Clinical trial NCT04595487: LVSP vs RVP in Patients With AV Conduction Disorders
Official title: Permanent Left Ventricular Septal Pacing Versus Right Ventricular Pacing in Patients With Atrioventricular Conduction Disorders: a Randomized Trial: LEAP Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Pacing
Pacing-Induced Cardiomyopathy
Conduction System Pacing
Left Ventricular Septal Pacing
Atrioventricular Block
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Medtronic
First posted: 2020-10-20
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale:

Permanent cardiac pacing is the only available therapy in patients with atrioventricular (AV) conduction disorders and can be life-saving. Right ventricular pacing (RVP), the routine clinical practice for decades in these patients, is non-physiologic, leads to dyssynchronous electrical and mechanical activation of the ventricles, and may cause pacing-induced cardiomyopathy and heart failure.

Left ventricular septal pacing (LVSP) is an emerging form of physiologic pacing that can possibly overcome the adverse effects of RVP.

Study design and hypotheses:

The LEAP trial is a multi-center investigator-initiated, prospective, randomized controlled, open label, blinded endpoint evaluation (PROBE) study that compares LVSP with conventional RVP. A total of four hundred seventy patients with a class I or IIa indication for pacemaker implantation due to AV conduction disorders and an expected ventricular pacing percentage \>20% will be randomized 1:1 to LVSP or RVP. The primary endpoint is a composite endpoint of all-cause mortality, hospitalization for heart failure and a more than 10% decrease in left ventricular ejection fraction (LVEF) in absolute terms leading to a LVEF below 50% at one year follow-up. LVSP is anticipated to result in improved outcomes.

Secondary objectives are to evaluate whether LVSP is cost-effective and associated with an improved quality of life (QOL) as compared to RVP. Quality of life is expected to improve with LVSP and reduced healthcare resource utilizations are expected to ensure lower costs in the LVSP group during follow-up, despite initial higher costs of the implantation.

Study design: Multi-center investigator-initiated, prospective, randomized controlled, open label, blinded endpoint evaluation (PROBE) study.

Study population: Adult patients with a bradycardia-pacing indication because of AV conduction disorders with an expected ventricular pacing percentage of ≥ 20% and a left ventricular ejection fraction (LVEF) \>/= 40%. Four hundred seventy patients will be randomized 1:1 to LVSP or RVP.

Intervention: LVSP vs RVP.

Main study parameters/endpoints:

The primary endpoint is a composite of all-cause mortality, hospitalization for heart failure, and a more than 10% point decrease in left ventricular ejection fraction (LVEF) leading to an LVEF below 50%, which as a binary combined endpoint will be determined at one year follow-up.

Secondary endpoints are:

* Time to first occurrence of all cause mortality or hospitalization for heart failure.
* Time to first occurrence of all cause mortality.
* Time to first occurrence of hospitalization for heart failure.
* Time to first occurrence of atrial fibrillation (AF) de novo.
* The echocardiographic changes in LVEF at one year.
* The echocardiographic changes in diastolic (dys-)function at one year.
* The occurrence of pacemaker related complications.
* Quality of life (QOL), cost-effectiveness analyses (CEA) and budget impact analysis (BIA).

The secondary endpoints (other than echocardiographic LVEF change) will be determined at the end of the follow-up period, when the last included patient has reached one year follow-up. The individual follow-up time for patients at this time point will vary with a minimum of one year.


Eligibility criteria: Inclusion Criteria:

* Age \> 18y
* Life expectancy with good functional status of \> 1y
* Class I or IIa pacemaker indication due to AV conduction disorder

  * Acquired 3rd or 2nd degree AVB
  * Atrial arrhythmia with slow ventricular conduction
* Expected ventricular pacing percentage \> 20%
* LVEF \>/= 40%
* Signed and dated informed consent form

Exclusion Criteria:

* HF NYHA class III-IV
* Class I indication for CRT
* Class I indication for ICD
* Previous implanted CIED (except for ILR)
* Atrial arrhythmia with planned AV junction ablation
* PCI or CABG \<30 days before enrollment
* Valvular heart disease with indication for valve repair or replacement
* Hypertrophic cardiomyopathy with interventricular septum thickness \> 2 cm
* Renal insufficiency requiring hemodialysis
* Active infectious disease or malignancy
* Pregnancy

Primary outcomes:
measure: Binary combined endpoint consisting of all-cause mortality, hospitalization for heart failure, and a more than 10% point decrease in left ventricular ejection fraction (LVEF) leading to a LVEF below 50%.
timeFrame: Determined at one year follow-up
Secondary outcomes:
measure: Time to first occurrence of hospitalization for heart failure.
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Time to first occurrence of all cause mortality.
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Time to first occurrence of all cause mortality or hospitalization for heart failure.
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Time to first occurrence of atrial fibrillation (AF) de novo.
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: The echocardiographic changes in left ventricular ejection fraction (LVEF) at one year.
timeFrame: Determined at one year follow-up
measure: The echocardiographic changes in diastolic (dys-)function at one year.
timeFrame: Determined at one year follow-up
measure: The occurrence of pacemaker related complications.
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Quality of Life analysis reported as Quality Adjusted Life Years (QALYs)
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Cost effectiveness analysis (CEA)
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
measure: Budget Impact Analysis (BIA)
timeFrame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Gent
country: Belgium
facility: University Hospital Gent
city: Praha
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Rome
country: Italy
facility: Policlinico Casilino
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Kraków
country: Poland
facility: University Hospital Jaegellonian
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Geneva
country: Switzerland
facility: University Hospital of Geneva
Study officials:
affiliation: Department of Cardiology
name: Justin Luermans, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology
name: Kevin Vernooy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: