Clinical Trial: TOBY (TOtal Body hYpothermia): a Study of Treatment for Perinatal Asphyxia
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Whole Body Hypothermia for the Treatment of Perinatal Asphyxial Encephalopathy
Brief Summary:
Hypothesis: Prolonged whole body cooling in term infants with perinatal asphyxial encephalopathy reduces death and severe neurodevelopmental disability.
This study aims to determine whether whole body cooling to 33-34°C is a safe treatment that improves survival, without severe neurological or neurodevelopmental impairments at 18 months, of term infants suffering perinatal asphyxial encephalopathy.
Detailed Summary:
This is a multicentre prospective randomised controlled trial to determine whether a reduction of body temperature by 3-4°C following perinatal asphyxia improves survival without neurodevelopmental disability.
Full term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 ± 0.2°C or to whole body cooling with the rectal temperature kept at 33.5 ± 0.5°C for 72 hours followed by slow rewarming.
The outcome will be assessed at 18 months of age by survival and neurological and neurodevelopmental testing.
Eligibility criteria:
Term infants less than 6 hours after birth with moderate or severe perinatal asphyxia (a combination of clinical and EEG criteria).
Exclusion criteria:
Infants expected to be 6 hours of age at the time of randomisation or infants with major congenital abnormalities.
Intervention:
Intensive care with whole body cooling versus intensive care without whole body cooling (babies are cooled to 33.5°C for 72 hours)
Main Outcomes:
Death and severe neurodevelopmental impairment at 18 months of age
Secondary Outcomes:
Cerebral thrombosis or haemorrhage, persistent hypotension, pulmonary hypertension, abnormal coagulation, arrhythmia and sepsis in the neonatal period. Neurological impairments at 18 months
Severe neurodevelopmental disability was defined as a score of less than 70 on the Mental Developmental Index of the Bayley Scales of Infant Development II (BSID-II) (on which the standardization mean [± standard deviation (SD)] is 100±15 and higher scores indicate better performance), a score of 3 to 5 on the Gross Motor Function Classification System (GMFCS) (on which scores can range from 1 to 5, with higher scores indicating greater impairment), or bilateral cortical visual impairment with no useful vision.
Original Primary Outcome: Combined incidence of mortality and severe neurodevelopmental disability in survivors at 18 months of age.
Current Secondary Outcome:
- Intracranial Haemorrhage [ Time Frame: Duration of hospital stay, on average 22 days ]Intracranial hemorrhage was identified on magnetic resonance imaging (MRI).
- Persistent Hypotension [ Time Frame: Duration of hospital stay, on average 22 days ]Hypotension was defined as a mean blood pressure of 40 mm Hg or less and was persistent if causes of hypotension had been sought and appropriate treatment provided, without success.
- Pulmonary Haemorrhage [ Time Frame: Duration of hospital stay, on average 22 days ]
- Pulmonary Hypertension [ Time Frame: Duration of hospital stay, on average 22 days ]
- Prolonged Blood Coagulation Time [ Time Frame: Duration of hospital stay, on average 22 days ]
- Culture Proven Sepsis [ Time Frame: Duration of hospital stay, on average 22 days ]
- Necrotising Enterocolitis [ Time Frame: Duration of hospital stay, on average 22 days ]
- Cardiac Arrhythmia [ Time Frame: Duration of hospital stay, on average 22 days ]Arrhythmia identified on electrocardiogram (ECG), e.g. sinus bradycardia <80 beats per minute, ventricular arrhythmia.
- Thrombocytopenia [ Time Frame: Duration of hospital stay, on average 22 days ]
- Major Venous Thrombosis [ Time Frame: Duration of hospital stay, on average 22 days ]
- Renal Failure Treated With Dialysis [ Time Frame: Duration of hospital stay, on average 22 days ]
- Pneumonia [ Time Frame: Before discharge from hospital ]
- Pulmonary Airleak [ Time Frame: Duration of hospital stay, on average 22 days ]
- Duration of Hospitalisation [ Time Frame: Duration of hospital stay, on average 22 days ]Total duration of hospital care
- Mortality [ Time Frame: 18 months ]
- Severe Neurodevelopmental Disability [ Time Frame: 18 months ]
- Multiple Handicap [ Time Frame: 18 months ]defined as the presence of any two of the following in an infant; neuromotor disability (Level 3-5 on Gross Motor Function classification), mental delay (Bayley Mental Developmental Index (MDI) score < 70), epilepsy, cortical visual impairment, sensorineural hearing loss
- Bayley Psychomotor Developmental Index Score (PDI) [ Time Frame: 18 months ]Bayley Psychomotor Developmental Index score (PDI) <70
- Sensorineural Hearing Loss [ Time Frame: 18 months ]Normal or near normal hearing, no sensorineural hearing loss
- Epilepsy (Defined as Recurrent Seizures Beyond the Neonatal Period, Requiring Anticonvulsant Therapy at the Time of Assessment) [ Time Frame: 18 months ]
- Microcephaly [ Time Frame: 18 months ]Head circumference at follow-up >2 standard deviations below the mean
Original Secondary Outcome:
- 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; neuromotor disability (Level 3-5 on GMF classification), mental delay (Bayley MDI score < 70), epilepsy, cortical visual impairment, sensorineural hearing loss)
- 4. Bayley PDI score
- 5. Sensorineural hearing loss: 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).
Information By: Imperial College London
Dates:
Date Received: September 5, 2005
Date Started: December 2002
Date Completion:
Last Updated: April 6, 2016
Last Verified: November 2013