Clinical Trial: Late Hypothermia for Hypoxic-Ischemic Encephalopathy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Evaluation of Systemic Hypothermia Initiated After 6 Hours of Age in Infants ≥36 Weeks Gestation With Hypoxic-Ischemic Encephalopathy: A Bayesian Evaluation. A Protocol for the NICHD Neonatal Re

Brief 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 Summary:

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, i
Sponsor: NICHD Neonatal Research Network

Current Primary Outcome: Death or moderate or severe disability [ Time Frame: Birth to 18-22 months corrected gestational age ]

Original Primary Outcome: Death or moderate or severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ]

Current Secondary Outcome:

  • Number of deaths in the NICU and following discharge [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with moderate and severe disability [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with mild, moderate and severe disability [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with any disability based on level of encephalopathy at randomization [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with non-CNS organ system dysfunction [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with a DNR order [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with a DNR order and support is withdrawn [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with a DNR order and either die or survive [ Time Frame: Birth to 18-22 months corrected gestational age ]
  • Number of infants with neonatal seizures, with and without EEG abnormalities [ Time Frame: Birth to 18-22 months corrected gestational age ]


Original Secondary Outcome:

  • Number of deaths in the NICU and following discharge [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with moderate and severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with mild, moderate and severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with any disability based on level of encephalopathy at randomization [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with non-CNS organ system dysfunction [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with a DNR order [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with a DNR order and support is withdrawn [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with a DNR order and either die or survive [ Time Frame: Birth to 18-24 months corrected gestational age ]
  • Number of infants with neonatal seizures, with and without EEG abnormalities [ Time Frame: Birth to 18-24 months corrected gestational age ]


Information By: NICHD Neonatal Research Network

Dates:
Date Received: February 11, 2008
Date Started: April 2008
Date Completion:
Last Updated: April 24, 2017
Last Verified: April 2017