Hydrogen In Neonatal Encephalopathy (HIE) Trial

NCT07411911 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-P00052510
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hypoxic-Ischemic Encephalopathy; HIE

Keywords

Hypoxic-Ischemic Encephalopathy; HIE; Hydrogen Gas; Neonates; Brain Injury

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Evidence of Brain Injury on Clinically Ordered Imaging

  3-7 days post randomization

• Markers of Ischemic Injury

  0, 1, 2, 3, and 4 days post randomization

• Survival

  post-randomization through 6 months of age

• Neurodevelopmental Outcome

  24-36 months of age

Study Arms (2)

Hydrogen Gas (H2) Intervention

EXPERIMENTAL

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)

Standard of Care

NO INTERVENTION

Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with no study intervention

Interventions

Hydrogen Gas (H2) DRUG

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.

Hydrogen Gas (H2) Intervention

Eligibility Criteria

• Age: Up to 2 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants born ≥36 weeks gestation.
• Any one of the following:
• sentinel event prior to delivery, such as uterine rupture, profound fetal bradycardia, or cord prolapse
• low Apgar scores (≤ 5 at 10 minutes of life)
• prolonged resuscitation at birth (chest compressions and/or intubation and/or mask ventilation at 10 minutes)
• severe acidosis (pH \< 7.0 from cord or neonate blood gas within 60 minutes of birth)
• abnormal base excess (≤ -16 mEq/L from cord gas or neonate blood gas within 60 minutes of birth)
• Moderate or severe encephalopathy present in the first 2 hours of life.
• Intubated and mechanically ventilated at the time of enrollment.

You may not qualify if:

• Enrollment in the opt-out program.
• Presence of known cyanotic congenital heart disease.
• Presence of known or suspected genetic/chromosomal syndrome or multiple congenital anomalies.
• 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.
• Presence of antenatally diagnosed central nervous system malformation, including hemorrhage, hydrocephalus, or structural anomaly of the brain (eg. polymicrogyria).
• Need for high frequency ventilation (HFV) at time of enrollment.
• Patients receiving respiratory support via Drager Babylog ventilators.
• Study enrollment and randomization after 2 hours of age

Sponsors & Collaborators

• Boston Children's Hospital: lead

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Brain Injuries

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Brian Kalish, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa Young, MS, BA, RN

CONTACT

617-355-8330; Vanessa.young@childrens.harvard.edu

Rylee Kerper, MPH

CONTACT

617-919-7355; rylee.kerper@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatologist, Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: February 17, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2031
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share