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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

June 1, 2000
November 4, 2011
October 1999
May 2003   (final data collection date for primary outcome measure)
Death or moderate or severe disability [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00005772 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Whole-Body Cooling for Birth Asphyxia in Term Infants
Randomized Controlled Trial of Hypothermia for Hypoxic-Ischemic Encephalopathy in Term Infants

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).

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Infant, Newborn
  • Hypoxia-Ischemia, Brain
  • 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
  • Device: Control
    Control group: standard care
  • Experimental: Hypothermia
    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
    Intervention: Device: Induced hypothermia
  • Placebo Comparator: Normothermic
    Placebo: Normothermic control group (with esophageal temperature at or near 37.0°C) for 96 hours
    Intervention: Device: Control

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
208
July 2010
May 2003   (final data collection date for primary outcome measure)

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
Both
up to 6 Hours
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00005772
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
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP