Hydrogen In Neonatal Encephalopathy (HIE) Trial

February 9, 2026 updated by: Brian Kalish, Boston Children's Hospital
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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
54

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Hydrogen Gas Adminstration Safety
Time Frame: 30 days post randomization
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
Time Frame: 72 hours post randomization
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evidence of Brain Injury on Clinically Ordered Imaging
Time Frame: 3-7 days post randomization
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
Time Frame: 0, 1, 2, 3, and 4 days post randomization
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
Time Frame: post-randomization through 6 months of age
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
Time Frame: 24-36 months of age
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boston Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Brian Kalish, MD, Boston Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 17, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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