TOBY: a Study of Treatment for Perinatal Asphyxia
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Purpose
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: Whole body mild induced hypothermia |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Whole Body Hypothermia for the Treatment of Perinatal Asphyxial Encephalopathy |
- Combined incidence of mortality and severe neurodevelopmental disability in survivors [ Time Frame: 18 months ]
- Intracranial haemorrhage [ Time Frame: Before discharge from hospital ]
- Persistent hypotension [ Time Frame: Before discharge from hospital ]
- Pulmonary haemorrhage [ Time Frame: Before discharge from hospital ]
- Pulmonary hypertension [ Time Frame: Before discharge from hospital ]
- Prolonged blood coagulation time [ Time Frame: Before discharge from hospital ]
- Culture proven sepsis [ Time Frame: Before discharge from hospital ]
- Necrotising enterocolitis [ Time Frame: Before discharge from hospital ]
- Cardiac arrhythmia [ Time Frame: Before discharge from hospital ]
- Thrombocytopenia [ Time Frame: Before discharge from hospital ]
- Major venous thrombosis [ Time Frame: Before discharge from hospital ]
- Renal failure treated with dialysis [ Time Frame: Before discharge from hospital ]
- Pneumonia [ Time Frame: Before discharge from hospital ]
- Pulmonary airleak [ Time Frame: Before discharge from hospital ]
- Duration of hospitalisation [ Time Frame: Before discharge from hospital ]
- Mortality [ Time Frame: 18 months ]
- Severe neurodevelopmental disability [ Time Frame: 18 months ]
- 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) [ Time Frame: 18 months ]
- Bayley PDI score [ Time Frame: 18 months ]
- Sensorineural hearing loss: 40 dB [ Time Frame: 18 months ]
- Epilepsy (defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment) [ Time Frame: 18 months ]
- Microcephaly (head circumference more than 2 standard deviations below the mean). [ Time Frame: 18 months ]
| Enrollment: | 325 |
| Study Start Date: | December 2002 |
| Study Completion Date: | August 2008 |
| Primary Completion Date: | November 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: 1 |
Procedure: Whole body mild induced hypothermia
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
|
| No Intervention: 2 |
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.
Eligibility| Ages Eligible for Study: | up to 6 Hours |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United Kingdom | |
| Hammersmith Hospital | |
| London, United Kingdom, W12 0NN | |
| Principal Investigator: | Denis Azzopardi, MD; FRCPCH | Imperial College London |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00147030 History of Changes |
| Other Study ID Numbers: | ISRCTN89547571 |
| Study First Received: | September 5, 2005 |
| Last Updated: | April 17, 2009 |
| Health Authority: | United Kingdom: Research Ethics Committee |
Keywords provided by Imperial College London:
|
Hypoxia Ischaemia Encephalopathy Neonatal |
Hypothermia Perinatal Cooling Whole/Total Body |
Additional relevant MeSH terms:
|
Asphyxia Neonatorum Asphyxia Hypothermia Seizures Brain Damage, Chronic Delirium Encephalitis Hepatic Encephalopathy Neurotoxicity Syndromes Anoxia Death Pathologic Processes Wounds and Injuries Infant, Newborn, Diseases Body Temperature Changes |
Signs and Symptoms Epilepsy Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurologic Manifestations Confusion Neurobehavioral Manifestations Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Central Nervous System Viral Diseases Virus Diseases Central Nervous System Infections Liver Failure Hepatic Insufficiency |
ClinicalTrials.gov processed this record on May 21, 2013