Whole-Body Cooling for Birth Asphyxia in Term Infants

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00005772
First received: June 1, 2000
Last updated: November 4, 2011
Last verified: September 2011
  Purpose

This large multicenter trial tested whether cerebral cooling initiated within 6 hours of birth and continued for 72 hours would reduce the risk of death and moderate to severe neurodevelopmental injury at 18-22 months corrected age. Infants at least 36 weeks gestation with an abnormal blood gas within 1 hour of birth, or a history of an acute perinatal event and a 10-min Apgar score <5, or continued need for ventilation were screened. Following a neurological exam, those with moderate to severe encephalopathy were randomized to a 72-hour period of total body cooling (cooling blanket, followed by slow re-warming). The study was conducted in two phases: Phase I (20 infants) were examined for the safety of an esophageal temperature of 34-35 C; Phase II (main trial, 200 infants) were evaluated for the safety and efficacy of an esophageal temperature of 33-34 C. Cardio-respiratory, electroencephalograms (EEGs), renal, metabolic, and hematologic status, and esophageal and abdominal skin temperature were monitored during the 72 hours of intervention. Surviving children were given neurodevelopmental examinations at 18-22 months corrected age and again at school age (6-7 years of age).


Condition Intervention Phase
Infant, Newborn
Hypoxia-Ischemia, Brain
Device: Induced hypothermia
Device: Control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Hypothermia for Hypoxic-Ischemic Encephalopathy in Term Infants

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: 18-22 months corrected age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Length of hospital stay [ Time Frame: Until discharge ] [ Designated as safety issue: No ]
  • Frequency of multi-organ dysfunction [ Time Frame: Until discharge ] [ Designated as safety issue: Yes ]
  • Withdrawal of support [ Time Frame: Until discharge ] [ Designated as safety issue: Yes ]
  • Post-neonatal deaths [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Multiple disability [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Seizure disorders [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Rehospitalizations [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]

Enrollment: 208
Study Start Date: October 1999
Study Completion Date: July 2010
Primary Completion Date: May 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypothermia
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Device: Induced hypothermia
Whole-body cooling using the Blanketrol II or III Units in the Automatic Control Mode with a YSI 400 series temperature probe placed in the distal esophagus over a 96-hour period
Placebo Comparator: Normothermic
Placebo: Normothermic control group (with esophageal temperature at or near 37.0°C) for 96 hours
Device: Control
Control group: standard care

Detailed Description:

Perinatal cerebral hypoxia-ischemia injury is an important cause of death and neurodevelopmental disability. Data from animal models suggest that brain cooling immediately after injury is neuroprotective. Experience with total body cooling during surgery, accidental near drownings, and one Phase I trial of term infants suggest that it is effective and safe in children.

This large multicenter trial tested whether cerebral cooling initiated within 6 hours of birth and continued for 72 hours would reduce the risk of death and moderate to severe neurodevelopmental injury at 18-22 months corrected age. Infants at least 36 weeks gestation with an abnormal blood gas within 1 hour of birth, or a history of an acute perinatal event and a 10-min Apgar score <5, or continued need for ventilation were screened. Following a neurological exam, those with moderate to severe encephalopathy were randomized to a 72-hour period of total body cooling (cooling blanket, followed by slow re-warming). The study was conducted in two phases: Phase I (20 infants) were examined for the safety of an esophageal temperature of 34-35 C; Phase II (main trial, 200 infants) were evaluated for the safety and efficacy of an esophageal temperature of 33-34 C. Cardio-respiratory, electroencephalograms (EEGs), renal, metabolic, and hematologic status, and esophageal and abdominal skin temperature were monitored during the 72 hours of intervention.

Neurodevelopmental outcome was assessed at 18-22 mos of age by masked certified examiners. The outcome at 18-22 months showed that whole-body cooling reduces the risk of death or moderate to severe disability in infants with hypoxic ischemic encephalopathy.

Surviving infants were assessed at 6-7 years (school age).

  Eligibility

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 36 weeks gestation
  • Any blood gas (cord, postnatal) done within the first 60 minutes had a pH less than or equal to 7.0
  • Any blood gas (cord postnatal) done within the first 60 minutes had a base deficit greater than or equal to 16 mEq/L
  • All infants must have seizures or signs of moderate to severe encephalopathy before randomization

Exclusion Criteria:

  • Inability to randomize by 6 hours of age
  • Presence of known chromosomal anomaly or major congenital anomaly
  • Severe intrauterine growth restriction (weight less than 1800g)
  • All blood gases done within the first 60 minutes had a pH less than 7.15 and a base deficit less than 10 mEq/L
  • Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
  • Parents refuse consent
  • Attending neonatologist refuses 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: NCT00005772

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Harvard University
Cambridge, Massachusetts, United States, 02138
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
RTI International
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Abbot R. Laptook, MD Brown University, Womens and Infants Hospital of Rhode Island
Principal Investigator: Michele C. Walsh, MD MS Case Western Reserve University
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
Study Director: Krisa P. Van Meurs, MD Stanford University
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Neil N. Finer, MD University of California, San Diego
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Shahnaz Duara, MD University of Miami
Principal Investigator: Dale L. Phelps, MD University of Rochester
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: T. Michael O'Shea, MD Wake Forest School of Medicine
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00005772     History of Changes
Other Study ID Numbers: NICHD-NRN-0021, U10HD021364, U10HD021373, U10HD021385, U10HD021397, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD040461, U10HD040492, U10HD040498, U10HD040521, U10HD040689, M01RR000030, M01RR000039, M01RR000044, M01RR000070, M01RR000080, M01RR000633, M01RR000750, M01RR006022, M01RR007122, M01RR008084, M01RR016587
Study First Received: June 1, 2000
Last Updated: November 4, 2011
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:
Brain Ischemia
Hypoxia-Ischemia, Brain
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Hypoxia, Brain
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 21, 2014