LVSP vs RVP in Patients With AV Conduction Disorders

NCT04595487 | Recruiting DMC

• 1 other identifier: NL72047.068.20
• Study Type: interventional
• Target: 470
• Locations: 7 countries
• Sites: 13

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.

Conditions

Cardiac Pacing; Pacing-Induced Cardiomyopathy; Conduction System Pacing; Left Ventricular Septal Pacing; Atrioventricular Block

Outcome Measures

Primary Outcomes (1)

• 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%.

  Hospitalization for heart failure is defined as: 1. hospitalization or unplanned hospital visits for heart failure requiring intravenous diuretics and/or (adjustment of) other medical heart failure therapy; 2. hospitalization for upgrade to cardiac resynchronization therapy (CRT, ie biventricular pacing) for progression of heart failure with worsening NYHA class and/or (increased) need for diuretic therapy or other medical heart failure therapy; 3. or hospitalization for upgrade to CRT for developing a class I indication for CRT (includes symptomatic heart failure); 4. or hospitalization or unplanned hospital visit for heart failure triggered by an episode of atrial fibrillation with uncontrolled heart rate requiring intravenous diuretics or adjustment of rate control therapy. All-cause mortality is defined as death from any cause and subdivided into cardiovascular and non-cardiovascular death.

  Determined at one year follow-up

Secondary Outcomes (10)

• Time to first occurrence of hospitalization for heart failure.

  Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)

• Time to first occurrence of all cause mortality.

  Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)

• Time to first occurrence of all cause mortality or hospitalization for heart failure.

  Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)

• Time to first occurrence of atrial fibrillation (AF) de novo.

  Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)

• The echocardiographic changes in left ventricular ejection fraction (LVEF) at one year.

  Determined at one year follow-up

Study Arms (2)

left ventricular septal pacing

EXPERIMENTAL

Implantation of a pacemaker with the ventricular lead delivered transvenously through the interventricular septum (IVS) to the left ventricular (LV) septum.

Procedure: Left ventricular septal pacing

right ventricular pacing

ACTIVE COMPARATOR

Implantation of a pacemaker with the ventricular lead placed in the RV.

Procedure: Right ventricular pacing

Interventions

Left ventricular septal pacing PROCEDURE

In the LVSP group, instead of placing the standard RV lead, the commercially available 3830 Select Secure (Medtronic, Minneapolis, USA) lead is introduced via standard transvenous approach and positioned against the right ventricular side of the IVS by using the commercially available non-deflectable septal delivery sheath (C315, Medtronic, Minneapolis, USA) under fluoroscopic guidance. Subsequently this pacing lead is advanced/screwed through the interventricular septum until the left ventricular septum is reached. Accurate lead position at the left ventricular septum will be determined anatomically using fluoroscopy, and electrically by evaluating local electrograms and changes in paced electrocardiogram morphology. In case of unsuccessful lead positioning in the left ventricular septum, the Select Secure lead may be placed at the His bundle region (natural conduction system of the heart) or in the right ventricle according to the physician's discretion.

left ventricular septal pacing

Right ventricular pacing PROCEDURE

In the RVP group, the ventricular pacing lead is positioned in the right ventricle.

right ventricular pacing

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Medtronic: collaborator

Study Sites (13)

Ziekenhuis Oost Limburg

Genk, Belgium

NOT YET RECRUITING

University Hospital Gent

Ghent, Belgium

NOT YET RECRUITING

University Hospital Kralovske Vinohrady

Prague, Czechia

RECRUITING

Policlinico Casilino

Rome, Italy

NOT YET RECRUITING

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

RECRUITING

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

RECRUITING

Reinier de Graaf Gasthuis

Delft, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, Netherlands

RECRUITING

Medisch Spectrum Twente

Enschede, Netherlands

RECRUITING

Sint Antonius Ziekenhuis

Nieuwegein, Netherlands

RECRUITING

University Hospital Jaegellonian

Krakow, Poland

NOT YET RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, Spain

NOT YET RECRUITING

University Hospital of Geneva

Geneva, Switzerland

NOT YET RECRUITING

MeSH Terms

Conditions

Atrioventricular Block

Condition Hierarchy (Ancestors)

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

Study Officials

• Justin Luermans, MD PhD

  Department of Cardiology

  PRINCIPAL INVESTIGATOR

• Kevin Vernooy, MD PhD

  Department of Cardiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Justin Luermans, MD PhD

CONTACT

+31433875093; justin.luermans@mumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 20, 2020
• Study Start: May 1, 2021
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: April 15, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); ES (1); CH (1); CZ (1); NL (6); BE (2); IT (1)