Neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia

ISRCTN ISRCTN08886155
DOI https://doi.org/10.1186/ISRCTN08886155
EudraCT/CTIS number 2009-014344-11
ClinicalTrials.gov number NCT00934700
Secondary identifying numbers G0701714; prot-001-2009
Submission date
03/07/2009
Registration date
30/07/2009
Last edited
17/03/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
This is a study of infants suffering from perinatal asphyxia (lack of oxygen during birth) comparing standard care (cooling of the baby) with standard care and additional xenon gas inhaled through a ventilator. The study examines the feasibility and safety of inhaled xenon gas to see whether treatment with the combination of cooling and xenon gas may reduce brain injury, assessed by a MRI scan of the brain at around 8 days of age.

Who can participate?
Infants from 36 to 43 weeks gestation, following perinatal asphyxia

What does the study involve?
Infants are randomly allocated to one of two groups. One group is treated with intensive care and treatment with hypothermia (cooling) for 72 hours combined with inhaled xenon gas for 24 hours. The other group is treated with intensive care with hypothermia for 72 hours. MRI scans are performed once at between 4 - 10 days of age.

What are the possible benefits and risks of participating?
If the study is successful larger studies can be carried out to confirm whether treatment with xenon improves neurological (brain) function after birth asphyxia.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
February 2012 to September 2014

Who is funding the study?
Medical Research Council (MRC) (UK)

Who is the main contact?
Dr Denis Azzopardi

Study website

Contact information

Dr Denis Azzopardi
Scientific

Department of Paediatrics
Hammersmith House
DuCane Road
London
W12 5HS
United Kingdom

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Patient information can be found at: https://www.npeu.ox.ac.uk/downloads/files/toby-xe/consent/TOBY-Xe-PIL-V7-Fax-Version.pdf
Scientific titleNeuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia: a randomised controlled trial
Study acronymTOBYxe
Study objectivesFollowing perinatal asphyxia treatment with a combination of hypothermia and inhaled xenon preserves cerebral metabolism and structure.
Ethics approval(s)Not provided at time of registration
Health condition(s) or problem(s) studiedPerinatal asphyxia with hypoxic-ischaemic encephalopathy
InterventionInfants will be allocated to one of two groups: intensive care and treatment with hypothermia for 72 hours combined with inhaled 30% xenon gas for 24 hours or intensive care with hypothermia for 72 hours. Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) will be performed once between 4 - 10 days of age.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Xenon
Primary outcome measureReduction in Lac/Naa ratio on magnetic resonance spectroscopy or preserved fractional anisotropy diffusion weighted magnetic resonance imaging.
Secondary outcome measuresMeasured prior to hospital discharge:
1. Intracranial haemorrhage
2. Persistent hypotension
3. Pulmonary haemorrhage
4. Pulmonary hypertension
5. Prolonged blood coagulation time
6. Culture proven sepsis
7. Necrotising enterocolitis
8. Cardiac arrhythmia
9. Thrombocytopenia
10. Major venous thrombosis
11. Renal failure treated with dialysis
12. Pneumonia
13. Pulmonary airleak
14. Duration of hospitalisation
Overall study start date01/02/2012
Completion date30/09/2014

Eligibility

Participant type(s)Patient
Age groupNeonate
SexBoth
Target number of participants92
Key inclusion criteria1. Infants 36 to 43 weeks gestation (either sex) with at least one of the following:
1.1. Apgar score of less than 5 at 10 minutes after birth
1.2. Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
1.3. Acidosis defined as pH less than 7.00 and/or base deficit x 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)
2. 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 hypoxic-ischaemic encephalopathy (HIE) will be assessed by Thompson encephalopathy score, and modified Sarnat score
3. At least 30 minutes duration of amplitude integrated EEG (aEEG) recording that shows moderately abnormal or suppressed background aEEG activity or seizures
Key exclusion criteria1. If treatment with hypothermia is delayed beyond 6 hours, or infants are expected to be greater than 12 hours of age at the time of randomisation
2. Infants with ventilatory oxygen requirement greater than 70%
3. Attending clinician considers infant not suitable to participate because of other serious congenital abnormalities, or the infant's condition appears terminal
Date of first enrolment01/02/2012
Date of final enrolment30/09/2014

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Department of Paediatrics
London
W12 5HS
United Kingdom

Sponsor information

Imperial College London (UK)
University/education

c/o Gary Roper
Hammersmith Campus
DuCane Road
London
W12 5HS
England
United Kingdom

Website http://www3.imperial.ac.uk/
ROR logo "ROR" https://ror.org/041kmwe10

Funders

Funder type

Research council

Medical Research Council (MRC) (UK) (ref: G0701714)
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/02/2016 Yes No

Editorial Notes

17/03/2017: Plain English summary added.
29/12/2015: Publication reference added.
31/10/2014: The following changes were made to the trial record:
1. The overall trial start date was changed from 15/09/2009 to 01/02/2012
2. The overall trial end date was changed from 14/09/2012 to 30/09/2014
3. The target number of participants was changed from 130 to 92