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| [ Print-friendly version ] |
| Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy |
| ISRCTN | ISRCTN89547571 |
| ClinicalTrials.gov identifier | NCT00147030 |
| Public title | Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy |
| Scientific title | |
| Acronym | TOBY (TOtal Body hYpothermia) |
| Serial number at source | G0100126 |
| Study hypothesis |
1. To determine whether whole body cooling for 72 hours in term infants with perinatal asphyxial encephalopathy improves survival without neurological or neurodevelopmental disability at 18 months
2. To confirm the safety of prolonged whole body cooling in full term infants with perinatal asphyxial encephalopathy |
| Ethics approval | Added as of 12/10/2007: Approved by London Multi-centre Research Ethics Committee (MREC) on 8th January 2002 (ref: MREC 00/02/73) |
| Study design | Randomised controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Obstetrics and gynaecology |
| Participants - inclusion criteria |
Infants will be assessed sequentially by criteria A, B and C listed below:
A. Infants greater than or equal to 36 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) with ONE of the following: 1. Apgar score of less than five at ten 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 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 criteria A then assess for neurological abnormality (by trained study personnel): B. Moderate to severe encephalopathy consisting of altered state of consciousness (lethargy, stupor or coma) and at least one or more of hypotonia, abnormal reflexes including oculomotor or pupillary abnormalities, an absent or weak suck or clinical seizures, as recorded by study personnel. If the infant meets criteria A & B then assess by amplitude-integrated electroencephalography (aEEG) (read by trained study personnel): C. At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following: 1. Normal background with some seizure activity 2. Moderately abnormal activity 3. Suppressed activity 4. Continuous seizure activity |
| Participants - exclusion criteria |
1. Infants expected to be greater than 5.5 hours of age at the time of randomization
2. Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis |
| Anticipated start date | 01/09/2002 |
| Anticipated end date | 01/09/2008 |
| Status of trial | Completed |
| Patient information material | Patient information can be found at: http://www.npeu.ox.ac.uk/TOBY/toby_downloads/toby_pil1.pdf |
| Target number of participants | The original target was 236, which was achieved earlier than expected. Ethics approval for a revised target of 400 was obtained to continue recruitment. 325 babies actually recruited. |
| Interventions |
Full term infants will be randomized within six hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2 degrees celsius or to whole body cooling with the rectal temperature kept at 33.5 +/- 0.5 degrees celsius for 72 hours followed by slow rewarming.
Relevant physiological parameters will be monitored and outcome assessed at 18 months of age by survival and neurological and neurodevelopmental testing. Recruitment closed at the end of the planned recruitment phase on 30/11/2006. |
| Primary outcome measure(s) | The primary outcome for this trial is a combined endpoint: death in the first 18 months of life OR Severe neurodevelopmental disability. |
| Secondary outcome measure(s) |
Secondary outcome measures added as of 16/10/2007:
Short term (before discharge from hospital): 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 Long term (at 18 months): 1. Mortality 2. Severe neurodevelopmental disability 3. Multiple handicap, defined as the presence of any two of the following in an infant: 3.1. Neuromotor disability (Level 3-5 on General Motor Function (GMF) Assessment Scale classification), mental delay (the Bayley Scales of Infant Development - Mental Development Indices (MDI) score less than 70), epilepsy, cortical visual impairment, sensorineural hearing loss 4. The Bayley Scales of Infant Development - Psychomotor Development Indices (PDI) score 5. Sensorineural hearing loss: greater than or equal to 40 dB 6. Epilepsy (defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment) 7. Microcephaly (head circumference more than 2 standard deviations below the mean) |
| Sources of funding | Medical Research Council (UK) |
| Trial website | http://www.npeu.ox.ac.uk/TOBY/ |
| Publications | |
| Contact name | Dr Denis Azzopardi |
| Address |
Department of Paediatrics
ICSTM at Hammersmith Du Cane Road |
| City/town | London |
| Zip/Postcode | W12 0NN |
| Country | United Kingdom |
| Sponsor | Imperial College London (UK) |
| Address |
Research Services, Medicine
Research Services Division Faculty Building South Kensington Campus South Kensington |
| City/town | London |
| Zip/Postcode | SW7 2AZ |
| Country | United Kingdom |
| Sponsor website: | http://www.imperial.ac.uk/ |
| Date applied | 21/09/2000 |
| Last edited | 16/10/2007 |
| Date ISRCTN assigned | 21/09/2000 |
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