Hypoplastic Left Heart Syndrome
Conditions
Keywords
Stage II Glenn operation, HLHS
Brief 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
Detailed 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.
Interventions
DRUGVentrix 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.
Sponsors
Ventrix, Inc.
University of California, San Diego
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients receiving Cardiac MRIs | Baseline, 6 months, 12 months | — |
| Number of ventricular tachycardia events | upto 30 days post operation | Number of sustained/symptomatic ventricular tachycardia incidences requiring intervention with inotropic support or anti-arrhythmics |
| Number of Cardiogenic shock events | Day 1, 30 days post operation | 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) |
| Number of unplanned cardiovascular operation events | 30 days post operation | 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) |
| Number of patients requiring new permanent pacemaker | upto 30 days post operation | Number of patients requiring new permanent pacemaker |
| Stroke or embolic event | upto 30 days post operation | Stroke or embolic event to the brain determined by CT scan |
| Number of Adverse Events | upto 30 days post operation | Number of adverse events occurring post op |
| Number of deaths | upto 30 days post operation | Number of deaths occurring post op |
| Number of VentriGel products manufactured and delivered to subjects | 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in right ventricular ejection fraction | Baseline, 6 months, 12 months post operation | This will be measured by serial echocardiograms and MRI scans |
| Change in right ventricular end diastolic volume | Baseline, 6 months, 12 months post operation | This will be measured by serial echocardiograms and MRI scans |
| Change in right ventricular end systolic volume | Baseline, 6 months, 12 months post operation | This will be measured by serial echocardiograms and MRI scans |
| Change in tricuspid regurgitation | Baseline, 6 months,12 months post operation | This will be measured by serial echocardiograms and MRI scans. tricuspid regurgitation measured by tricuspid valve vena contracta width |
| Change in right ventricular function Fractional Area Change | Baseline, 6 months,12 months post operation | This will be measured by serial transthoracic echocardiogram (TTE) |
| Change in right ventricular global longitudinal strain | Baseline, 6 months,12 months post operation | This will be measured by serial transthoracic echocardiogram (TTE) |
| Change in right ventricular global circumferential strain | Baseline, 6 months,12 months post operation | This will be measured by serial transthoracic echocardiogram (TTE) |
| Change in right ventricular Tricuspid Annular Plane Systolic Excursion (TAPSE) | Baseline, 6 months,12 months post operation | This will be measured by serial transthoracic echocardiogram (TTE) |
| Change in right atrial volume indexed | Baseline, 6 months,12 months post operation | This will be measured by serial transthoracic echocardiogram (TTE) |
Countries
United States
Contacts
Primary ContactWilliam Mahle, MD
Outcome results
None listed