Safety of Autologous Cord Blood Cells in HLHS Patients During Norwood Heart Surgery

Safety Study of Autologous Cord Blood Stem Cell Treatment in Hypoplastic Left Heart Syndrome Patients Undergoing the Norwood Heart Operation

This study aims to evaluate the safety and feasibility of coronary infusion of autologous placental cord blood mononuclear cells during the Norwood heart operation in newborn hypoplastic left heart syndrome (HLHS) patients.

Study Overview

• Status: Completed
• Conditions: Heart Defects, Congenital; Hypoplastic Left Heart Syndrome; Pediatric Disorder
• Intervention / Treatment: Biological: Autologous Human Placental Cord Blood Mononuclear Cells

Detailed Description

This is a Phase I, open label safety study. Autologous cord blood mononuclear cells (stem cell containing, cord blood buffy coat fraction) was delivered by coronary infusion during the Norwood cardiopulmonary bypass operation in 10 antenatally diagnosed HLHS patients within 2-3 days of birth. Safety and clinical status monitoring was performed to Stage II surgical intervention for HLHS (at approximately 3 months of age). Treated patients will continue to be assessed beyond the trial during follow up between Stage II and III (Fontan) surgical interventions.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 4 days (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and females with antenatally diagnosed Hypoplastic Left Heart Syndrome (all types requiring Norwood operation)
• Written informed consent by parents/legal guardian
• Successful aseptic collection of autologous cord blood unit and transfer of buffy coat mononucleocyte fraction to cold storage pending cardiac surgery within 2-4 days

Exclusion Criteria:

Patient:

• does not have autologous cord blood cells available at the time of cardiopulmonary bypass surgery
• has evidence of arrhythmia requiring anti-arrhythmia therapy
• has an additional congenital diagnosis that contributes to conditions such as an immune system disorder, immune deficiency, complex metabolic disorder, brain dysplasia or progressive neurological degenerative disorder
• has other clinical complexity deemed by the cardiac surgeon to make the patient unsuitable for inclusion in the trial

Mother:

• is serum positive for HIV, hepatitis or other significant pathogen and has known allergies to penicillin, streptomycin or other antibiotic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: hCBMNC; Autologous human placental cord blood mononuclear cells (buffy coat fraction)	Biological: Autologous Human Placental Cord Blood Mononuclear Cells; Autologous human placental cord blood mononuclear cells are infused into the coronary artery during the Norwood heart operation; Other Names: Cord blood buffycoat mononuclear cells, incl stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse cardiac events	Monitoring of adverse events including death, heart or other organ failure, myocardial infarction, sustained/symptomatic ventricular tachycardia, bleeding, stroke	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in right ventricular function -fractional shortening (% units)	Measured by cardiac imaging with serial echocardiography and MRI scans	baseline, 1 month, 3 months, 12 months
Change in right ventricular end-diastolic wall thickness (% units)	Measured by cardiac imaging with serial echocardiography and MRI scans	baseline, 1 month, 3 months, 12 months
Change in right ventricular end-diastolic volume (% units)	Measured by cardiac imaging with serial echocardiography and MRI scans	baseline, 1 month, 3 months, 12 months
Change in right ventricular end-systolic volume (% units)	Measured by cardiac imaging with serial echocardiography and MRI scans	baseline, 1 month, 3 months, 12 months
Increase in body weight	Body weight measured in kilograms	baseline, 1 month, 3 months, 12 months
Composite measure of height and head circumference	Body height and head circumference measured in meters	baseline, 1 month, 3 months, 12 months

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Investigators: Principal Investigator: Salvatore Pepe, Melbourne Children's Campus (incorporating The Royal Children's Hospital, Murdoch Children's Research Institute, the University of Melbourne Department of Paediatrics); Principal Investigator: Christian P Brizard, Melbourne Children's Campus (incorporating The Royal Children's Hospital, Murdoch Children's Research Institute, the University of Melbourne Department of Paediatrics)

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 16, 2018
• Primary Completion (ACTUAL): November 1, 2021
• Study Completion (ACTUAL): June 30, 2022

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (ACTUAL): February 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: heart; cord blood stem cell; congenital; Norwood heart surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Cardiovascular Abnormalities; Syndrome; Congenital Abnormalities; Heart Defects, Congenital; Hypoplastic Left Heart Syndrome
• Other Study ID Numbers: HREC37112A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD may be available following study publication and discussion between CIs and other researchers regarding future multicentre studies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No