This trial is active, not recruiting.

Condition hypoxic ischaemic encephalopathy
Treatments xenon gas, whole body cooling
Phase phase 1/phase 2
Sponsor United Bristol Healthcare NHS Trust
Collaborator University of Bristol
Start date May 2012
End date October 2013
Trial size 32 participants
Trial identifier NCT01545271, 12/SW/0010, 2011-005397-34, CH/2011/3799


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Babies in poor condition at birth and referred to our neonatal unit for standard therapy of cooling to 33.5 degree C body temperature will be randomised to receive xenon gas at 50% concentration for 18 hours
xenon gas
Inhalation via endotracheal tube of 50% xenon for 18 hours
whole body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment)
(Active Comparator)
Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)
whole body cooling
Cooling of baby to reduce rectal temperature to 33.5 degree Centigrade(standard treatment)

Primary Outcomes

Amplitude Integrated Electroencephalogram (aEEG) grading
time frame:
Brain MRI
time frame: less than 2 weeks of age

Eligibility Criteria

Male or female participants of any age.

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 ≤ 6cm H2O 8. Arterial pCO2 within acceptable range (<7kPa) 9. 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 CoolXenon2 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.

Additional Information

Official title Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot Study
Principal investigator Marianne Thoresen, Professor
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by United Bristol Healthcare NHS Trust.