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
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
Contact information
Scientific
Department of Paediatrics
Hammersmith House
DuCane Road
London
W12 5HS
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 title | Neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia: a randomised controlled trial |
| Study acronym | TOBYxe |
| Study objectives | Following 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) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/02/2012 |
| Completion date | 30/09/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 92 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/02/2012 |
| Date of final enrolment | 30/09/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
W12 5HS
United Kingdom
Sponsor information
University/education
c/o Gary Roper
Hammersmith Campus
DuCane Road
London
W12 5HS
England
United Kingdom
| Website | http://www3.imperial.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Research council
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 share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not 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
