Randomised pilot study of cooling therapy (standard treatment) versus inhaled xenon gas in combination with cooling, in babies at high risk of brain injury following poor condition at birth.

Phase 1

• Conditions: Neonatal hypoxia-ischaemia (HI). There is no exact MedDRA term for this. The closest MedDRA terms matching this are neonatal asphyxia and neonatal hypoxia.; MedDRA version: 14.1 Level: PT Classification code 10050081 Term: Neonatal hypoxia System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1 Level: HLT Classification code 10028946 Term: Neonatal hypoxia and asphyxia System Organ Class: 10036585 - Pregnancy, puerperium and perinatal conditions; MedDRA version: 14.1 Level: PT Classification code 10028923 Term: Neonatal asphyxia System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

• Registration Number: EUCTR2011-005397-34-GB
• Lead Sponsor: niversity Hospital Bristol NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-02-03
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

Inclusion Criteria
Patients meeting the following criteria will be considered eligible for the study:

Infants will be eligible for inclusion in this study if the St Michael???s hospital standard inclusion criteria for cooling are met and additional inclusion criteria for xenon administration are met.

St Michael???s hospital standard inclusion criteria for cooling
Standard Hypothermia Treatment Criteria for 72 hrs of cooling ??? all of criteria A, B, and C.
A Infants > 36.0 weeks gestation (clinical assessment) with at least ONE of the following:
1 Apgar score of <5 at ten (10) minutes after birth
2 Continued need for resuscitation, including endotracheal or mask ventilation, at ten minutes after birth
3Acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less than pH 7.00
4Base deficit greater than or equal to 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):

BModerate or Severe encephalopathy as evidenced by any of the following --
1Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive and at least ONE or more of the following:
2Hypotonia
3Abnormal reflexes including oculomotor or pupillary abnormalities
4Absent or weak suck
5Clinical seizures, as recorded by trained personnel
And
CAt 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 section of the aEEG, not the best (al Naqeeb, et al, 1999) or seizures (clinical or electrical) thus meeting ONE of the following:
1Normal background with some electrical seizure activity
2Moderately abnormal activity (upper margin of trace >10µV and lower margin <5µV)
3Suppressed activity (upper margin of trace <10µV and lower margin of trace <5µV)
4Definite seizure activity
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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 the accepted range (4.0-6.5 kPa)
9)Postnatal age <5 hours
10)Absence of major congenital abnormalities, imperforate anus and in particular any bowel obstruction, congenital abnormalities

Exclusion Criteria

Exclusion Criteria

Exclusion criteria for cooling
1.Infants expected to be greater than 5 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 exclusion criteria for xenon
Failure to meet any of the additional inclusion criteria for xenon listed in section 5.1.
Patients meeting the following criteria are NOT eligible for the study:
Presence of any 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. (Neonates with congenital syndromes affecting the brain should be excluded when diagnosed).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified