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LEft Bundle branchArea Pacing to Avoid Pacing-induced CARdiomyopathy (LEAP-CAR)

Primary Purpose

Bradycardia, Heart Failure, Pacemaker-Induced Cardiomyopathy

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Left bundle branch area pacing (LBBAP)
Right ventricular pacing (RVP)
Sponsored by
Azienda Ospedaliero Universitaria Maggiore della Carita
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Bradycardia focused on measuring left bundle branch area pacing, conduction system pacing, physiologic pacing, pacing-induced cardiomyopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: advanced AVB (frequent 2° degree or 3° degree AVB, atrial fibrillation - AF - with advanced AV block) and preserved or slightly reduced LVEF (>45%) Exclusion Criteria: LVEF ≤45% signs or symptoms of heart failure at enrollment unstable angina or acute coronary syndrome <3 months percutaneous coronary intervention or coronary-artery bypass surgery <3 months life expectancy <6 months previous hospitalization for heart failure evidence of pulmonary artery hypertension of any origin valvular disease greater than moderate previous heart transplant pregnancy

Sites / Locations

  • Hospital "Maggiore della Carità", Division of CardiologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Left bundle branch area pacing (LBBAP)

Right ventricular pacing (RVP)

Arm Description

Implant of the ventricular lead of the pacemaker in the left bundle branch area

Implant of the ventricular lead of the pacemaker in a conventional site for pacing (apex/paraapical interventricular septum)

Outcomes

Primary Outcome Measures

Absolute and relative value of LVEF (left ventricular ejection fraction) difference between two arms at follow-up
comparison of LVEF by transthoracic echocardiography at 12 months between the two arms (LBBAP vs RV pacing).

Secondary Outcome Measures

success rate
Percentages of unsuccessful procedure in the two arms (LBBAP vs RV pacing)
Distance covered at 6'WT (meters)
Comparison of distance covered at 6'WT at 12 months between the two arms (LBBAP vs RV pacing)
Score of quality of life (n: Higher value = worst outcome)
Comparison of MLHFQ score at 12 months between the two arms (LBBAP vs RV pacing)
Intra-patient evolution of LVEF
Comparison of variation in LVEF (absolute and %) from baseline to 12 months in the two arms (LBBAP and RV pacing, baseline vs 12 months follow up)
Intra-patient evolution of 6'WT (meters difference)
Comparison of variation in distance covered at 6'WT from baseline to 12 months between the two arms (LBBAP vs RV pacing)
Intra-patient evolution of quality of life
Comparison of variation in MLHFQ score from baseline to 12 months between the two arms (LBBAP vs RV pacing).
evolution of atrioventricular valves regurgitation
Percentages of patients with mitral/tricuspid regurgitation at least moderate at 12 months by echocardiography in the two arms (LBBAP vs RV pacing)

Full Information

First Posted
June 9, 2023
Last Updated
June 16, 2023
Sponsor
Azienda Ospedaliero Universitaria Maggiore della Carita
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1. Study Identification

Unique Protocol Identification Number
NCT05910866
Brief Title
LEft Bundle branchArea Pacing to Avoid Pacing-induced CARdiomyopathy
Acronym
LEAP-CAR
Official Title
LEft Bundle branchArea Pacing to Avoid Pacing-induced CARdiomyopathy: the LEAP-CAR Prospective, Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 10, 2023 (Anticipated)
Primary Completion Date
June 10, 2025 (Anticipated)
Study Completion Date
June 10, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliero Universitaria Maggiore della Carita

