TOBY (TOtal Body hYpothermia): a Study of Treatment for Perinatal Asphyxia

Not Applicable

Completed

Conditions: Seizures
Asphyxia Neonatorum
Hypoxia
Encephalopathy

Interventions: Procedure: Whole body mild induced hypothermia

Registration Number: NCT00147030

Lead Sponsor: Imperial College London

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 Description: 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

Number of patients required: 236.

On 30th November 2006, when recruitment closed, 325 babies had been recruited.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 325

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cooled	Whole body mild induced hypothermia	Whole body mild induced hypothermia for 72 hours, starting by 6 hours of age, in addition to standard intensive care. After 72 hours of cooling, rewarming by a maximum of 0.5 degree C / hour to normothermia.

Primary Outcome Measures

Name	Time	Method
Combined Incidence of Mortality and Severe Neurodevelopmental Disability in Survivors	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.

Secondary Outcome Measures

Name	Time	Method
Culture Proven Sepsis	Duration of hospital stay, on average 22 days
Major Venous Thrombosis	Duration of hospital stay, on average 22 days
Sensorineural Hearing Loss	18 months	Normal or near normal hearing, no sensorineural hearing loss
Intracranial Haemorrhage	Duration of hospital stay, on average 22 days	Intracranial hemorrhage was identified on magnetic resonance imaging (MRI).
Persistent Hypotension	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 Hypertension	Duration of hospital stay, on average 22 days
Prolonged Blood Coagulation Time	Duration of hospital stay, on average 22 days
Necrotising Enterocolitis	Duration of hospital stay, on average 22 days
Cardiac Arrhythmia	Duration of hospital stay, on average 22 days	Arrhythmia identified on electrocardiogram (ECG), e.g. sinus bradycardia \<80 beats per minute, ventricular arrhythmia.
Thrombocytopenia	Duration of hospital stay, on average 22 days
Pulmonary Haemorrhage	Duration of hospital stay, on average 22 days
Epilepsy (Defined as Recurrent Seizures Beyond the Neonatal Period, Requiring Anticonvulsant Therapy at the Time of Assessment)	18 months
Renal Failure Treated With Dialysis	Duration of hospital stay, on average 22 days
Severe Neurodevelopmental Disability	18 months
Microcephaly	18 months	Head circumference at follow-up \>2 standard deviations below the mean
Pneumonia	Before discharge from hospital
Pulmonary Airleak	Duration of hospital stay, on average 22 days
Duration of Hospitalisation	Duration of hospital stay, on average 22 days	Total duration of hospital care
Mortality	18 months
Multiple Handicap	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)	18 months	Bayley Psychomotor Developmental Index score (PDI) \<70