Infant, NewbornNCT01192776

Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)

A study testing Whole-body Cooling in people with Infant, Newborn and Hypoxia, Brain, run by NICHD Neonatal Research Network at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 6 hours
Conditions the study is for: Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain
What is being tested?: Whole-body Cooling
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 364 participants
Where: 19 sitesUnited States
Study dates: Sep 2010to Mar 2016
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 6 hours
All sexes
No healthy volunteers
Child

Who may be able to join

Eligibility will be determined in a stepped process:
All infants with a gestational age ≥ 36 weeks will be screened for study entry if they are admitted to the NICU with a diagnosis of fetal acidosis, perinatal asphyxia, neonatal depression or encephalopathy.
Infants will be eligible if:
They have a pH ≤ 7.0 or a base deficit ≥ 16m mEq/ L on umbilical cord or any postnatal sample within 1 hour of age.
If, during this interval, they have a pH between 7.01 and 7.15, a base deficit is between 10 and 15.9 mEq/L, or a blood gas is not available, AND they have an acute perinatal event AND either a 10-minute Apgar score ≤ 5 or assisted ventilation initiated at birth and continued for at least 10 minutes.
Once these criteria are met, eligible infants will have a standardized neurological examination performed by a certified physician examiner. Infants will be candidates for the study when encephalopathy or seizures are present. For this study, encephalopathy is defined as the presence of 1 or more signs in 3 of the following 6 categories:

Show all 13Show fewer

Level of consciousness: lethargy, stupor or coma;
Spontaneous activity: decreased, absent;
Posture: distal flexion, decerebrate;
tone: hypotonia, flaccid or hypertonia, rigid;
Primitive reflexes: a) suck, weak, absent; b) Moro, incomplete, flaccid;
Autonomic nervous system: a) pupils: constricted, unequal, skew deviation or non reactive to light; b) heart rate: bradycardia, variable heart rate or c) respiration: periodic breathing, apnea.
Eligible infants from multiple births will be enrolled in the same arm of the study.

Who cannot join

Inability to randomize by 6 hours of age
Major congenital abnormality
Major chromosomal abnormality (including Trisomy 21),
Severe growth restriction (≤ 1800gm birth weight),
Infant is moribund and will not receive any further aggressive treatment,
Refusal of consent by parent
Refusal of consent by attending neonatologist
Infants with a core temperature < 33.5°C for > 1 hour at the time of screening by the research team would not be eligible for the study.

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of California - Los Angeles
Los Angeles, California, 90025
Stanford University
Palo Alto, California, 94304
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642

Other trials in United States

About this study

Official title: Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy

The Optimizing Cooling trial will compare four whole-body cooling treatments for infants born at 36 weeks gestational age or later with hypoxic-ischemic encephalopathy: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. The objective of this study is to evaluate whether whole-body cooling initiated at less than 6 hours of age and continued for 120 hours and/or a depth at 32.0°C in will reduce death and disability at 18-22 months corrected age.

Read the detailed description

Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by brain injury due to asphyxia 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. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term disabilities, including intellectual disabilities, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.

Previous studies have shown treatment with hypothermia to be an effective therapy for HIE. Currently, infants diagnosed with HIE at less than six hours of age are given whole-body cooling, decreasing their core body temperature to 33.5°C (93.2° Fahrenheit) for a period 72 hours using a cooling blanket. This treatment appears to protect the brain, decreasing the rate of death and disability and improving the chances of survival and neurodevelopmental outcomes at 18 months correct age. But additional trials are needed to help define the most effective cooling strategies.

The Optimizing Cooling trial will examine whether cooling for a longer time period and/or to a lower temperature will improve the chance of survival and neurodevelopmental outcomes at 18-22 months corrected age. Eligible infants with HIE will be placed in one of four cooling groups: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. Infants will be monitored closely and receive the care of the Neonatal Intensive Care Unit (NICU).

Infants enrolled in the study will be placed on a cooling blanket - the same type of blanket children's hospitals use in the NICU, in operating rooms during surgeries, and to cool children with high fevers. Each infant will be cooled according to the study group he or she is assigned to. During cooling, the infant's temperature will be very closely monitored by continuous esophageal (core)temperature readings. This will be done by placing a soft, narrow, flexible plastic tube into the infant's nose and down to just above the stomach. Skin temperatures will also be monitored closely. At the end of the assigned period of cooling, the infant will be slowly re-warmed until a normal core temperature of 36.5 to 37.0°C (97.7 to 98.6°C) is reached.