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
LEAP-CAR will evaluate the benefit of left bundle branch area pacing (LBBAP), comparing to conventional right ventricular pacing (RVP), in preventing pacing-induced cardiomyopathy (PICM) in patients undergoing pacemaker implant for advanced (2° or 3° degree) atrioventricular block, with baseline left ventricular ejection fraction (LVEF) >45%. LEAP-CAR is a randomized, prospective, double blind clinical trial.
Detailed Description
Pacing induced cardiomyopathy (PICM) is the deleterious effect of right ventricular (RV) pacing in patients receiving a permanent cardiac pacemaker (PM) for bradycardia. It is usually defined as a decrease in left ventricular (LV) function, generally expressed as ejection fraction (EF) decline, and it is mostly explained by the abnormal electrical and mechanical biventricular activation sequence induced by RV pacing. Several studies reported an incidence of PICM ranging from 10-20% of patients after 2-4 years of at least 20% RV pacing burden and reported an increase in heart failure (HF) and hospitalization in such patients. Permanent His Bundle Pacing (HBP) maintains normal electromechanical biventricular activation by means of the intrinsic conduction system and is therefore considered in patients with EF >40% and anticipated >20% of ventricular pacing, and may be used as an alternative to CRT in case of "ablate and pace" therapy for uncontrolled supraventricular arrhythmias. Left bundle branch area pacing (LBBAP) is a novel way to pace the conduction system of the heart, overcoming the drawbacks of HBP (suboptimal electrical measures, increased procedural and fluoroscopy time, loss of conduction system capture at follow-up). Evidence is building in adopting LBBAP instead of conventional CRT; LBBAP may have the potential to avoid PICM in patients needing permanent pacing for bradycardia. Aim of our study is to assess if LBBAP prevents PICM in patients with preserved EF needing RV pacing for advanced atrioventricular block (AVB). STUDY DESIGN Single-blind, 1:1 randomized, multicenter, prospective study. All consecutive patients with advanced AVB (frequent 2° degree or 3° degree AVB, atrial fibrillation - AF - with advanced AV block) and preserved or slightly reduced LVEF (>45%) receiving permanent PM will be randomized to LBBAP or RV (myocardial/parapical) pacing, according to a prespecified, automatically generated randomization list. The device will be implanted according to current optimal clinical practice, using clinically available stylet-driven or delivery-driven pacing leads. Choice of leads and device (single chamber in AF patients, dual chamber in sinus rhythm - SR) will be made according to operator preference and current clinical indications. Exclusion criteria will be: LVEF ≤45%; signs or symptoms of heart failure at enrollment; unstable angina or acute coronary syndrome <3 months; percutaneous coronary intervention or coronary-artery bypass surgery <3 months; life expectancy <6 months; previous hospitalization for heart failure; evidence of pulmonary artery hypertension of any origin; valvular disease greater than moderate; previous heart transplant; pregnancy. Baseline assessment will include: baseline ECG; echocardiography; measurement of the distance covered on a 6-minute walk (6'WT); quality-of-life assessment by Minnesota LIVING WITH HEART FAILURE® Questionnaire (MLHFQ). All patients will receive a follow-up visit at 3 and 12 months, when ECG, electrical follow-up of the PM and assessment of adverse events will be performed; echocardiography, MLHFQ and 6'WT will be performed at 12 months. Echocardiography and 6'WT will be done by a Cardiologist unaware of the randomization assignment. Echocardiographic images will be stored and evaluated by a specialist who will be unaware of the assigned treatment. Echocardiography will assess left ventricular function (LVEF) and volumes, preferably by automated 3D analysis. Strain analysis will be performed as adjunctive evaluation as per Center standard clinical practice; data on LV diastolic function and concomitant valve diseases will be also collected. PMs will be programmed in both arms in DDD or DDDR mode, with fixed or rate-adaptive AV delays no longer than 180 ms and de-activating algorithms promoting spontaneous AV conduction (i.e. reverse mode change, or AV hysteresis..), in case of SR; in VVI or VVIR in case of AF. Maintenance of unmodified pharmacological therapy will be encouraged until follow-up completion to avoid confounders. Primary endpoint will be the comparison of LVEF by transthoracic echocardiography at 12 months between the two arms (LBBAP vs RV pacing). Secondary endpoints will be: Percentages of unsuccessful procedure in the two arms (LBBAP vs RV pacing) Comparison of distance covered at 6'WT at 12 months between the two arms (LBBAP vs RV pacing) Comparison of MLHFQ score at 12 months between the two arms (LBBAP vs RV pacing) Comparison of variation in LVEF from baseline to 12 months in the two arms (LBBAP and RV pacing, baseline vs 12 months follow up) Comparison of variation in distance covered at 6'WT from baseline to 12 months between the two arms (LBBAP vs RV pacing) Comparison of variation in MLHFQ score from baseline to 12 months between the two arms (LBBAP vs RV pacing). Percentages of patients with mitral/tricuspid regurgitation at least moderate at 12 months by echocardiography in the two arms (LBBAP vs RV pacing) Extended follow-up of 2 years will be promoted to assess development of symptomatic heart failure (i.e. any hospitalization for heart failure or starting of medications for heart failure) or mortality. This extended follow-up will not be mandatory as per protocol. STATISTICAL ANALYSIS Data will be evaluated according to an intention to treat analysis, keeping track of treatment crossover for "per protocol" analyses, anticipating a potential failure in 3% of LBBAP group, leading to RV pacing in those patients. Continuous variables with normal distribution will be expressed as mean +/- standard deviation (SD) and compared by two-tailed t-test; non-normally distributed variables will be expressed as median (25-75% interquartile range) and compared by Wilcoxon-Mann-Whitney test. Normality will be assessed by Kolomorgov-Smirnov test. Categorical data will be expressed as percentage and compared by chi-square test. P values <0.05 will be considered statistically significant. SAMPLE SIZE CALCULATION Estimating a normal mean baseline LVEF of 55% and a predicted reduction of 5% (11,1) in RV apical pacing patients comparing to LBBAP, the following calculations were made: Continuous Endpoint, Two Independent Sample Study Sample Size Group 1 63 Group 2 63 Total 126 Study Parameters Mean, group 1 55 Mean, group 2 5010% dec Alpha 0.05 Beta 0.2 Power 0.8 Anticipating potential dropout, sample size will be rounded to 130 patients. Interim analysis will be carried out when half the sample size will complete 1-year follow-up to confirm adequacy of enrollment and to analyze the trend of the primary endpoint. Our calculations were modeled after the PACE trial design, that assessed similar endpoints comparing CRT and RV pacing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bradycardia, Heart Failure, Pacemaker-Induced Cardiomyopathy, Conduction Block, Atrioventricular, Cardiac Remodeling, Ventricular
Keywords
left bundle branch area pacing, conduction system pacing, physiologic pacing, pacing-induced cardiomyopathy

