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

Imperial College London325 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

325

Conditions

Asphyxia Neonatorum Hypoxia Encephalopathy Seizures

Interventions

Whole body mild induced hypothermiaPROCEDURE

Target rectal temperature 33-34°C for 72 hours, commencing by 6 hours of age; followed by re-warming at 0.5°C to normothermia

Eligibility

Sex: ALLMin age: 1 HourMax age: 6 Hours

Medical Language ↔ Plain English

Inclusion criteria The infant will be assessed sequentially by criteria A, B and C listed below: A. Infants =\>36 completed weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) with at least one of the following: * Apgar score of =\<5 at 10 minutes after birth * Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth * Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary pH \<7.00) * Base Deficit =\>16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel: B. Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following: * hypotonia * abnormal reflexes including oculomotor or pupillary abnormalities * absent or weak suck * clinical seizures Infants that meet criteria A \& B will be assessed by amplitude-integrated electroencephalogram (aEEG) (read by trained 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: * normal background with some seizure activity * moderately abnormal activity * suppressed activity * continuous seizure activity Exclusion criteria * Infants expected to be \> 6 hours of age at the time of randomisation * Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis

Locations (1)

Hammersmith Hospital

London, United Kingdom

Outcomes

Primary Outcomes

Combined Incidence of Mortality and Severe Neurodevelopmental Disability in Survivors

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.

Time frame: 18 months