CoolXenon3: Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth

Sponsor

University Hospitals Bristol and Weston NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT02071394

Collaborator

University of Bristol (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypoxic Ischaemic Encephalopathy	Drug: Xenon gas Other: Whole body cooling	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth: A Randomised Pilot Outcomes Study (COOLXENON3 Study)

Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Oct 7, 2019

Anticipated Study Completion Date :

Sep 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 72h cooling + 18h xenon inhalation 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	Drug: Xenon gas Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth. Other Names: LENOXe Other: Whole 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. Other Names: Therapeutic hypothermia
Active Comparator: Standard 72 h whole body cooling therapy Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)	Other: Whole 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. Other Names: Therapeutic hypothermia

Arm

Intervention/Treatment

Experimental: 72h cooling + 18h xenon inhalation

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

Drug: Xenon gas

Inhalation via endotracheal tube of 50% xenon for 18 hours, including during transport for outborn babies, starting within 5 hours after birth.

Other Names:

LENOXe

Other: Whole 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.

Other Names:

Therapeutic hypothermia

Active Comparator: Standard 72 h whole body cooling therapy

Whole body cooling therapy to rectal temperature of 33.5 degree Centigrade (standard therapy)

Other: Whole 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.

Other Names:

Therapeutic hypothermia

Outcome Measures

Primary Outcome Measures

Death and moderate or severe disability - Bayley III neurodevelopmental outcome score [18 months of age]
Cognition, language and motor scores, hearing and vision

Secondary Outcome Measures

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 Outcome Measures

Dubowitz [Seven days]
Developmental assessment
Number of normal infants [18-24 months]
Bayley III composite score ≥ 85 and no neurosensory disability as described above

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Apgar score of ≤5 at ten minutes after birth
Continued need for resuscitation, including tracheal or mask ventilation, at ten minutes after birth
Acidosis, defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less < 7.00
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:

Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive and at least ONE or more of the following:
Hypotonia
Abnormal reflexes including oculomotor or pupillary abnormalities
Absent or weak suck
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:

Normal background with some (> 5 min) electrical seizure activity
Moderately abnormal activity (upper margin of trace >10μV and lower margin <5μV)
Suppressed activity (upper margin of trace <10μV and lower margin of trace <5μV)
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):

Intubated, ventilated, sedated, being cooled
≤ 5 hours old
Any seizures under control
Weight > 2nd centile for gestational age
Stable cardiovascular parameters; Mean arterial pressure >40mmHg.
Oxygen requirement via mechanical ventilator ≤ 40%.
Positive End Expiratory Pressure (PEEP) requirement ≤ 8cm H2O
Arterial (preferable)/capillary/venous pCO2 within acceptable range (<7kPa)
Postnatal age ≤ 5 hours
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:

Infants expected to be greater than 3 hours of age at the time of starting cooling treatment.
Futility. Where prognosis is considered to be hopeless e.g. no cardiac output for 20 minutes.