Study of Intramyocardial Injection of Ventrix Bio Extracellular Matrix (VentriGel) to Assess the Safety and Feasibility in Pediatric Patients With Hypoplastic Left Heart Syndrome (HLHS)

Hypoplastic Left Heart Syndrome Clinical Trial

Official title:

Study of Intramyocardial Injection of Ventrix Bio Extracellular Matrix (VentriGel) to Assess the Safety and Feasibility in Pediatric Patients With Hypoplastic Left Heart Syndrome (HLHS)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06461676
• Other study ID #: STUDY00006965
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: October 1, 2024
• Est. completion date: September 30, 2027

Study information

• Verified date: June 2024
• Source: Emory University
• Contact: William Mahle, MD
• Phone: 404-256-2593
• Email: MahleW[@]kidsheart.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this Phase I Open-Label study is to demonstrate the safety and feasibility of VentriGel injection in children with Hypoplastic Left Heart Syndrome (HLHS). The main questions it aims to answer are: - Whether VentriGel is safe in treating patients with HLHS - Whether there are any preliminary improvements in measures of cardiac function following Ventrigel injection

Description:

HLHS, a type of congenital heart disease, presents a unique challenge where the left ventricle fails to develop, necessitating the right ventricle to manage both systemic and pulmonary blood flow. This condition, once fatal, has become manageable due to advancements in surgical techniques, with reported 5-year survival rates of 70-90%. However, these staged procedures, while lifesaving, can strain the right ventricle, leading to long-term issues such as weakened muscle and reduced cardiac function. Additionally, even with surgical intervention, patients often face a diminished quality of life. Addressing these challenges, ongoing clinical trials explore regenerative therapies, particularly stem cell injections, aiming to improve heart function. Yet, concerns persist regarding the practicality and efficacy of these treatments, including issues with cell survival and coordination of injections within narrow timeframes. Innovatively, the investigator and the team propose an alternative approach using VentriGel, an injectable hydrogel derived from decellularized porcine myocardium. Originally designed for treating heart failure post-myocardial infarction in adults, VentriGel has shown promising results in animal models, demonstrating significant improvements in cardiac function. Notably, its shelf-stable nature and flexible timing for administration offer advantages over traditional stem cell therapies. Moreover, VentriGel's effectiveness in addressing right-ventricular failure, as demonstrated in recent studies, highlights its potential as a solution for HLHS patients. Leveraging approved extracellular matrix devices, such as Alloderm and SurgiSIS, further underscores the feasibility and safety of this approach, paving the way for potentially transformative treatments in congenital heart diseases.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Year

Eligibility

Inclusion Criteria:

• Subjects with Hypoplastic Left Heart Syndrome (HLHS) requiring Stage II Glenn operation under one year of age

Exclusion Criteria:

• Subjects undergoing the Stage II Glenn operations who do not have HLHS
• Subjects requiring mechanical circulatory support within 5 days pre pre-surgical intervention
• Parent or guardian unwilling or unable to comply with necessary follow-up(s)
• Immunosuppressive diseases or subjects who require treatment with interventions that cause immunosuppression
• A history of tumor or malignancy
• Coagulation disorders
• Chromosomal abnormalities that limit expected survival to < 1 year
• Abnormal lab values that may increase the risk of the study procedure (WBC >20,000 cells/ul or < 1,000 cells/ul; platelet count < 50,000 cells/ul; Hgb < 8.0 gm/dl; LFTs > 2x reference lab upper limit of normal) at the time of screening
• Subjects with conduction abnormalities, including atrioventricular block and bundle branch blocks
• Ventricular arrhythmias due to antiarrhythmic pharmacological therapy

Related Conditions & MeSH terms

• Hypoplastic Left Heart Syndrome
• Syndrome

Intervention

Drug:
• Ventrix Bio Extracellular Matrix
VentriGel will be administered by injection into the right ventricle of the heart in the following defined doses per injection. There will be a total of 8 injections. The proposed dose of up to 0.6 mL is administered as up to 8 sequential injections of 4 injections of 0.1 mL each and 4 injections of 0.05 mL each.

Locations

Country	Name	City	State
United States	Children's Healthcare of Altanta	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	University of California, San Diego, Ventrix, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of ventricular tachycardia events	Number of sustained/symptomatic ventricular tachycardia incidences requiring intervention with inotropic support or anti-arrhythmics	upto 30 days post operation
Primary	Number of Cardiogenic shock events	Cardiogenic shock (i.e. tissue hypoperfusion presented by hypotension due to decreased cardiac output, determined by rising lactate levels (5x normal levels in first 24 hours, 2.5x normal levels in first 30 days)	Day 1, 30 days post operation
Primary	Number of unplanned cardiovascular operation events	Unplanned cardiovascular operation due to right ventricular intramyocardial injection site bleeding in the first 5 days after Stage II operation decreased cardiac output, determined by rising lactate levels (5x normal levels in first 24 hours, 2.5x normal levels in first 30 days)	30 days post operation
Primary	Number of patients requiring new permanent pacemaker	Number of patients requiring new permanent pacemaker	upto 30 days post operation
Primary	Stroke or embolic event	Stroke or embolic event to the brain determined by CT scan	upto 30 days post operation
Primary	Number of Adverse Events	Number of adverse events occurring post op	upto 30 days post operation
Primary	Number of deaths	Number of deaths occurring post op	upto 30 days post operation
Primary	Number of VentriGel products manufactured and delivered to subjects		12 months
Primary	Number of patients receiving Cardiac MRIs		Baseline, 6 months, 12 months
Secondary	Change in right ventricular ejection fraction	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Secondary	Change in right ventricular end diastolic volume	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Secondary	Change in right ventricular end systolic volume	This will be measured by serial echocardiograms and MRI scans	Baseline, 6 months, 12 months post operation
Secondary	Change in tricuspid regurgitation	This will be measured by serial echocardiograms and MRI scans. tricuspid regurgitation measured by tricuspid valve vena contracta width	Baseline, 6 months,12 months post operation
Secondary	Change in right ventricular function Fractional Area Change	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Secondary	Change in right ventricular global longitudinal strain	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Secondary	Change in right ventricular global circumferential strain	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Secondary	Change in right ventricular Tricuspid Annular Plane Systolic Excursion (TAPSE)	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation
Secondary	Change in right atrial volume indexed	This will be measured by serial transthoracic echocardiogram (TTE)	Baseline, 6 months,12 months post operation