Hydrogen In Neonatal Encephalopathy (HIE) Trial

Despite advances in neonatal care, moderate-to-severe acute perinatal HIE in late preterm and term infants remains a cause of mortality, neurological injury, and long-term neurodevelopmental disability. The current standard of care includes therapeutic hypothermia for 72 hours, but 40-50% of infants will die or suffer significant neurodevelopmental impairment. It has been shown that administration of hydrogen gas (H2) significantly diminishes ischemic injury in swine, and that H2 administration at the dose and duration proposed herein is well-tolerated in healthy adults. The purpose of this project is to test the feasibility and safety of H2 administration as an adjunct to therapeutic hypothermia in infants with HIE. Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with or without the administration of 2% hydrogen in gases administered via the ventilator, non-invasive ventilation, or nasal cannula for 72 hours.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypoxic-Ischemic Encephalopathy; HIE
• Intervention / Treatment: Drug: Hydrogen Gas (H2)

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vanessa Young, MS, BA, RN; Phone Number: 617-355-8330; Email: Vanessa.young@childrens.harvard.edu
• Study Contact Backup: Name: Rylee Kerper, MPH; Phone Number: 617-919-7355; Email: rylee.kerper@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Infants born ≥36 weeks gestation.

2. Any one of the following:

   1. sentinel event prior to delivery, such as uterine rupture, profound fetal bradycardia, or cord prolapse
   2. low Apgar scores (≤ 5 at 10 minutes of life)
   3. prolonged resuscitation at birth (chest compressions and/or intubation and/or mask ventilation at 10 minutes)
   4. severe acidosis (pH < 7.0 from cord or neonate blood gas within 60 minutes of birth)
   5. abnormal base excess (≤ -16 mEq/L from cord gas or neonate blood gas within 60 minutes of birth)
3. Moderate or severe encephalopathy present in the first 2 hours of life.
4. Intubated and mechanically ventilated at the time of enrollment.

Exclusion Criteria:

1. Enrollment in the opt-out program.
2. Presence of known cyanotic congenital heart disease.
3. Presence of known or suspected genetic/chromosomal syndrome or multiple congenital anomalies.
4. Presence of known congenital malformation that is expected to require urgent surgical intervention in the neonatal period, including congenital diaphragmatic hernia (CDH), gastroschisis, omphalocele, intestinal atresia, or imperforate anus.
5. Presence of antenatally diagnosed central nervous system malformation, including hemorrhage, hydrocephalus, or structural anomaly of the brain (eg. polymicrogyria).
6. Need for high frequency ventilation (HFV) at time of enrollment.
7. Patients receiving respiratory support via Drager Babylog ventilators.
8. Study enrollment and randomization after 2 hours of age

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrogen Gas (H2) Intervention; Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with the administration of 2% hydrogen in gases administered via the ventilator, non-invasive ventilation, or nasal cannula for 72 hours	Drug: Hydrogen Gas (H2); Patients randomized to the hydrogen group will receive 2% hydrogen gas incorporated into all gas mixtures for 72 hours. The hydrogen gas will be administered via the ventilator, non-invasive ventilation, or nasal cannula.
No Intervention: Standard of Care; Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with no study intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hydrogen Gas Adminstration Safety	The incidence rate of Study AEs per day during the first 30 days post-randomization that have been classified as treatment-related or possibly treatment-related will be tracked.	30 days post randomization
Hydrogen Gas Adminstration Feasibility	To establish the feasibility of H2 administration in infants with HIE, we will compute the percentage of the first 72 hours (starting at the time of randomization) in which H2 gas was administered	72 hours post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of Brain Injury on Clinically Ordered Imaging	Using brain imaging collected after therapeutic hypothermia has completed, we will assess if H2 therapy minimizes ischemic changes	3-7 days post randomization
Markers of Ischemic Injury	Clinically ordered laboratory values will be analyzed in order to explore whether H2 therapy diminishes changes in routine laboratory markers of ischemic injury after HIE.	0, 1, 2, 3, and 4 days post randomization
Survival	Participant survival to hospital discharge, as well as NICU and hospital lengths of stay will be tracked in order to assess whether H2 therapy improves overall survival rate.	post-randomization through 6 months of age
Neurodevelopmental Outcome	The Bayley Scales of Infant and Toddler Development-4 (Bayley-4) will be used to explore whether H2 therapy improves neurodevelopmental outcome. Neurodevelopmental impairment Bayley-4 cognitive or motor score of less than 90.	24-36 months of age

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Brian Kalish, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Brain Injury; HIE; Neonates; Hypoxic-Ischemic Encephalopathy; Hydrogen Gas
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Brain Ischemia; Signs and Symptoms, Respiratory; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia, Brain; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: IRB-P00052510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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