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Whole-Body Cooling for Birth Asphyxia in Term Infants

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ClinicalTrials.gov Identifier: NCT00005772
Recruitment Status : Completed
First Posted : June 2, 2000
Last Update Posted : March 22, 2019
Sponsor:
Collaborator:
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

Tracking Information
First Submitted Date  ICMJE June 1, 2000
First Posted Date  ICMJE June 2, 2000
Last Update Posted Date March 22, 2019
Study Start Date  ICMJE October 1999
Actual Primary Completion Date May 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2009)
Death or moderate or severe disability [ Time Frame: 18-22 months corrected age ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2009)
  • Length of hospital stay [ Time Frame: Until discharge ]
  • Frequency of multi-organ dysfunction [ Time Frame: Until discharge ]
  • Withdrawal of support [ Time Frame: Until discharge ]
  • Post-neonatal deaths [ Time Frame: 18-22 months corrected age ]
  • Multiple disability [ Time Frame: 18-22 months corrected age ]
  • Seizure disorders [ Time Frame: 18-22 months corrected age ]
  • Rehospitalizations [ Time Frame: 18-22 months corrected age ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Whole-Body Cooling for Birth Asphyxia in Term Infants
Official Title  ICMJE Randomized Controlled Trial of Hypothermia for Hypoxic-Ischemic Encephalopathy in Term Infants
Brief Summary 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).
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Infant, Newborn
  • Hypoxia-Ischemia, Brain
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 6, 2009)
208
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
200
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date May 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Hours   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005772
Other Study ID Numbers  ICMJE NICHD-NRN-0021
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD021397 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD040461 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD040498 ( U.S. NIH Grant/Contract )
U10HD040521 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
M01RR000030 ( U.S. NIH Grant/Contract )
M01RR000039 ( U.S. NIH Grant/Contract )
M01RR000044 ( U.S. NIH Grant/Contract )
M01RR000070 ( U.S. NIH Grant/Contract )
M01RR000080 ( U.S. NIH Grant/Contract )
M01RR000633 ( U.S. NIH Grant/Contract )
M01RR000750 ( U.S. NIH Grant/Contract )
M01RR006022 ( U.S. NIH Grant/Contract )
M01RR007122 ( U.S. NIH Grant/Contract )
M01RR008084 ( U.S. NIH Grant/Contract )
M01RR016587 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NICHD Neonatal Research Network
Study Sponsor  ICMJE NICHD Neonatal Research Network
Collaborators  ICMJE National Center for Research Resources (NCRR)
Investigators  ICMJE
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 Children's Hospital Medical Center, Cincinnati
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 University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
PRS Account NICHD Neonatal Research Network
Verification Date March 2019

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