Infants will be examined at 18-22 months corrected age to assess their neurodevelopmental outcomes.

Secondary Studies include:

Using aEEG to 1)predict mortality or moderate to severe disability at 18-22 months in term infants with HIE treated with systemic hypothermia and 2) to record electrical seizure activity to compare rewarming initiated at 72 hours and later rewarming that is initiated at 120 hours.
Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.

Conditions: Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain, Encephalopathy, Hypoxic-Ischemic, Hypoxic-Ischemic Encephalopathy, Ischemic-Hypoxic Encephalopathy
Being tested: Whole-body Cooling
Keywords: NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia, Fetal acidosis
Medical subject headings: Hypoxia, Brain, Hypoxia-Ischemia, Brain, Hypothermia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Whole-body CoolingProcedure or surgery
Also called Blanketrol II Model 222R, Blanketrol III Model 233 (used in the II mode)
Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Study groups in NCT01192776
Study group	Role	What they receive
33.5°C for 72 hours	Active comparator	Target Temp: 33.5°C Duration: 72 hrs Receives: Procedure: Whole-body Cooling
33.5°C for 120 hours	Experimental	Target Temp: 33.5°C Duration: 120 hrs Receives: Procedure: Whole-body Cooling
32.0°C for 72 hours	Experimental	Target Temp: 32.0°C Duration: 72 hrs Receives: Procedure: Whole-body Cooling
32.0°C for 120 hours	Experimental	Target Temp: 32.0°C Duration:120 hrs Receives: Procedure: Whole-body Cooling

What is being measured

The primary outcome is the main question the study is designed to answer.

Death or Moderate to Severe Disability
Death includes any mortality prior to follow up at 18-22 months. Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands.
Measured: Birth to 22 months corrected age

Secondary outcomes (11)

Death
Death includes any mortality prior to follow up at 18-22 months.
Measured: Birth to 22 months corrected age
Level of Disability Among Survivors
Among survivors number of normal infants and infants with mild, moderate, and severe disability
Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge.
Measured: Follow up at 18-22 months corrected age
Withdrawal of Care
Number of infants for whom aggressive care is withdrawn
Measured: Birth through hospital discharge, average 22 days.
Clinical Neonatal Seizures
Documented seizures during hospital course
Measured: Through death, discharge, or transfer
Bayley Cognitive Score
Bayley Scale of Infant Development Composite Cognitive Score. The total composite score is reported, ranging from the lowest score of 55 to the highest score of 145. Lower values specify worse outcome.
Measured: Follow up at 18-22 months corrected age
Cerebral Palsy
Measured: Follow up at 18-22 months corrected age
Level of Disability Among Survivors, by Level of HIE
Among survivors, number of normal infants and infants with mild, moderate and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge.
Measured: Follow up at 18-22 months corrected age
Visual Impairment
Visual impairment is defined as bilateral blindness with some/no useful vision
Measured: Follow up at 18-22 months corrected age
Hearing Impairment
Hearing impairment is defined as hearing impairment despite amplification
Measured: Follow up at 18-22 months corrected age
Multiple Disabilities
Multiple disabilities is defined as two or more of the following 5 components: disabling CP, GMFCS level 3-5, Bayley cognitive score < 70, blindness, or deafness.
Measured: Follow up at 18-22 months corrected age
Multiorgan Dysfunction
The data needed for this analysis are not collected directly, and will not be analyzed as the study was terminated early and no funds available to complete this complex analysis. The data for this study will be stored at the NICHD-DASH for investigators.
Measured: Until death, discharge, or transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2010Mar 2016

First posted1 Sep 2010 (estimated)
Study startSep 2010
Primary completionMar 2016
Study completionMar 2016

