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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)

Phase 1
Not yet recruiting
Conditions
Hypoplastic Left Heart Syndrome
Interventions
Drug: Ventrix Bio Extracellular Matrix
Registration Number
NCT06461676
Lead Sponsor
Emory University
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
12
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ventrix Bio Extracellular MatrixVentrix Bio Extracellular MatrixTreatment intervention of a total of 8 injections into the right ventricle of the heart will occur before the patient comes off of the heart-lung bypass machine used during the Stage II Glenn Operation. The treatment will be conducted according to clinical guidelines set in place while the patient is undergoing a surgical intervention before the patient comes off the heart/lung bypass machine required for the stage II Glenn Procedure.
Primary Outcome Measures
NameTimeMethod
Number of Cardiogenic shock eventsDay 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 ventricular tachycardia eventsupto 30 days post operation

Number of sustained/symptomatic ventricular tachycardia incidences requiring intervention with inotropic support or anti-arrhythmics

Number of Adverse Eventsupto 30 days post operation

Number of adverse events occurring post op

Number of deathsupto 30 days post operation

Number of deaths occurring post op

Number of VentriGel products manufactured and delivered to subjects12 months
Number of patients receiving Cardiac MRIsBaseline, 6 months, 12 months
Number of unplanned cardiovascular operation events30 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 pacemakerupto 30 days post operation

Number of patients requiring new permanent pacemaker

Stroke or embolic eventupto 30 days post operation

Stroke or embolic event to the brain determined by CT scan

Secondary Outcome Measures
NameTimeMethod
Change in right ventricular global circumferential strainBaseline, 6 months,12 months post operation

This will be measured by serial transthoracic echocardiogram (TTE)

Change in right ventricular end diastolic volumeBaseline, 6 months, 12 months post operation

This will be measured by serial echocardiograms and MRI scans

Change in tricuspid regurgitationBaseline, 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 global longitudinal strainBaseline, 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 ventricular ejection fractionBaseline, 6 months, 12 months post operation

This will be measured by serial echocardiograms and MRI scans

Change in right ventricular function Fractional Area ChangeBaseline, 6 months,12 months post operation

This will be measured by serial transthoracic echocardiogram (TTE)

Change in right ventricular end systolic volumeBaseline, 6 months, 12 months post operation

This will be measured by serial echocardiograms and MRI scans

Change in right atrial volume indexedBaseline, 6 months,12 months post operation

This will be measured by serial transthoracic echocardiogram (TTE)

Trial Locations

Locations (1)

Children's Healthcare of Altanta

🇺🇸

Atlanta, Georgia, United States

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