Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia

Hypoxic Ischaemic Encephalopathy Clinical Trial

— TOBYXe  

Official title:

Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00934700
• Other study ID #: prot-002-2009
• Status: Completed
• Phase: N/A
• Start date: February 2012
• Est. completion date: September 2014

Study information

• Verified date: April 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised controlled trial in newborn infants with perinatal asphyxial encephalopathy assessing whether a combination of hypothermia and inhaled xenon preserve cerebral metabolism and structure.

Description:

The study hypothesis is that: Following perinatal asphyxia treatment with a combination of hypothermia and inhaled xenon preserves cerebral metabolism and structure. Following informed parental consent, infants that continue to require endotracheal tube ventilation following resuscitation will be randomised to treatment with hypothermia only or hypothermia and xenon. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants allocated to hypothermia and xenon will also receive 30% xenon (balanced with oxygen and air) for 24 hours through a purpose designed delivery system. Structured neurological examination will be done daily during the 1st week after birth and at discharge. MRS and MRI will be performed once between 4-10 days of age. MRS/MRI data analysis will be by investigators blinded to the allocated intervention.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Hours

Eligibility

Inclusion Criteria:

Infants will be eligible for enrolment into the trial if each of the following criteria is fulfilled:

• Infants 36 to 43 weeks gestation with at least one of the following:

• Apgar score of <5 at 10 minutes after birth;

• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth;

• Acidosis defined as pH <7.00 and/or base deficit >15 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood).

• Moderate to severe encephalopathy consisting of altered state of consciousness (reduced or absent response to stimulation) and hypotonia, and abnormal primitive reflexes (weak or absent suck or Moro response). Clinical severity of HIE will be assessed by Thompson encephalopathy score, and modified Sarnat score.

• At least 30 minutes duration of amplitude integrated EEG (aEEG) recording that shows moderately abnormal or suppressed background aEEG activity or seizures

Exclusion Criteria:

• If treatment with hypothermia is delayed beyond 6 hours, or infants are expected to be >12 hours of age at the time of randomisation; Infants with ventilatory oxygen requirement > 70%; Attending clinician considers infant not suitable to participate because of other serious congenital abnormalities, or the infant's condition appears terminal.

Related Conditions & MeSH terms

• Asphyxia
• Brain Diseases
• Brain Ischemia
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic Ischaemic Encephalopathy

Intervention

Other:
• Xenon gas
30% Xenon gas inhaled for 24 hours

Locations

Country	Name	City	State
United Kingdom	Imperial College Academic Healthcare Trust	London

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	Guy's and St Thomas' NHS Foundation Trust, University College London Hospitals

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Azzopardi D, Robertson NJ, Bainbridge A, Cady E, Charles-Edwards G, Deierl A, Fagiolo G, Franks NP, Griffiths J, Hajnal J, Juszczak E, Kapetanakis B, Linsell L, Maze M, Omar O, Strohm B, Tusor N, Edwards AD. Moderate hypothermia within 6 h of birth plus i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy	Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents	10 days
Primary	Cerebral Fractional Anisotropy Measured by Diffusion Weighted Magnetic Resonance Imaging	Fractional anisotropy (FA) is a measure of tissue integrity in white matter tracts measured by diffusion tensor MRI, and it has been used in work in animals to assess potential neuroprotectants and can be used to predict subsequent neurological outcomes after birth asphyxia, including in infants treated with moderate hypothermia.; It is a scalar value between 0-1 that describe anisotropy of a diffusion process. A value of zero means that diffusion is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions" or similar.; Fractional anisotropy data were extracted froma mask of the posterior limb of the internal capsule via tract-based spatial statistics. *Coefficient of variation=v(exp(var)-1), where var is the variance on the log scale	10 days
Secondary	Amiel Tison Evaluation at Hospital Discharge	Amiel Tison neurological assessment at discharge from hospital. Amiel Tison evaluation was developed to detect transient and permanent abnormalities in an infant's neuromotor development. Its main focus is to examine active and passive muscle tone.	At discharge from hospital