LEft VEntricuLar Activation Time Shortening With Physiological Pacing vs Biventricular Resynchronization Therapy (LEVEL-AT)

LEft VEntricuLar Activation Time Shortening With Physiological Pacing vs Biventricular Resynchronization Therapy: a Randomized Study (LEVEL-AT)

The LEVEL-AT Trial (LEft VEntricuLar Activation Time Shortening with Physiological Pacing vs Biventricular Resynchronization therapy: a randomized study) is a non-inferiority study that aims to determine if physiological pacing could decrease the left ventricular activation time compared with biventricular therapy.

Study Overview

• Status: Completed
• Conditions: Physiological Pacing; Resynchronization Therapy
• Intervention / Treatment: Device: Lead placed in the His-Purkinje system in order to achieve QRS shortening.; Device: Lead is placed in a tributary of the coronary sinus.

Detailed Description

To date studies have showed that physiological pacing could get similar clinical and echocardiographic response to that obtained with biventricular therapy. Activation time shortening with permanent physiological pacing has not been studied.

This study will randomize 70 patients to a strategy of: biventricular pacing versus physiological pacing.

LEVEL-AT study will analyze the following parameters in the 2 groups: shortening of the QRS, activation time with electrocardiographic imaging, echocardiographic asynchrony and ventricular function and clinical parameters (NYHA functional class, mortality and heart failure hospitalization).

Clinical, electrocardiographic, echocardiographic and electrocardiographic imaging follow-up will be performed for 1 year.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Select
    • Barcelona, Select, Spain, 08036
      • Hospital Clinic de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient must indicate their acceptance to participate in the study by signing an informed consent document.
• The patient must be ≥ 18 years of age.
• Left bundle branch block, QRS ≥130 and FEVI <=35% (Indication of cardiac resynchronization IA or IB ESC Guidelines). No indication of stimulation for AV block.
• Patients with indication of resynchronization therapy for ventricular dysfunction and indication of cardiac stimulation for AV block according to ESC Guidelines (IA ESC Guidelines).
• Non-left bundle branch block, QRS ≥150 and FEVI <=35% (Indication of cardiac resynchronization IIaB ESC Guidelines).

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Physiological pacing; Pacing the his-purkinje system. Crossover to biventricular CRT will be allowed in the following situations: failed physiological pacing lead implantation; high thresholds (>3.5V / 1ms); no shortening of QRS (shortening <20%) or failure to meet non-selective HBP criteria [Europace. 2019 Oct 9. doi: 10.1093/europace/euz275].	Device: Lead placed in the His-Purkinje system in order to achieve QRS shortening.; Physiologic pacing to achieve QRS shortening. If the patient has indication of stimulation (AV block), a backup lead will be implanted in the right ventricle. All patients will have a lead placed in the right atrium (except those that have permanent atrial fibrillation).
Active Comparator: Biventricular resynchronization therapy; Pacing from the right ventricular and coronary sinus leads. Electrocardiographic optimization with fusion-optimized intervals. Crossover from biventricular CRT to physiological pacing will be allowed in the following situations: coronary sinus cannot be cannulated; no lateral or posterolateral branches; or phrenic stimulation.	Device: Lead is placed in a tributary of the coronary sinus.; Biventricular Resynchronization Therapy is the use of a pacemaker with two endocardial leads placed in the right atrium and right ventricle. The third lead is placed in a tributary of the coronary sinus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular activation time.	Left ventricular activation time measured by eletrocardiographic imaging.	45 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QRS duration.	QRS duration (milliseconds) measured with a 12-lead ECG.	Implant, 6 months and 12 months.
Left ventricular activation time.	Left ventricular activation time measured by eletrocardiographic imaging	6 months and 12 months.
Change in left ventricular function.	Left ventricular ejection fraction measured with Simpson method with echocardiography.	6 months and 12 months.
Change in end-systolic volume.	End-systolic volume measured with echocardiography.	6 months and 12 months.
Change in NYHA functional class.	NYHA functional class I, II, III, IV.	6 months and 12 months.
Hospitalization due to heart failure or mortality (combined endpoint).	Hospitalization: patient hospitalization (yes/no) Mortality: mortality (yes/no)	1 year.
Correction of septal flash	Correction of septal flash determined with echocardiography (M mode)	15 days

Collaborators and Investigators

• Sponsor: Josep Lluis Mont Girbau
• Collaborators: Institut d'Investigacions Biomèdiques August Pi i Sunyer; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV)
• Investigators: Principal Investigator: Jose M Tolosana, MD, PhD, Hospital Clinic of Barcelona; Principal Investigator: Margarida Pujol Lopez, MD, Hospital Clinic of Barcelona; Study Director: Lluis Mont Girbau, MD, PhD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Physiological pacing; Resynchronization therapy; Electrocardiographic imaging
• Other Study ID Numbers: LEVEL-AT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes