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.

Condition	Intervention
Asphyxia Neonatorum Hypoxia Encephalopathy Seizures	Procedure: Induced mild whole body hypothermia

Further Study Details: 

Primary Outcomes: Combined incidence of mortality and severe neurodevelopmental disability in survivors at 18 months of age.
Secondary Outcomes: 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).
Expected Total Enrollment:  236

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

Ages Eligible for Study:  up to  6 Hours,  Genders Eligible for Study:  Both

Criteria

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 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 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00147030

Denis Azzopardi, MD FRCPCH      +44 (0) 208 383 3326    d.azzopardi@imperial.ac.uk

United Kingdom
      Hammersmith Hospital, London,  W12 0NN,  United Kingdom; Recruiting

Study chairs or principal investigators

Denis Azzopardi, MD; FRCPCH,  Principal Investigator,  Imperial College London   

Study ID Numbers:  ISRCTN 89547571
Last Updated:  September 6, 2005
Record first received:  September 5, 2005
ClinicalTrials.gov Identifier:  NCT00147030
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
ClinicalTrials.gov processed this record on 2005-09-13