Clinical trial NCT06105580: Conduction System Pacing vs Biventricular Pacing in Systolic Dysfunction and Wide QRS: Mortality, Heart Failure Hospitalization or Cardiac Transplant
Official title: Conduction System Pacing vs Biventricular Resynchronization Therapy in Systolic Dysfunction and Wide QRS: Mortality, Heart Failure Hospitalization or Cardiac Transplant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Resynchronization Therapy
Heart Failure
Keywords: left bundle branch pacing
biventricular pacing
cardiac resynchronization therapy
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Institut d'Investigacions Biomèdiques August Pi i Sunyer
First posted: 2023-10-27
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The first 130 patients have been recruited in the context of the CONSYST I study (ClinicalTrials.gov Identifier: NCT05187611).

It is planned to perform an interim analysis (intermediate analysis) for the primary endpoint in all randomized patients who received intervention. The formal limits of stopping the study will be determined by the limits of futility and effectiveness defined by the rules of sequential stopping using the O'Brien-Fleming method. The interim analysis will be performed with a sample recruitment of 50%. Members of the Data Monitoring Committee, but not any trial investigator, will be informed of the results of the interim analysis. A p of 0.0054 (two-sided alpha) will be required for the interim analysis and 0.049 in the final analysis.
Primary purpose: TREATMENT

Brief summary: Conduction system pacing vs biventricular resynchronization therapy in systolic dysfunction and wide QRS: mortality, heart failure hospitalization or cardiac transplant (CONSYST-CRT II trial).

Superiority trial that aims to study the composite endpoint consisting of all-cause mortality, cardiac transplant or heart failure hospitalization at 12-month follow-up.

Detailed description: To date, studies have shown that conduction system pacing could get similar clinical and echocardiographic responses to those obtained with biventricular therapy.

This study will randomize 320 patients to a strategy of biventricular pacing versus conduction system pacing.

CONSYST-CRT II study will analyze a clinical endpoint as primary endpoint and the following parameters in both groups: left ventricular ejection fraction, ventricular volumes, echocardiographic response (\>=15% decrease in left ventricular end-systolic volume), NYHA functional class, heart failure hospitalization, all-cause mortality, cardiac transplant, QRS shortening, echocardiographic dyssynchrony (atrioventricular, interventricular, intraventricular) and global longitudinal strain.

As a secondary endpoint, baseline predictors of response to conduction system pacing and biventricular pacing according to cardiac magnetic ressonance and electrocardiographic imaging will be studied.

Clinical, electrocardiographic, echocardiographic follow-up will be performed during 12 months.

Eligibility criteria: Inclusion Criteria:

* Patient must indicate acceptance to participate in the study by signing an informed consent document.
* Patient must be ≥ 18 years of age.
* Left bundle branch block, QRS ≥130 and LVEF \<=35%. No indication of stimulation for AV block.
* Non-left bundle branch block, QRS ≥150 and LVEF \<=35%.
* Resynchronization therapy indication for ventricular dysfunction (LVEF \<40%) and indication of cardiac pacing for AV block.
* LVEF \<=35% in NYHA class III or IV, atrial fibrillation and intrinsic QRS \>=130 ms, provided a strategy to ensure biventricular capture is in place.

Exclusion Criteria:

* Myocardial infarction, unstable angina or cardiac revascularization during the previous 3 months.
* Pregnancy.
* Participating currently in a clinical investigation that includes an active treatment.

Primary outcomes:
measure: Composite end-point: all-cause mortality, cardiac transplant or heart failure hospitalization.
timeFrame: 1 year
Secondary outcomes:
measure: Change in left ventricular ejection fraction.
timeFrame: 6 months; 1 year
measure: Change in left ventricular end-systolic volume.
timeFrame: 6 months; 1 year
measure: Echocardiographic response.
timeFrame: 6 months; 1 year
measure: Change in NYHA functional class.
timeFrame: 6 months; 1 year
measure: QRS shortening.
timeFrame: Immediately after the intervention
measure: Correction of septal flash.
timeFrame: 15 days; 6 months; 1 year
measure: Correction of auriculoventricular dyssynchrony.
timeFrame: 15 days; 6 months; 1 year
measure: Correction of interventricular dyssynchrony.
timeFrame: 15 days; 6 months; 1 year
measure: Change in global longitudinal strain (GLS).
timeFrame: 15 days; 6 months; 1 year
measure: Description of baseline predictors of response to conduction system pacing and biventricular pacing. Cardiac fibrosis quantification.
timeFrame: Baseline (pre intervention).
measure: Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Left ventricular activation time (LVAT), ms.
timeFrame: Baseline (pre intervention). And immediately after the intervention
measure: Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Ventricular electrical uncoupling (VEU).
timeFrame: Baseline (pre intervention). And immediately after the intervention
measure: Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Left ventricular dyssynchrony index (LVDI).
timeFrame: Baseline (pre intervention). And immediately after the intervention
measure: Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Conduction velocity (cm/s).
timeFrame: Baseline (pre intervention). And immediately after the intervention
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
Study officials:
affiliation: Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: José Mª Tolosana, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: Margarida Pujol López, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: Lluís Mont, MD, PhD
role: STUDY_CHAIR
References: