Hypoxic Ischaemic Encephalopathy
Conditions
Keywords
Xenon, Hypothermia, Hypoxic Ischemic Encephalopathy, Newborn, Neonate, Term, Neuroprotection, Cooling, HIE
Brief summary
This study examines the effect of inhaled xenon gas in the treatment of newborn infants with hypoxic-ischemic encephalopathy (HIE) in combination with cooling, which is the standard treatment for this condition. The hypothesis is that the xenon + cooling combination will produce better neuroprotection than the standard treatment of cooling alone.
Interventions
DRUGXenon gas
Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.
OTHERWhole body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment), including during transport for outborn babies, starting within 3 hours after birth.
Sponsors
University of Bristol
University Hospitals Bristol and Weston NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Infants will be eligible for for the trial if the St Michael's hospital standard inclusion criteria for cooling and additional inclusion criteria for xenon administration are met. St Michael's hospital standard inclusion criteria for standard hypothermia treatment of 72 hrs: A: Neonates born at greater than 36 weeks gestation (estimated or clinical assessment) with at least ONE of the following: 1. Apgar score of ≤5 at ten minutes after birth 2. Continued need for resuscitation, including tracheal or mask ventilation, at ten minutes after birth 3. Acidosis, defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less \< 7.00 4. Base deficit ≥16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood). If the infant meets criterion A then assess for neurological abnormality using criterion B and C (by trained personnel): B: Moderate or Severe encephalopathy as evidenced by any of the following: 1. Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive and at least ONE or more of the following: 2. Hypotonia 3. Abnormal reflexes including oculomotor or pupillary abnormalities 4. Absent or weak suck 5. Clinical seizures, as recorded by trained personnel And C: At least 30 minutes duration of amplitude-integrated electroencephalography (aEEG) recording that shows abnormal background aEEG activity. The decision to cool is based on the worst 30 min section of the aEEG, not the best \[35\] or seizures (clinical or electrical) thus meeting ONE of the following: 1. Normal background with some (\> 5 min) electrical seizure activity 2. Moderately abnormal activity (upper margin of trace \>10μV and lower margin \<5μV) 3. Suppressed activity (upper margin of trace \<10μV and lower margin of trace \<5μV) 4. Definite seizure activity Additional inclusion criteria for xenon: Before being considered for additional inhaled xenon therapy via the breathing gas mixture, the infant would need to meet further additional entry criteria (all must be met): 1. Intubated, ventilated, sedated, being cooled 2. ≤ 5 hours old 3. Any seizures under control 4. Weight \> 2nd centile for gestational age 5. Stable cardiovascular parameters; Mean arterial pressure \>40mmHg. 6. Oxygen requirement via mechanical ventilator ≤ 40%. 7. Positive End Expiratory Pressure (PEEP) requirement ≤ 8cm H2O 8. Arterial (preferable)/capillary/venous pCO2 within acceptable range (\<7kPa) 9. Postnatal age ≤ 5 hours 10. Absence of major congenital abnormalities, imperforate anus and in particular any bowel obstruction, congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis. Congenital syndromes affecting the brain should be excluded when diagnosed.
Exclusion criteria
for cooling in the CoolXenon3 study: 1. Infants expected to be greater than 3 hours of age at the time of starting cooling treatment. 2. Futility. Where prognosis is considered to be hopeless e.g. no cardiac output for 20 minutes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death and moderate or severe disability - Bayley III neurodevelopmental outcome score | 18 months of age | Cognition, language and motor scores, hearing and vision |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain MRI | Before hospital discharge, within 2 weeks of birth | Magnetic Resonance Imaging findings at less than 2 weeks of age |
| Amplitude Integrated Electroencephalogram (aEEG) grading | Before hospital discharge, usually within 1 week of birth | Number of hours after birth when aEEG voltage has reached a normal or discontinuous normal pattern |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of normal infants | 18-24 months | Bayley III composite score ≥ 85 and no neurosensory disability as described above |
Countries
United Kingdom
Outcome results
None listed