Neuroprotective Effects of Hypothermia Combined With Inhaled Xenon Following Perinatal Asphyxia

NCT00934700 | Completed Results DMC

• 1 other identifier: prot-002-2009
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic Ischaemic Encephalopathy

Keywords

perinatal asphyxia; encephalopathy; neuroprotection

Outcome Measures

Primary Outcomes (2)

• Lactate (Lac) / N Acetyl Aspartate (NAA) Ratio on Magnetic Resonance Spectroscopy

  Cerebral Lac/NAA ratio measured by magnetic resonance spectroscopy in patents

  10 days

• 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=√(exp(var)-1), where var is the variance on the log scale

  10 days

Secondary Outcomes (1)

• Amiel Tison Evaluation at Hospital Discharge

  At discharge from hospital

Study Arms (2)

Combination of hypothermia and xenon

EXPERIMENTAL

Combination of hypothermia and inhaled xenon

Other: Xenon gas

Hypothermia and standard intensive care

NO INTERVENTION

Hypothermia and standard intensive care

Interventions

Xenon gas OTHER

30% Xenon gas inhaled for 24 hours

Also known as: LENOXe

Combination of hypothermia and xenon

Eligibility Criteria

• Age: 1 Hour - 12 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imperial College London: lead
• University College London Hospitals: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator

Study Sites (1)

Imperial College Academic Healthcare Trust

London, W12 0HS, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 26708675 RESULT

• 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.

  PMID: 24524452 DERIVED

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Brain Diseases

Interventions

Lasers, Gas

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lasers; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Results Point of Contact

• Title: Research Integrity Officer
• Organization: Imperial College London

jrco@imperial.ac.uk

+44 020 7594 1872

Study Officials

• Denis Azzopardi, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2009
• First Posted: July 8, 2009
• Study Start: February 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 21, 2022
• Results First Posted: April 21, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)