Clinical Trial: Whole-Body Cooling for Birth Asphyxia in Term Infants
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Randomized Controlled Trial of Hypothermia for Hypoxic-Ischemic Encephalopathy in Term Infants
Brief Summary: This large multicenter trial tested whether cerebral cooling initiated within 6 hours of birth and continued for 72 hours would reduce the risk of death and moderate to severe neurodevelopmental injury at 18-22 months corrected age. Infants at least 36 weeks gestation with an abnormal blood gas within 1 hour of birth, or a history of an acute perinatal event and a 10-min Apgar score <5, or continued need for ventilation were screened. Following a neurological exam, those with moderate to severe encephalopathy were randomized to a 72-hour period of total body cooling (cooling blanket, followed by slow re-warming). The study was conducted in two phases: Phase I (20 infants) were examined for the safety of an esophageal temperature of 34-35 C; Phase II (main trial, 200 infants) were evaluated for the safety and efficacy of an esophageal temperature of 33-34 C. Cardio-respiratory, electroencephalograms (EEGs), renal, metabolic, and hematologic status, and esophageal and abdominal skin temperature were monitored during the 72 hours of intervention. Surviving children were given neurodevelopmental examinations at 18-22 months corrected age and again at school age (6-7 years of age).
Detailed Summary:
Perinatal cerebral hypoxia-ischemia injury is an important cause of death and neurodevelopmental disability. Data from animal models suggest that brain cooling immediately after injury is neuroprotective. Experience with total body cooling during surgery, accidental near drownings, and one Phase I trial of term infants suggest that it is effective and safe in children.
This large multicenter trial tested whether cerebral cooling initiated within 6 hours of birth and continued for 72 hours would reduce the risk of death and moderate to severe neurodevelopmental injury at 18-22 months corrected age. Infants at least 36 weeks gestation with an abnormal blood gas within 1 hour of birth, or a history of an acute perinatal event and a 10-min Apgar score <5, or continued need for ventilation were screened. Following a neurological exam, those with moderate to severe encephalopathy were randomized to a 72-hour period of total body cooling (cooling blanket, followed by slow re-warming). The study was conducted in two phases: Phase I (20 infants) were examined for the safety of an esophageal temperature of 34-35 C; Phase II (main trial, 200 infants) were evaluated for the safety and efficacy of an esophageal temperature of 33-34 C. Cardio-respiratory, electroencephalograms (EEGs), renal, metabolic, and hematologic status, and esophageal and abdominal skin temperature were monitored during the 72 hours of intervention.
Neurodevelopmental outcome was assessed at 18-22 mos of age by masked certified examiners. The outcome at 18-22 months showed that whole-body cooling reduces the risk of death or moderate to severe disability in infants with hypoxic ischemic encephalopathy.
Surviving infants were assessed at 6-7 years (school age).
Sponsor: NICHD Neonatal Research Network
Current Primary Outcome: Death or moderate or severe disability [ Time Frame: 18-22 months corrected age ]
Original Primary Outcome:
Current Secondary Outcome:
- Length of hospital stay [ Time Frame: Until discharge ]
- Frequency of multi-organ dysfunction [ Time Frame: Until discharge ]
- Withdrawal of support [ Time Frame: Until discharge ]
- Post-neonatal deaths [ Time Frame: 18-22 months corrected age ]
- Multiple disability [ Time Frame: 18-22 months corrected age ]
- Seizure disorders [ Time Frame: 18-22 months corrected age ]
- Rehospitalizations [ Time Frame: 18-22 months corrected age ]
Original Secondary Outcome:
Information By: NICHD Neonatal Research Network
Dates:
Date Received: June 1, 2000
Date Started: October 1999
Date Completion:
Last Updated: June 3, 2015
Last Verified: June 2015