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Left bundle branch area pacing (LBBAP)
Arm Type
Experimental
Arm Description
Implant of the ventricular lead of the pacemaker in the left bundle branch area
Arm Title
Right ventricular pacing (RVP)
Arm Type
Active Comparator
Arm Description
Implant of the ventricular lead of the pacemaker in a conventional site for pacing (apex/paraapical interventricular septum)
Intervention Type
Device
Intervention Name(s)
Left bundle branch area pacing (LBBAP)
Intervention Description
Pacing of the conduction system of the heart to obtain physiological activation
Intervention Type
Device
Intervention Name(s)
Right ventricular pacing (RVP)
Intervention Description
Conventional ventricular pacing
Primary Outcome Measure Information:
Title
Absolute and relative value of LVEF (left ventricular ejection fraction) difference between two arms at follow-up
Description
comparison of LVEF by transthoracic echocardiography at 12 months between the two arms (LBBAP vs RV pacing).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
success rate
Description
Percentages of unsuccessful procedure in the two arms (LBBAP vs RV pacing)
Time Frame
1 year
Title
Distance covered at 6'WT (meters)
Description
Comparison of distance covered at 6'WT at 12 months between the two arms (LBBAP vs RV pacing)
Time Frame
1 year
Title
Score of quality of life (n: Higher value = worst outcome)
Description
Comparison of MLHFQ score at 12 months between the two arms (LBBAP vs RV pacing)
Time Frame
1 year
Title
Intra-patient evolution of LVEF
Description
Comparison of variation in LVEF (absolute and %) from baseline to 12 months in the two arms (LBBAP and RV pacing, baseline vs 12 months follow up)
Time Frame
1 year
Title
Intra-patient evolution of 6'WT (meters difference)
Description
Comparison of variation in distance covered at 6'WT from baseline to 12 months between the two arms (LBBAP vs RV pacing)
Time Frame
1 year
Title
Intra-patient evolution of quality of life
Description
Comparison of variation in MLHFQ score from baseline to 12 months between the two arms (LBBAP vs RV pacing).
Time Frame
1 year
Title
evolution of atrioventricular valves regurgitation
Description
Percentages of patients with mitral/tricuspid regurgitation at least moderate at 12 months by echocardiography in the two arms (LBBAP vs RV pacing)
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Heart failure hospitalization and mortality
Description
any hospitalization for heart failure or starting of medications for heart failure or mortality
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: advanced AVB (frequent 2° degree or 3° degree AVB, atrial fibrillation - AF - with advanced AV block) and preserved or slightly reduced LVEF (>45%) Exclusion Criteria: LVEF ≤45% signs or symptoms of heart failure at enrollment unstable angina or acute coronary syndrome <3 months percutaneous coronary intervention or coronary-artery bypass surgery <3 months life expectancy <6 months previous hospitalization for heart failure evidence of pulmonary artery hypertension of any origin valvular disease greater than moderate previous heart transplant pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriele Dell'Era, MD
Phone
03213733294
Ext
+39
Email
gabriele.dellera@maggioreosp.novara.it
First Name & Middle Initial & Last Name or Official Title & Degree
Chiara Ghiglieno, MD
Phone
03213733294
Ext
+39
Email
chiara.ghiglieno@maggioreosp.novara.it
Facility Information:
Facility Name
Hospital "Maggiore della Carità", Division of Cardiology
City
Novara
ZIP/Postal Code
28100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriele Dell'Era, MD
Phone
03213733590
Email
gabriele.dellera@maggioreosp.novara.it
First Name & Middle Initial & Last Name & Degree
Chiara Ghiglieno, MD
Phone
03213733590
Email
chiara.ghiglieno@maggioreosp.novara.it
First Name & Middle Initial & Last Name & Degree
Chiara Ghiglieno, MD
First Name & Middle Initial & Last Name & Degree
Federica De Vecchi, MD
First Name & Middle Initial & Last Name & Degree
Matteo Santagostino, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Data will be shared according to motivated request, after publication of results of the study

Learn more about this trial

LEft Bundle branchArea Pacing to Avoid Pacing-induced CARdiomyopathy

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