Back to resultsWhole-Body Cooling for Birth Asphyxia in Term Infants
Primary Purpose
Infant, Newborn, Hypoxia-Ischemia, Brain
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Induced hypothermia
Control
Sponsored by
About this trial
This is an interventional treatment trial for Infant, Newborn focused on measuring NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham
- Stanford University
- Yale University
- University of Miami
- Emory University
- Indiana University
- Harvard University
- Wayne State University
- University of New Mexico
- RTI International
- Cincinnati Children's Medical Center
- Case Western Reserve University, Rainbow Babies and Children's Hospital
- Brown University, Women & Infants Hospital of Rhode Island
- University of Tennessee
- University of Texas Southwestern Medical Center at Dallas
- University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Hypothermia
Normothermic
Arm Description
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Placebo: Normothermic control group (with esophageal temperature at or near 37.0°C) for 96 hours
Outcomes
Primary Outcome Measures
Death or moderate or severe disability
Secondary Outcome Measures
Length of hospital stay
Frequency of multi-organ dysfunction
Withdrawal of support
Post-neonatal deaths
Multiple disability
Seizure disorders
Rehospitalizations
Full Information
NCT ID
NCT00005772
First Posted
June 1, 2000
Last Updated
March 20, 2019
Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00005772
Brief Title
Whole-Body Cooling for Birth Asphyxia in Term Infants
Official Title
Randomized Controlled Trial of Hypothermia for Hypoxic-Ischemic Encephalopathy in Term Infants
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
October 1999 (undefined)
Primary Completion Date
May 2003 (Actual)
Study Completion Date
July 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NICHD Neonatal Research Network
Collaborators
National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Newborn, Hypoxia-Ischemia, Brain
Keywords
NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
208 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hypothermia
Arm Type
Experimental
Arm Description
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Arm Title
Normothermic
Arm Type
Placebo Comparator
Arm Description
Placebo: Normothermic control group (with esophageal temperature at or near 37.0°C) for 96 hours
Intervention Type
Device
Intervention Name(s)
Induced hypothermia
Intervention Description
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
Intervention Type
Device
Intervention Name(s)
Control
Intervention Description
Control group: standard care
Primary Outcome Measure Information:
Title
Death or moderate or severe disability
Time Frame
18-22 months corrected age
Secondary Outcome Measure Information:
Title
Length of hospital stay
Time Frame
Until discharge
Title
Frequency of multi-organ dysfunction
Time Frame
Until discharge
Title
Withdrawal of support
Time Frame
Until discharge
Title
Post-neonatal deaths
Time Frame
18-22 months corrected age
Title
Multiple disability
Time Frame
18-22 months corrected age
Title
Seizure disorders
Time Frame
18-22 months corrected age
Title
Rehospitalizations
Time Frame
18-22 months corrected age
10. Eligibility
Sex
All
Maximum Age & Unit of Time
6 Hours
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seetha Shankaran, MD
Organizational Affiliation
Wayne State University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abbot R. Laptook, MD
Organizational Affiliation
Brown University, Womens and Infants Hospital of Rhode Island
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michele C. Walsh, MD MS
Organizational Affiliation
Case Western Reserve University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ronald N. Goldberg, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara J. Stoll, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brenda B. Poindexter, MD MS
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abhik Das, PhD
Organizational Affiliation
RTI International
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Krisa P. Van Meurs, MD
Organizational Affiliation
Stanford University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Waldemar A. Carlo, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neil N. Finer, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kurt Schibler, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shahnaz Duara, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dale L. Phelps, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pablo J. Sanchez, MD
Organizational Affiliation
University of Texas, Southwestern Medical Center at Dallas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathleen A. Kennedy, MD MPH
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
T. Michael O'Shea, MD
Organizational Affiliation
Wake Forest University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard A. Ehrenkranz, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Harvard University
City
Cambridge
State/Province
Massachusetts
ZIP/Postal Code
02138
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
RTI International
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cincinnati Children's Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University, Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Brown University, Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Tennessee
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
14510323
Citation
Shankaran S, Laptook A. Challenge of conducting trials of neuroprotection in the asphyxiated term infant. Semin Perinatol. 2003 Aug;27(4):320-32. doi: 10.1016/s0146-0005(03)00047-8.
Results Reference
background
PubMed Identifier
19281415
Citation
Shankaran S. Neonatal encephalopathy: treatment with hypothermia. J Neurotrauma. 2009 Mar;26(3):437-43. doi: 10.1089/neu.2008.0678.
Results Reference
background
PubMed Identifier
19762176
Citation
Higgins RD, Shankaran S. Hypothermia for hypoxic ischemic encephalopathy in infants > or =36 weeks. Early Hum Dev. 2009 Oct;85(10 Suppl):S49-52. doi: 10.1016/j.earlhumdev.2009.08.015. Epub 2009 Sep 17.
Results Reference
background
PubMed Identifier
16221780
Citation
Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005 Oct 13;353(15):1574-84. doi: 10.1056/NEJMcps050929.
Results Reference
result
PubMed Identifier
12165594
Citation
Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA, Stark AR, Tyson JE, Poole K, Carlo WA, Lemons JA, Oh W, Stoll BJ, Papile LA, Bauer CR, Stevenson DK, Korones SB, McDonald S. Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics. 2002 Aug;110(2 Pt 1):377-85. doi: 10.1542/peds.110.2.377.
Results Reference
result
PubMed Identifier
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Citation
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Citation
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Citation
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Results Reference
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Citation
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Citation
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Results Reference
derived
Links:
URL
http://neonatal.rti.org/
Description
NICHD Neonatal Research Network
Learn more about this trial
Whole-Body Cooling for Birth Asphyxia in Term Infants
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