An interventional study of Left ventricular septal pacing and Right ventricular pacing in Cardiac Pacing, Pacing-Induced Cardiomyopathy and Conduction System Pacing, sponsored by Maastricht University. Recruiting at 13 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-15.
Sponsored by Maastricht University · Not applicable, Interventional, and Treatment
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:
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.
117 studies on the registry are indexed under Atrioventricular Block; 43 are open to participants now.
This study's planned enrollment of 470 is above the median of 127 across 78 interventional studies indexed under Atrioventricular Block.
Browse Atrioventricular Block studies →Maastricht University is the lead sponsor of 97 studies on the registry; 20 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Class I or IIa pacemaker indication due to AV conduction disorder
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Implantation of a pacemaker with the ventricular lead placed in the RV.
Procedure: Right ventricular pacing
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.
In the RVP group, the ventricular pacing lead is positioned in the right ventricle.
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.
Time frame: Determined at one year follow-up
Time to first occurrence of hospitalization for heart failure.
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.
Time frame: 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.
All-cause mortality is defined as death from any cause and subdivided into cardiovascular and non-cardiovascular death.
Time frame: 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.
All cause mortality and hospitalization for heart failure are defined as mentioned in secondary outcome 1 and 2.
Time frame: 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.
Occurrence of atrial fibrillation de novo is defined as: Occurrence of a first clinical or subclinical episode of AF as diagnosed respectively by ECG (clinical AF) or by pacemaker interrogation (subclinical AF/atrial high rate episode, lasting \> 24 hours) in patients without a history of AF.
Time frame: 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.
Change in LVEF is based on echocardiography at one year follow-up as compared to baseline echocardiography.
Time frame: Determined at one year follow-up
The echocardiographic changes in diastolic (dys-)function at one year.
Diastolic function will be assessed by determining the following echocardiographic parameters at baseline and one year follow-up: E-wave, A-wave, E/A ratio, e' septal and lateral, E/e', 2D-strain of the left ventricle and atrium, pressure gradient across the tricuspid valve (dPTI) and volume of the left-atrium (LAVI). Diastolic function will be graded according to the current guidelines.
Time frame: Determined at one year follow-up
The occurrence of pacemaker related complications.
Pacemaker (implantation) related complications occurring during pacemaker implantation or during follow-up after pacemaker implantation consisting of: pneumothorax; cardiac tamponade; pocket hematoma requiring re-intervention; pacemaker infection; lead luxation, dislocation, or perforation requiring re-intervention; pacemaker and lead dysfunction during follow-up (elevated threshold/sensing issues/early battery depletion) requiring re-intervention.
Time frame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
Quality of Life analysis reported as Quality Adjusted Life Years (QALYs)
Quality of life will be analyzed using the EQ-5D-5L questionnaire at baseline, 6 and 12 months follow-up and every 6 months thereafter.
Time frame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
Cost effectiveness analysis (CEA)
A trial based economical evaluation from a societal perspective will be performed in accordance with the Dutch guidelines for economical evaluations in healthcare. Resource use will be measured from a societal perspective using data from case record forms and the Medical Consumption (MCQ) and Productivity loss (PCQ) questionnaires.
Time frame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
Budget Impact Analysis (BIA)
Budget impact analysis will be performed from a societal, health care provider and health care insurer perspective. The eligible population will be estimated based on national health care data. Costs of the intervention and heart failure costs will be included. Indirect costs will not be included. The time horizon will be 3 years. The expected uptake rate will be estimated based on a panel of experts (cardiologists, implementation specialist, patient representatives) and analyses will be performed for this expected uptake rate and several slightly higher and lower uptake rates. Uncertainties and scenarios will be discussed in a panel of experts as well and different scenarios will be analysed. Recommendations of the ISPOR task force are followed for all BIA calculations.
Time frame: Determined at the end of the follow-up period (when the last-included patient reached the one year follow-up period)
Plan to share: No
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Started May 2021 (actual). Primary completion is estimated for May 2025, 48 months after the start.
Of 44 interventional studies with no phase under Atrioventricular Block, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 55. This study's planned 48 months is above that.
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