Why it stopped: The trial closed for emerging safety profile and futility analysis and will not resume.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (9)Papers the sponsor has linked to this study.
Other trials for Infant, NewbornStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Enrolment: 364 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01192776
Sponsor's protocol ID: NICHD-NRN-0043
Other IDs: U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880
Status last verified: Jun 2026
First submitted: 31 Aug 2010
Last updated: 24 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Shankaran S, Laptook AR, Guimaraes C, Murnick J, McDonald SA, Das A, Petrie Huitema CM, Pappas A, Higgins RD, Hintz SR, Zaterka-Baxter KM, Van Meurs KP, Sokol GM, Chalak LF, Colaizy TT, Devaskar U, Tyson JE, Reynolds AM, DeMauro SB, Sanchez PJ, Laughon MM, Carlo WA, Watterberg K, Puopolo KM, Hibbs AM, Hamrick SEG, Cotten CM, Barks J, Poindexter BB, Truog WE, D'Angio CT; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. NICHD Magnetic Resonance Brain Imaging Score in Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2025 Apr 1;179(4):383-395. doi: 10.1001/jamapediatrics.2024.6209.
PubMed 39960680
Bonifacio SL, Chalak LF, Van Meurs KP, Laptook AR, Shankaran S. Neuroprotection for hypoxic-ischemic encephalopathy: Contributions from the neonatal research network. Semin Perinatol. 2022 Nov;46(7):151639. doi: 10.1016/j.semperi.2022.151639. Epub 2022 Jun 10.
PubMed 35835616
Shukla VV, Bann CM, Ramani M, Ambalavanan N, Peralta-Carcelen M, Hintz SR, Higgins RD, Natarajan G, Laptook AR, Shankaran S, Carlo WA. Predictive Ability of 10-Minute Apgar Scores for Mortality and Neurodevelopmental Disability. Pediatrics. 2022 Apr 1;149(4):e2021054992. doi: 10.1542/peds.2021-054992.
PubMed 35296895
Chalak LF, Pappas A, Tan S, Das A, Sanchez PJ, Laptook AR, Van Meurs KP, Shankaran S, Bell EF, Davis AS, Heyne RJ, Pedroza C, Poindexter BB, Schibler K, Tyson JE, Ball MB, Bara R, Grisby C, Sokol GM, D'Angio CT, Hamrick SEG, Dysart KC, Cotten CM, Truog WE, Watterberg KL, Timan CJ, Garg M, Carlo WA, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study. JAMA Neurol. 2021 Dec 1;78(12):1484-1493. doi: 10.1001/jamaneurol.2021.3723.
PubMed 34882200
Ambalavanan N, Shankaran S, Laptook AR, Carper BA, Das A, Carlo WA, Cotten CM, Duncan AF, Higgins RD; EUNICE KENNEDY SHRIVER NICHD NEONATAL RESEARCH NETWORK. Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy. Pediatrics. 2021 Jun;147(6):e2020048678. doi: 10.1542/peds.2020-048678. Epub 2021 May 13.
PubMed 33986149
Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Huitema CMP, Grisby C, Devaskar U, Ehrenkranz RA, Harmon HM, Chalak LF, DeMauro SB, Garg M, Hartley-McAndrew ME, Khan AM, Walsh MC, Ambalavanan N, Brumbaugh JE, Watterberg KL, Shepherd EG, Hamrick SEG, Barks J, Cotten CM, Kilbride HW, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):57-67. doi: 10.1001/jama.2017.7218.
PubMed 28672318
Pedroza C, Tyson JE, Das A, Laptook A, Bell EF, Shankaran S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial. Trials. 2016 Jul 22;17(1):335. doi: 10.1186/s13063-016-1480-4.
PubMed 27450203
Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Grisby C, Huitema CM, Garg M, Ehrenkranz RA, Shepherd EG, Chalak LF, Hamrick SE, Khan AM, Reynolds AM, Laughon MM, Truog WE, Dysart KC, Carlo WA, Walsh MC, Watterberg KL, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA. 2014 Dec 24-31;312(24):2629-39. doi: 10.1001/jama.2014.16058.
PubMed 25536254
Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.
PubMed 24524452

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy
ClinicalTrials.gov ID: NCT01192776
Acronym / sponsor ID: NICHD-NRN-0043
Conditions: Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain, Encephalopathy, Hypoxic-Ischemic, Hypoxic-Ischemic Encephalopathy, Ischemic-Hypoxic Encephalopathy
Keywords: NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia, Fetal acidosis
Study type: Interventional
Recruitment status: TerminatedReason stopped: The trial closed for emerging safety profile and futility analysis and will not resume.
Enrolment: 364 participants (actual)
Lead sponsor: NICHD Neonatal Research NetworkResearch network
Collaborators: National Center for Research Resources (NCRR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Sep 2010
Primary completion: Mar 2016 (actual)
Study completion: Mar 2016 (actual)
First posted: 1 Sep 2010 (estimated)
Results: Posted 15 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Infants will be examined at 18-22 months corrected age to assess their neurodevelopmental outcomes.

