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| [ ...Back to search results ] | [ Print-friendly version ] |
| The CoolXenon Study |
| ISRCTN | ISRCTN75602528 |
| ClinicalTrials.gov identifier | |
| Public title | The CoolXenon Study |
| Scientific title | A feasibility study of adding xenon to cooling therapy in babies at high risk of brain injury following poor condition at birth |
| Acronym | CoolXenon |
| Serial number at source | Version 1.21 (as of 05/01/2011) |
| Study hypothesis |
Our experimental work has shown that by adding the inert gas xenon (50%) while undergoing hypothermia treatment the % good outcome doubles (from 35% to 70%) in both small and large survival models. This is the first clinical feasibility study combining xenon inhalation with the established neuroprotective hypothermia treatment in newborn term after moderate and severe perinatal asphyxia.
Further reading: Dingley J, Tooley J. Porter H, Thoresen M. Xenon provides short term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke 2006; 37(2): 501-6. http://www.ncbi.nlm.nih.gov/pubmed/16373643 Dingley J, Hobbs C, Ferguson J, Thoresen M. Xenon/hypothermia neuroprotection regimes in spontaneously breathing neonatal rats after hypoxic-ischemic insult: respiratory and sedative effects. Anaesthesia and Analgesia 2008; 106: 916-923. http://www.ncbi.nlm.nih.gov/pubmed/18292440 Hobbs C, Thoresen M, Tucker AM, Aquilina K, Chakkarapani E, Dingley J. Xenon and hypothermia combine additively offering long term functional and histopathological neuroprotection after neonatal hypoxia-ischemia. Stroke 2008; 39(4): 1307-13. http://www.ncbi.nlm.nih.gov/pubmed/18309163 Chakkarapani E, Thoresen M, Hobbs C, Aquilina K, Liu X, Dingley J. A closed-circuit neonatal xenon delivery system: technical neuroprotection feasibility study in newborn pigs. Anaesthesia and Analgesia 2009; 109(2): 451-60. http://www.ncbi.nlm.nih.gov/pubmed/19608817 Thoresen M, Hobbs C, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed Xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. Journal of Cerebral Blood Flow and Metabolism 2009; 29(4): 707-14. http://www.ncbi.nlm.nih.gov/pubmed/19142190 Thoresen M. Patient selection and prognostication with hypothermia treatment. Seminars in Fetal and Neonatal Medicine 2010; 15(5): 247-52 http://www.ncbi.nlm.nih.gov/pubmed/20580626 As of 01/03/2011 the target number of participants has been increased from 12 to 14 |
| Lay summary | |
| Ethics approval | North Somerset and South Bristol Research Ethics Committee approved on the 16th September 2009 (ref: 09/H0106/64) |
| Study design | Interventional non-randomised single centre feasibility study |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Topic: Neurological; Subtopic: Neurological (all Subtopics); Disease: Nervous system disorders |
| Participants - inclusion criteria |
Infants will be eligible for xenon if the St Michael's standard inclusion criteria for cooling are met. Standard Hypothermia Treatment Criteria for 72 hours of cooling - all of criteria A, B, and C:
A: Infants greater than 36.0 weeks gestation (clinical assessment) with at least one of the following: 1. Apgar score of less than 5 at ten (10) minutes after birth 2. Continued need for resuscitation, including endotracheal or mask ventilation, at ten minutes after birth 3. Acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less than pH 7.00 4. Base deficit greater than or equal to 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood) If the infant meets criterion A then assess for neurological abnormality using criterion B and C (by trained personnel). B: Moderate or severe encephalopathy as evidenced by: 1. Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive And at least one or more of the following: 2. Hypotonia 3. Abnormal reflexes including oculomotor or pupillary abnormalities 4. Absent or weak suck 5. Clinical seizures, as recorded by trained personnel C: At least 30 minutes duration of amplitude integrated electroencephalography (aEEG) recording that shows abnormal background aEEG activity. The decision to cool is based on the worst section of the aEEG, not the best (al Naqeeb, et al, 1999) or seizures (clinical or electrical) thus meeting ONE of the following: 1. Normal background with some electrical seizure activity 2. Moderately abnormal activity (upper margin of trace greater than 10 µV and lower margin less than 5 µV) 3. Suppressed activity (upper margin of trace less than 10 µV and lower margin of trace less than 5 µV) 4. Definite seizure activity Additional inclusion criteria for xenon: Before being considered for additional inhaled xenon therapy via the breathing gas mixture, the infant would need to meet further additional entry criteria: 1. Intubated, ventilated, sedated, being cooled 2. Any seizures under control 3. Weight greater than 2.3 kg 4. No evidence of infection 5. Stable cardiovascular parameters - mean arterial pressure greater than 45mmHg 6. Oxygen requirement via mechanical ventilator less than 35% 7. Positive end expiratory pressure (PEEP) requirement less than 6 mmHg 8. Arterial pCO2 within the accepted range (4.5 - 6.5 kPa) 9. Postnatal age less than 18 hours, either sex 10. Major congenital abnormalities, imperforate anus and congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis |
| Participants - exclusion criteria |
1. Infants expected to be greater than 12 hours of age at the time of starting cooling treatment
2. Futility; where prognosis is considered to be hopeless, e.g. no cardiac output for 20 minutes 3. Failure to meet the additional inclusion criteria for xenon |
| Anticipated start date | 28/03/2010 |
| Anticipated end date | 01/03/2013 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | Added 01/03/2011: 14 (12 at time of registration) |
| Interventions |
Adding xenon to the inspiratory gas of the ventilated infant using a MHRA approved closed loop xenon-delivery system. The xenon, oxygen, carbon dioxide (CO2) and nitrogen gas concentrations are controlled.
Follow up length: 42 months Study entry: registration only Added 01/03/2011: The duration of treatment with Xenon gas has been increased from 12 hours to 18 hours for recruits 12, 13 and 14 |
| Primary outcome measure(s) | Physiological changes, measured within 24 hours after end treatment |
| Secondary outcome measure(s) |
1. Bayley III, measured at 18 or 24 months
2. MRI, measured within 14 days after treatment |
| Sources of funding | Sparks (UK) |
| Trial website | http://www.thoresen.org.uk |
| Publications | |
| Contact name | Prof Marianne Thoresen |
| Address |
School of Clinical Sciences
University of Bristol Neonatology St Michael's Hospital Southwell Street |
| City/town | Bristol |
| Zip/Postcode | BS2 8EG |
| Country | United Kingdom |
| Tel | +44 (0)117 342 5607 |
| Fax | +44 (0)117 342 5751 |
| Marianne.Thoresen@bristol.ac.uk | |
| Sponsor | University Hospitals Bristol NHS Foundation Trust (UK) |
| Address |
Research and Development
Upper Maudlin Street |
| City/town | Bristol |
| Zip/Postcode | BS2 8AE |
| Country | United Kingdom |
| Tel | +44 (0)117 342 0233 |
| Fax | +44 (0)117 342 0239 |
| research@uhbristol.nhs.uk | |
| Sponsor website: | http://www.uhbristol.nhs.uk/ |
| Date applied | 26/11/2010 |
| Last edited | 03/03/2011 |
| Date ISRCTN assigned | 26/11/2010 |
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