Clinical Trial: Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy

Brief Summary: The Optimizing Cooling trial will compare four whole-body cooling treatments for infants born at 36 weeks gestational age or later with hypoxic-ischemic encephalopathy: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. The objective of this study is to evaluate whether whole-body cooling initiated at less than 6 hours of age and continued for 120 hours and/or a depth at 32.0°C in will reduce death and disability at 18-22 months corrected age.

Detailed Summary:

Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by brain injury due to asphyxia diagnosed at or shortly after birth. According to the World Health Organization, more than 722,000 children died from birth asphyxia and birth trauma worldwide in 2004. An estimated 50-75 percent of infants with severe (stage 3) HIE will die, with 55 percent of these deaths occurring in the first month. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term disabilities, including intellectual disabilities, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.

Previous studies have shown treatment with hypothermia to be an effective therapy for HIE. Currently, infants diagnosed with HIE at less than six hours of age are given whole-body cooling, decreasing their core body temperature to 33.5°C (93.2° Fahrenheit) for a period 72 hours using a cooling blanket. This treatment appears to protect the brain, decreasing the rate of death and disability and improving the chances of survival and neurodevelopmental outcomes at 18 months correct age. But additional trials are needed to help define the most effective cooling strategies.

The Optimizing Cooling trial will examine whether cooling for a longer time period and/or to a lower temperature will improve the chance of survival and neurodevelopmental outcomes at 18-22 months corrected age. Eligible infants with HIE will be placed in one of four cooling groups: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. Infants will be monitored closely and receive the care of the Neonatal Intensive Care U
Sponsor: NICHD Neonatal Research Network

Current Primary Outcome: Death or Moderate to Severe Disability [ Time Frame: Birth to 22 months corrected age ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Death [ Time Frame: Birth to 22 months corrected age ]
  • Mild, moderate, and severe disability [ Time Frame: 18-22 months corrected age ]
    Number of infants with mild, moderate, and severe disability
  • Withdrawal of care [ Time Frame: Birth to hospital discharge ]
    Number of infants for whom aggressive care is withdrawn
  • Acute Adverse Events [ Time Frame: Until infant achieves normothermia ]
    Number of adverse events (severe bradycardia, acidosis, bleeding or ischemic CNS abnormalities)
  • Clinical neonatal seizures [ Time Frame: Until death, discharge, or transfer ]
  • Severe neonatal brain abnormalities [ Time Frame: 7-14 days of life ]
    MRIs taken between 7-14 days will be examined.
  • Cognitive outcome [ Time Frame: 18-22 months corrected age ]
  • Cerebral palsy [ Time Frame: 18-22 months corrected age ]
  • Disability by stage of HIE [ Time Frame: 18-22 months corrected age ]
  • Visual impairment [ Time Frame: 18-22 months corrected age ]
  • Hearing impairment [ Time Frame: 18-22 months corrected age ]
  • Multiple Disabilities [ Time Frame: 18-22 months corrected age ]
  • Multiorgan Dysfunction [ Time Frame: Until death, discharge, or transfer ]


Original Secondary Outcome: Same as current

Information By: NICHD Neonatal Research Network

Dates:
Date Received: August 31, 2010
Date Started: September 2010
Date Completion:
Last Updated: January 23, 2017
Last Verified: January 2017