A Multi-site Study of Autologous Cord Blood Cells for Hypoxic Ischemic Encephalopathy ((HIE))

A Phase II Multi-site Study of Autologous Cord Blood Cells for Hypoxic (HIE)

This study will test the safety and efficacy of an infusion of a baby's own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.

Study Overview

• Status: Completed
• Conditions: Moderate or Severe Hypoxic-ischemic Encephalopathy in Newborns
• Intervention / Treatment: Biological: Infusion of autologous cord blood; Biological: Placebo

Detailed Description

The purpose of this phase II study is to assess the safety and efficacy of up to two intravenous infusions of autologous volume and red blood cell reduced nucleated umbilical cord blood cells as compared with placebo in neonates with neonatal encephalopathy undergoing hypothermia treatment. Efficacy will be estimated by one year survival and score on Bayley III scores in all three domains equal to or greater than 85. This will be a randomized, double-blind, placebo controlled multi-site trial of up to 160 infants who qualify for cooling.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Gainesville
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • MassGeneral Hospital for Children
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Jacksonville, North Carolina, United States, 32209
      • University of Florida at Jacksonville
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. NICHD Neonatal Research Network Hypothermia Trial inclusion criteria
2. Mothers must have consented or given verbal assent for cord blood collection at delivery, and cord blood must be available for volume and red blood cell reduction before 45 hours of age
3. The infant must be able to receive at least one dose of autologous cord blood before 48 hours of age
4. All infants must have signs of encephalopathy within 6 hours of age

Exclusion Criteria:

1. Major congenital or chromosomal abnormalities
2. Severe growth restriction (birth weight <1800 g)
3. Opinion by attending neonatologist that the study may interfere with treatment or safety of subject
4. Moribund neonates for whom no further treatment is planned
5. Infants born to mothers are known to be HIV, Hepatitis B, Hepatitis C or who have active syphilis or CMV infection in pregnancy
6. Infants suspected of overwhelming sepsis
7. ECMO initiated or likely in the first 48 hours of life

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention cell recipients; Experimental: infusions: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have autologous nucleated cord blood cells available for infusion will receive up to two infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment	Biological: Infusion of autologous cord blood; Infants who meet study enrollment criteria will receive up to 2 infusions of their own volume reduced cord blood cells. The number of doses will be determined by the amount of available cord blood cells.
Placebo Comparator: Placebo recipients; Control: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have cord blood available for infusion will receive placebo (a mix of autologous cord blood red blood cells and plasma) infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment	Biological: Placebo; Infants who meet study enrollment criteria will receive up to 2 placebo infusions composed of an equivalent volume (volume of product that would have been administered if the infant randomized to the intervention arm) of packed red blood cells (PRBCs) from the red cell compartment of the separated cord blood unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at One Year	Number of participants alive at one year.	1 year
Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85	The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate	(Number of participants who died/total number of participants) x 100	1 year
Number of Subjects Who Experience Seizures		During hospitalization, approximately 4-92 days
Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use		During hospitalization, approximately 4-92 days
Number of Subjects Who Require ECMO	ECMO (extracorporeal membrane oxygenation) is a technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life.	During hospitalization, approximately 4-92 days
Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding		During hospitalization, approximately 4-92 days
Number of Subjects Who Are Discharged on Anti-epileptic Medication		At hospital discharge, approximately 4-92 days

Collaborators and Investigators

• Sponsor: Michael Cotten
• Collaborators: The Robertson Foundation

Publications and helpful links

General Publications

• Cotten CM, Murtha AP, Goldberg RN, Grotegut CA, Smith PB, Goldstein RF, Fisher KA, Gustafson KE, Waters-Pick B, Swamy GK, Rattray B, Tan S, Kurtzberg J. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014 May;164(5):973-979.e1. doi: 10.1016/j.jpeds.2013.11.036. Epub 2013 Dec 31.
• Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005 Oct 13;353(15):1574-84. doi: 10.1056/NEJMcps050929.
• Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2017
• Primary Completion (Actual): August 5, 2019
• Study Completion (Actual): August 5, 2019

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: November 20, 2015
• First Posted (Estimate): November 23, 2015

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: newborn infants; Hypoxic-ischemic encephalopathy; autologous cord blood cells
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: Pro00066647

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No