Secondary Studies include:

Using aEEG to 1)predict mortality or moderate to severe disability at 18-22 months in term infants with HIE treated with systemic hypothermia and 2) to record electrical seizure activity to compare rewarming initiated at 72 hours and later rewarming that is initiated at 120 hours.
Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
33.5°C for 72 hours	Active comparator	Procedure: Whole-body CoolingTarget Temp: 33.5°C Duration: 72 hrs
33.5°C for 120 hours	Experimental	Procedure: Whole-body CoolingTarget Temp: 33.5°C Duration: 120 hrs
32.0°C for 72 hours	Experimental	Procedure: Whole-body CoolingTarget Temp: 32.0°C Duration: 72 hrs
32.0°C for 120 hours	Experimental	Procedure: Whole-body CoolingTarget Temp: 32.0°C Duration:120 hrs

Who may qualify

Ages: Up to 6 hours
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (13 listed)

All infants with a gestational age ≥ 36 weeks will be screened for study entry if they are admitted to the NICU with a diagnosis of fetal acidosis, perinatal asphyxia, neonatal depression or encephalopathy.
Infants will be eligible if:
Once these criteria are met, eligible infants will have a standardized neurological examination performed by a certified physician examiner. Infants will be candidates for the study when encephalopathy or seizures are present. For this study, encephalopathy is defined as the presence of 1 or more signs in 3 of the following 6 categories:
Eligible infants from multiple births will be enrolled in the same arm of the study.

Key exclusion criteria (8 listed)

Inability to randomize by 6 hours of age
Major congenital abnormality
Major chromosomal abnormality (including Trisomy 21),
Severe growth restriction (≤ 1800gm birth weight),
Infant is moribund and will not receive any further aggressive treatment,

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Whole-body CoolingAlso: Blanketrol II Model 222R, Blanketrol III Model 233 (used in the II mode)Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.	Procedure or surgery	32.0°C for 120 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, 33.5°C for 72 hours

Primary outcome

Death or Moderate to Severe Disability
Time frame: Birth to 22 months corrected age
Death includes any mortality prior to follow up at 18-22 months. Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands.

11 secondary outcomes

Death
Time frame: Birth to 22 months corrected age
Level of Disability Among Survivors
Time frame: Follow up at 18-22 months corrected age
Withdrawal of Care
Time frame: Birth through hospital discharge, average 22 days.
Clinical Neonatal Seizures
Time frame: Through death, discharge, or transfer
Bayley Cognitive Score
Time frame: Follow up at 18-22 months corrected age
Cerebral Palsy
Time frame: Follow up at 18-22 months corrected age
Level of Disability Among Survivors, by Level of HIE
Time frame: Follow up at 18-22 months corrected age
Visual Impairment
Time frame: Follow up at 18-22 months corrected age
Hearing Impairment
Time frame: Follow up at 18-22 months corrected age
Multiple Disabilities
Time frame: Follow up at 18-22 months corrected age
Multiorgan Dysfunction
Time frame: Until death, discharge, or transfer

Results and safety

Results posted to the registry on 15 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
33.5°C for 72 Hours	95	84
32.0°C for 72 Hours	90	69
33.5°C for 120 Hours	96	75
32.0°C for 120 Hours	83	63

Primary outcome: Death or Moderate to Severe Disability

Time frame: Birth to 22 months corrected age. Count of participants. Unit: Participants

Measure	33.5°C for 72 Hours n = 92	32.0°C for 72 Hours n = 84	33.5°C for 120 Hours n = 93	32.0°C for 120 Hours n = 78
Value	27	29	32	22

33.5°C for 72 Hours vs 32.0°C for 72 Hours: Risk Ratio (RR): 1.23 (95% CI 0.76 to 1.98)
33.5°C for 72 Hours vs 33.5°C for 120 Hours: Risk Ratio (RR): 1.21 (95% CI 0.78 to 1.87)
33.5°C for 72 Hours vs 32.0°C for 120 Hours: Risk Ratio (RR): 0.85 (95% CI 0.53 to 1.35)

Population analysed: Includes all deaths and all infants followed at 18-22 months. Does not include 17 infants lost to follow up.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: During study intervention period: 72 or 120 hours from baseline, based on treatment arm. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
33.5°C for 72 Hours	10 of 95 (10.5%)	5 of 95 (5.3%)	8 of 92
32.0°C for 72 Hours	15 of 90 (16.7%)	3 of 90 (3.3%)	15 of 84
33.5°C for 120 Hours	11 of 96 (11.5%)	6 of 96 (6.3%)	18 of 93
32.0°C for 120 Hours	23 of 83 (27.7%)	9 of 83 (10.8%)	15 of 78

