Late Hypothermia for Hypoxic-Ischemic Encephalopathy
Condition: Infant, Newborn; Hypoxia, Brain; Hypoxia-Ischemia, Brain; Encephalopathy, Hypoxic-Ischemic; Hypoxic-Ischemic Encephalopathy; Ischemic-Hypoxic Encephalopathy
MeSH terms: Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Hypoxia, Brain; Ischemia; Hypoxia; Hypothermia
Study type: Interventional

Summary: 
      This study is a randomized, placebo-controlled, clinical trial to evaluate whether induced
      whole-body hypothermia initiated between 6-24 hours of age and continued for 96 hours in
      infants ≥ 36 weeks gestational age with hypoxic-ischemic encephalopathy will reduce the
      incidence of death or disability at 18-22 months of age. The study will enroll 168 infants
      with signs of hypoxic-ischemic encephalopathy at 16 NICHD Neonatal Research Network sites,
      and randomly assign them to either receive hypothermia or participate in a non-cooled control
      group.
    

Detailed description: 
      Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized
      by acute or subacute brain injury due to asphyxia. In most cases the underlying cause and
      timing of injury are unknown, but many cases are 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.

      The incidence of long-term complications depends on the severity of HIE. Up to 80 percent of
      infants who survive stage 3 HIE develop significant long-term neurological disabilities -
      mental retardation, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or
      quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are
      normal.

      Because animal data suggests that brain injury from HIE evolves over several hours to days
      after the initial asphyxic insult, induced hypothermia holds promise as a neuroprotective
      therapy. Additional trials are needed to help define the most effective cooling strategies.

      With this in mind, and knowing that many babies with HIE arrive at neonatal intensive care
      units several hours after birth, this study will evaluate the safety and efficacy of
      initiating hypothermia 6-24 hours after birth.

      Study subjects: Infants born at 36 0/7ths weeks or greater gestational age that have been
      diagnosed with neonatal depression, perinatal asphyxia, or encephalopathy. The goal is to
      enroll 168 subjects.

      Stratification: After informed consent is obtained, infants will be randomized to either a
      hypothermia arm (with a target esophageal temperature of 33.5°C) or a control arm (37.0°C)
      for 96 hours. Enrolled infants will be stratified by age of enrollment (≤ 12 and > 12 hours)
      and stage of encephalopathy (moderate or severe).

      Informed Consent: Parents of eligible infants will be approached for consent to enroll in the
      study if the infant has a high probability of acute hemodynamic compromise, as defined above.
      Subsequent screening will determine whether the infant meets all inclusion criteria.

      Randomization: eligible and consented infants will be randomly assigned to either a
      hypothermia intervention group, or a non-cooled (control) group.

      Study Intervention: Induced whole-body hypothermia (with a target esophageal temperature of
      33.5°C) or a control group (37.0°C) for 96 hours.

      Interim Study Interruptions: None to date.

      Secondary Study includes determining an association between MRI detectable injury and
      neurodevelopment at 18-22 months.
    

Intervention name(s): Hypothermia; Normothermic Control
Intervention type(s): Procedure; Procedure
Intervention description(s): Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours; Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: NICHD Neonatal Research Network; Hypoxic-ischemic encephalopathy (HIE); Hypothermia; Neonatal depression; Perinatal asphyxia