HIS-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy

NCT ID: NCT04561778

Last Updated: 2024-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2023-09-30

Brief Summary

This is a randomized, prospective, single-blinded trial to determine the overall rate of successful His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus lead (BVP) to compare acute and mid-term outcomes. Acute outcomes include change in QRS duration pre-and post-pacing (degree of QRS narrowing) and incidence of major periprocedural complications (pericardial tamponade, need for lead revision, etc.). Mid-term outcomes include echocardiographic response at 6 months along with a composite clinical outcome of heart failure hospitalization, ventricular arrhythmias, crossover, and all-cause mortality.

Detailed Description

This is a single-blinded study of 100 patients randomized to a strategy of His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus (CS) lead (BVP). Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HOT-CRT and BVP. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner.

Cross-over is permitted between treatment group allocation if:

CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HOT-CRT.

HOT-CRT subjects may cross-over if His or left bundle pacing lead cannot be positioned with adequate stability and reasonable pacing output, or if optimal QRS narrowing cannot be achieved.

Implant procedure will be per routine percutaneous access, as is standard for pacemaker and Implantable Cardioverter Defibrillators (ICDs). . All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject.

Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 3 and 6 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, and 6 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in Left Ventricular Ejection Fraction (LVEF), chamber dimensions, volumes, and change in Left Ventricular (LV) end systolic volume index as is standard of care in the treatment of patients with advanced heart failure. New York Heart Association (NYHA) functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ 5D) will be assessed pre-implant and at 6 months.

Conditions

Heart Failure，Congestive; Cardiomyopathies; Left Ventricular Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

HOT-CRT

Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used.

Group Type: ACTIVE_COMPARATOR

HOT-CRT

Intervention Type: DEVICE

Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization.

Biventricular Pacing

Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used.

Group Type: ACTIVE_COMPARATOR

Biventricular Pacing

Intervention Type: DEVICE

Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.

Interventions

HOT-CRT

Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization.

Intervention Type: DEVICE

Biventricular Pacing

Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients at least 18 years of age
• Diagnosis is NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy, with at least one of the following:

• LV systolic dysfunction with LVEF ≤ 35% and Evidence of bundle branch block with QRS duration > 120 msec
• LV systolic dysfunction with LVEF ≤ 50% and with need for >40% Right Ventricular (RV) pacing

Exclusion Criteria

• Existing CRT device
• Inability of patient capacity to provide consent for themselves either due to medical or psychiatric comorbidity
• Pregnancy
• Participation in other device trials
• Inability to complete study requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pugazhendhi Vijayaraman

OTHER

Sponsor Role: lead

Responsible Party

Pugazhendhi Vijayaraman

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pugazhendhi Vijayaraman, MD

Role: PRINCIPAL_INVESTIGATOR

Geisinger Clinic

Locations

Geisinger Health

Danville, Pennsylvania, United States

Countries

United States

References

Vijayaraman P, Pokharel P, Subzposh FA, Oren JW, Storm RH, Batul SA, Beer DA, Hughes G, Leri G, Manganiello M, Jastremsky JL, Mroczka K, Johns AM, Mascarenhas V. His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial. JACC Clin Electrophysiol. 2023 Dec;9(12):2628-2638. doi: 10.1016/j.jacep.2023.08.003. Epub 2023 Sep 13.

Reference Type: DERIVED

PMID: 37715742 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2020-0831

Identifier Type: -

Identifier Source: org_study_id