Overview

This trial is active, not recruiting.

Conditions infant, newborn, hypoxia, brain, hypoxia-ischemia, brain, encephalopathy, hypoxic-ischemic, hypoxic-ischemic encephalopathy, ischemic-hypoxic encephalopathy
Treatments hypothermia, normothermic control
Phase phase 2/phase 3
Sponsor NICHD Neonatal Research Network
Collaborator National Center for Research Resources (NCRR)
Start date April 2008
End date July 2016
Trial size 168 participants
Trial identifier NCT00614744, 1U10HD068263-01, NICHD-NRN-0038, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD036790, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, U10HD068244, U10HD068270, U10HD068278, U10HD068284, UL1RR024139, UL1RR024979, UL1RR025744

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 18-24 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
hypothermia
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
(Active Comparator)
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
normothermic control
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

Primary Outcomes

Measure
Death or moderate or severe disability
time frame: Birth to 18-24 months corrected gestational age

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants up to 24 hours old.

Inclusion Criteria: - Infants born at 36 0/7ths weeks gestational age or greater (by best obstetrical estimate) - Postnatal age between 6 and 24 hours following birth - Infants with a high probability of acute hemodynamic compromise, such as those with: - An acute perinatal event (abruptio placenta, cord prolapse, severe FHR abnormality) - An Apgar score ≤ 5 at 10 minutes - Continued need for ventilation initiated at birth for at least 10 minutes - Cord pH or first postnatal blood gas pH at ≤ 1 hour of ≤ 7.0 - Base deficit on cord gas or first postnatal blood gas at ≤ 1 hour of ≥ 16 mEq/L - Infants matching the above criteria who also have an abnormal neurological exam showing the presence of moderate or severe encephalopathy - Infants whose parents/legal guardians have provided consent for enrollment. NOTE: These inclusion criteria are identical to the NICHD Neonatal Research Network's 2005 Hypothermia study (see links below), except for the time of entry (6-24 hours vs. < 6 hours of age). Exclusion Criteria: - Any infant with a core body temperature (axilla, rectal) less than 34.0°C for greater than 1 hour - Presence of a known anomaly or chromosomal aberration - Birth weight < 1,800 grams - Infant in extremis - Infants whose parents/legal guardians or attending physician refuse consent

Additional Information

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 Research Network
Principal investigator Abbot R. Laptook, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by NICHD Neonatal Research Network.