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

Cardiomyopathies Clinical Trial

— HOT-CRT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04561778
• Other study ID #: 2020-0831
• Status: Completed
• Phase: N/A
• Start date: April 15, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: November 2023
• Source: Geisinger Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 30, 2023
• Est. primary completion date: May 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Heart Failure
• Heart Failure,Congestive
• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Geisinger Health	Danville	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pugazhendhi Vijayaraman

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in left ventricular ejection fraction	change in LVEF measured by 2D echo at 6 months compared to baseline	6 months
Primary	Freedom from major complications or need for CRT lead revision	complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming	6 months
Secondary	Heart failure hospitalization (HFH)	Heart failure hospitalization is defined as an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy.	6 months
Secondary	Ventricular tachycardia or ventricular fibrillation requiring ICD therapy	ventricular tachycardia or ventricular fibrillation that required ICD therapy such as anti-tachycardia pacing or shock	6 months
Secondary	Crossover of treatment from HOT-CRT to BVP or BVP to HOT-CRT	Failure to implant His bundle or left bundle pacing lead requiring cross over to coronary sinus lead; failure to implant coronary sinus lead necessitating cross-over to His bundle or left bundle pacing lead	6 months
Secondary	Change in NYHA functional class	Functional class change at 6 months compared to baseline.	6 months
Secondary	Change in QRS duration	QRS duration at final programmed configuration between the 2 groups will be compared at implant and at 6 month follow-up	6 months
Secondary	Change in LV end-systolic volume index	15% or more increase in LV end-systolic volume index at 6 months compared to baseline.	6 months
Secondary	Composite endpoint of death, HFH, ventricular arrhythmias or crossover	Time to combined endpoint of death, HFH, VA or crossover.	6 months
Secondary	Change in quality of life (QOL)scores	Change in QOL measured by the Kansas City Cardiomyopathy Questionnaire at 6 months compared to baseline. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	6 months
Secondary	Change in quality of life (QOL)scores	Change in QOL measured by EuroQol-5D at 6 months compared to baseline. Scores on each of 5 patient reported dimensions are converted to a single utility index using country specific value sets. Additionally, a visual analog scale from 0-100, in which higher score reflects better health status.	6 months