Late Hypothermia for Hypoxic-Ischemic Encephalopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00614744
First received: February 11, 2008
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Infant, Newborn
Hypoxia, Brain
Hypoxia-Ischemia, Brain
Encephalopathy, Hypoxic-Ischemic
Hypoxic-Ischemic Encephalopathy
Ischemic-Hypoxic Encephalopathy
Procedure: Hypothermia
Procedure: Normothermic Control
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Death or moderate or severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]

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

Estimated Enrollment: 168
Study Start Date: April 2008
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Whole-body Hypothermia
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Procedure: Hypothermia
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Active Comparator: Normothermia
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Procedure: Normothermic Control
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

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.

  Eligibility

Ages Eligible for Study:   up to 24 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614744

Contacts
Contact: Abbot R. Laptook, MD (401) 274-1122 ext 43200
Contact: Rosemary D. Higgins, MD (301) 496-5575

  Show 22 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Abbot R. Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD Duke University
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Brenda B. Poindexter, MD MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Ivan D. Frantz III, MD Tufts Medical Center
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Edward F. Bell, MD University of Iowa
Principal Investigator: Kristi L. Watterberg, MD University of New Mexico
Principal Investigator: Pablo J. Sanchez, MD University of Texas Southwestern Medical Center at Dallas
Principal Investigator: Kathleen A. Kennedy, MD MPH The University of Texas Health Science Center, Houston
Principal Investigator: Roger G. Faix, MD University of Utah
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
Principal Investigator: William Truog, MD Children's Mercy Hospital-Kansas City, MO
Principal Investigator: Barbara Schmidt, MD, MSc University of Pennsylvania
Principal Investigator: Carl D'Angio, MD University of Rochester
Principal Investigator: Uday Devaskar, MD University of California, Los Angeles
Principal Investigator: Leif Nelin Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00614744     History of Changes
Other Study ID Numbers: NICHD-NRN-0038, U10HD036790, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, UL1RR024139, UL1RR025744, UL1RR024979, U10HD068244, 1U10HD068263-01, U10HD068270, U10HD068278, U10HD068284
Study First Received: February 11, 2008
Last Updated: September 26, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Hypoxic-ischemic encephalopathy (HIE)
Hypothermia
Neonatal depression
Perinatal asphyxia

Additional relevant MeSH terms:
Neurologic Manifestations
Hypoxia, Brain
Hypoxia-Ischemia, Brain
Brain Ischemia
Hypothermia
Ischemia
Brain Damage, Chronic
Delirium
Encephalitis
Hepatic Encephalopathy
Neurotoxicity Syndromes
Anoxia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Liver Failure
Hepatic Insufficiency

ClinicalTrials.gov processed this record on July 24, 2014