Plain English Summary
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
Trial website
Additional identifiers
EudraCT number
2009-014344-11
ClinicalTrials.gov number
NCT00934700
Protocol/serial number
G0701714; prot-001-2009
Study information
Scientific title
Neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia: a randomised controlled trial
Acronym
TOBYxe
Study hypothesis
Following perinatal asphyxia treatment with a combination of hypothermia and inhaled xenon preserves cerebral metabolism and structure.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient 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
Condition
Perinatal asphyxia with hypoxic-ischaemic encephalopathy
Intervention
Infants 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 type
Drug
Phase
Not Applicable
Drug names
Xenon
Primary outcome measure
Reduction in Lac/Naa ratio on magnetic resonance spectroscopy or preserved fractional anisotropy diffusion weighted magnetic resonance imaging.
Secondary outcome measures
Measured 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 trial start date
01/02/2012
Overall trial end date
30/09/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 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
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
92
Participant exclusion criteria
1. 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
Recruitment start date
01/02/2012
Recruitment end date
30/09/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Department of Paediatrics
London
W12 5HS
United Kingdom
Sponsor information
Organisation
Imperial College London (UK)
Sponsor details
c/o Gary Roper
Hammersmith Campus
DuCane Road
London
W12 5HS
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK) (ref: G0701714)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/26708675