Hydrogen In Neonatal Encephalopathy (HIE) Trial

Phase 1Not Yet RecruitingNCT07411911

Boston Children's Hospital54 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

HIE Hypoxic-Ischemic Encephalopathy

Interventions

Eligibility

Sex: ALLMax age: 2 Hours

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 72 hours post randomization

Secondary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 24-36 months of age