Limitations and caveats (from the sponsor): This RCT was stopped for safety and futility reasons by the Data Safety and Monitoring Committee so did not enroll the target number of participants needed to achieve target power and statistically reliable results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39960680Shankaran S, Laptook AR, Guimaraes C, Murnick J, McDonald SA, Das A, Petrie Huitema CM, Pappas A, Higgins RD, Hintz SR, Zaterka-Baxter KM, Van Meurs KP, Sokol GM, Chalak LF, Colaizy TT, Devaskar U, Tyson JE, Reynolds AM, DeMauro SB, Sanchez PJ, Laughon MM, Carlo WA, Watterberg K, Puopolo KM, Hibbs AM, Hamrick SEG, Cotten CM, Barks J, Poindexter BB, Truog WE, D'Angio CT; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. NICHD Magnetic Resonance Brain Imaging Score in Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2025 Apr 1;179(4):383-395. doi: 10.1001/jamapediatrics.2024.6209.
Derived from this study: PubMed 35835616Bonifacio SL, Chalak LF, Van Meurs KP, Laptook AR, Shankaran S. Neuroprotection for hypoxic-ischemic encephalopathy: Contributions from the neonatal research network. Semin Perinatol. 2022 Nov;46(7):151639. doi: 10.1016/j.semperi.2022.151639. Epub 2022 Jun 10.
Derived from this study: PubMed 35296895Shukla VV, Bann CM, Ramani M, Ambalavanan N, Peralta-Carcelen M, Hintz SR, Higgins RD, Natarajan G, Laptook AR, Shankaran S, Carlo WA. Predictive Ability of 10-Minute Apgar Scores for Mortality and Neurodevelopmental Disability. Pediatrics. 2022 Apr 1;149(4):e2021054992. doi: 10.1542/peds.2021-054992.
Derived from this study: PubMed 34882200Chalak LF, Pappas A, Tan S, Das A, Sanchez PJ, Laptook AR, Van Meurs KP, Shankaran S, Bell EF, Davis AS, Heyne RJ, Pedroza C, Poindexter BB, Schibler K, Tyson JE, Ball MB, Bara R, Grisby C, Sokol GM, D'Angio CT, Hamrick SEG, Dysart KC, Cotten CM, Truog WE, Watterberg KL, Timan CJ, Garg M, Carlo WA, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study. JAMA Neurol. 2021 Dec 1;78(12):1484-1493. doi: 10.1001/jamaneurol.2021.3723.
Derived from this study: PubMed 33986149Ambalavanan N, Shankaran S, Laptook AR, Carper BA, Das A, Carlo WA, Cotten CM, Duncan AF, Higgins RD; EUNICE KENNEDY SHRIVER NICHD NEONATAL RESEARCH NETWORK. Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy. Pediatrics. 2021 Jun;147(6):e2020048678. doi: 10.1542/peds.2020-048678. Epub 2021 May 13.
Derived from this study: PubMed 28672318Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Huitema CMP, Grisby C, Devaskar U, Ehrenkranz RA, Harmon HM, Chalak LF, DeMauro SB, Garg M, Hartley-McAndrew ME, Khan AM, Walsh MC, Ambalavanan N, Brumbaugh JE, Watterberg KL, Shepherd EG, Hamrick SEG, Barks J, Cotten CM, Kilbride HW, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Jul 4;318(1):57-67. doi: 10.1001/jama.2017.7218.
Derived from this study: PubMed 27450203Pedroza C, Tyson JE, Das A, Laptook A, Bell EF, Shankaran S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial. Trials. 2016 Jul 22;17(1):335. doi: 10.1186/s13063-016-1480-4.
Derived from this study: PubMed 25536254Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, Pedroza C, Bara R, Van Meurs KP, Grisby C, Huitema CM, Garg M, Ehrenkranz RA, Shepherd EG, Chalak LF, Hamrick SE, Khan AM, Reynolds AM, Laughon MM, Truog WE, Dysart KC, Carlo WA, Walsh MC, Watterberg KL, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA. 2014 Dec 24-31;312(24):2629-39. doi: 10.1001/jama.2014.16058.
Derived from this study: PubMed 24524452Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.
Neonatal Research Network websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Seetha Shankaran, MD study chair

Wayne State University

Abbot R Laptook, MD principal investigator

Brown University, Women & Infants Hospital of Rhode Island

Michele C Walsh, MD MS principal investigator

Case Western Reserve University, Rainbow Babies and Children's Hospital

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Whole-body Cooling in people with Infant, Newborn and Hypoxia, Brain, run by NICHD Neonatal Research Network at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or Moderate to Severe Disability (time frame: Birth to 22 months corrected age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01192776, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.