HIEPhase 1NCT07411911
Hydrogen In Neonatal Encephalopathy (HIE) Trial
A Phase 1 study testing Hydrogen Gas (H2) in people with HIE and Hypoxic-Ischemic Encephalopathy, run by Boston Children's Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 2 hours
- Conditions the study is for
- HIE, Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Hydrogen Gas (H2)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- Mar 2026to Mar 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
- HIE, Hypoxic-Ischemic Encephalopathy
- Being tested
- Hydrogen Gas (H2)
- Keywords
- Hypoxic-Ischemic Encephalopathy, HIE, Hydrogen Gas, Neonates, Brain Injury
- Medical subject headings
- Hypoxia-Ischemia, Brain, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 72 hours post randomization
Secondary outcomes (4)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24-36 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study startMar 2026 (estimated)
- Primary completionMar 2028 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIEStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Kalish, Boston Children's Hospital
- Investigators
- Brian Kalish, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07411911
- Sponsor's protocol ID
- IRB-P00052510
- Status last verified
- Feb 2026
- First submitted
- 25 Nov 2025
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrogen In Neonatal Encephalopathy (HIE) Trial
- ClinicalTrials.gov ID
- NCT07411911
- Acronym / sponsor ID
- IRB-P00052510
- Conditions
- HIE, Hypoxic-Ischemic Encephalopathy
- Keywords
- Hypoxic-Ischemic Encephalopathy, HIE, Hydrogen Gas, Neonates, Brain Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Mar 2026 (estimated)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydrogen Gas (H2) Intervention | Experimental | Drug: Hydrogen Gas (H2)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 |
| 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 |
Who may qualify
- Ages
- Up to 2 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Infants born ≥36 weeks gestation.
- Any one of the following:
- Moderate or severe encephalopathy present in the first 2 hours of life.
- Intubated and mechanically ventilated at the time of enrollment.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Hydrogen Gas (H2) Intervention |
Primary outcome
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.
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
4 secondary outcomes
Evidence of Brain Injury on Clinically Ordered Imaging
Time frame: 3-7 days post randomization
Markers of Ischemic Injury
Time frame: 0, 1, 2, 3, and 4 days post randomization
Survival
Time frame: post-randomization through 6 months of age
Neurodevelopmental Outcome
Time frame: 24-36 months of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Kalish, MD principal investigator
Boston Children's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydrogen Gas (H2) in people with HIE and Hypoxic-Ischemic Encephalopathy, run by Boston Children's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanessa Young, MS, BA, RN (617-355-8330, Vanessa.young@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hydrogen Gas Adminstration Safety (time frame: 30 days post randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.