Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05910866 |
| Other study ID # |
CE084/2023 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 10, 2023 |
| Est. completion date |
June 10, 2026 |
Study information
| Verified date |
January 2024 |
| Source |
Azienda Ospedaliero Universitaria Maggiore della Carita |
| Contact |
Gabriele Dell'Era, MD |
| Phone |
03213733294 |
| Email |
gabriele.dellera[@]maggioreosp.novara.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
