Clinical trial NCT00934700: Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia
Official title: Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypoxic Ischaemic Encephalopathy
Keywords: perinatal asphyxia
encephalopathy
neuroprotection
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University College London Hospitals
name: Guy's and St Thomas' NHS Foundation Trust
First posted: 2009-07-08
Enrollment: 92
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy
timeFrame: 10 days
measure: Cerebral Fractional Anisotropy Measured by Diffusion Weighted Magnetic Resonance Imaging
timeFrame: 10 days
Secondary outcomes:
measure: Amiel Tison Evaluation at Hospital Discharge
timeFrame: At discharge from hospital
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Academic Healthcare Trust
Study officials:
affiliation: Imperial College London
name: Denis Azzopardi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. Lancet Neurol. 2016 Feb;15(2):145-153. doi: 10.1016/S1474-4422(15)00347-6. Epub 2015 Dec 19.
citation: Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.