | Pennsylvania | 15213 | United States |
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| Geisinger Commonwealth School of Medicine | Recruiting | Scranton | Pennsylvania | 18510 | United States |
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| Medical University of South Carolina (MUSC) | Recruiting | Charleston | South Carolina | 29425 | United States |
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| Prisma Health-Upstate | Not yet recruiting | Greenville | South Carolina | 29605 | United States |
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| Texas Health Research & Education Institute | Not yet recruiting | Arlington | Texas | 76011 | United States |
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| Baylor College of Medicine | Recruiting | Houston | Texas | 77030 | United States |
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| St. Mark's Hospital | Recruiting | Salt Lake City | Utah | 84124 | United States |
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| University of Vermont | Recruiting | Burlington | Vermont | 05402 | United States |
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| University of Virginia Health System | Recruiting | Charlottesville | Virginia | 22908 | United States |
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| Inova Heart and Vascular Institute | Recruiting | Falls Church | Virginia | 22042 | United States |
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| Sentara Healthcare | Recruiting | Newport News | Virginia | 23606 | United States |
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| Virginia Commonwealth University | Recruiting | Richmond | Virginia | 23284 | United States |
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| University of Washington | Recruiting | Seattle | Washington | 98195 | United States |
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| Mazankowski Alberta Heart Institute/University of Alberta | Not yet recruiting | Edmonton | Alberta | Canada |
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| University of British Columbia | Recruiting | Vancouver | British Columbia | Canada |
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| Victoria Cardiac Arrhythmia Trials (VCAT) Inc. | Recruiting | Victoria | British Columbia | Canada |
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| Nova Scotia Health Authority | Recruiting | Halifax | Nova Scotia | Canada |
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| Hamilton Health Sciences (HHS) | Recruiting | Hamilton | Ontario | Canada |
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| Newmarket Electrophysiology Research Group Inc. (NERG) | Recruiting | Newmarket | Ontario | Canada |
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| University of Ottawa Heart Institute | Recruiting | Ottawa | Ontario | Canada |
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| Sunnybrook Research Institute | Recruiting | Toronto | Ontario | Canada |
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| Montreal Heart Institute | Recruiting | Montreal | Quebec | Canada |
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| CIUSSS de l'Estrie - CHUS | Not yet recruiting | Saint-Jean-sur-Richelieu | Quebec | Canada |
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| University of Calgary | Recruiting | Calgary | Canada |
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| Waterloo Wellington Cardiovascular Research Institute (WWCRI) - St. Mary's General Hospital | Recruiting | Kitchener | Canada |
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| Research Institute of the McGill University Health Centre (RI-MUHC) - MUHC, Montreal General Hospital | Recruiting | Montreal | Canada |
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| Université Laval | Recruiting | Québec | Canada |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D054537 | Atrioventricular Block |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D006327 | Heart Block |
| D001145 | Arrhythmias, Cardiac |
| D000075224 | Cardiac Conduction System Disease |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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