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CompletedNCT01793129Updated Nov 4, 2024Results posted

Preemie Hypothermia for Neonatal Encephalopathy

An interventional study of Hypothermia and Normothermic Control in Infant, Newborn, Hypoxia, Brain and Hypoxia-Ischemia, Brain, sponsored by NICHD Neonatal Research Network. Completed at 18 sites in United States. Open to participants aged 33 Weeks to 35 Weeks. Per ClinicalTrials.gov, last updated 2024-11-04.

Primary conditionHypoxia-Ischemia, BrainRegistry: Hypoxia, BrainReclassifiedWhy we changed it
Registry
Hypoxia, Brain — the first condition term the registry derived for this study.
ClinicalTrials.gg
Hypoxia-Ischemia, Brain
Why
  1. The study's listed conditions name Hypoxia-Ischemia, Brain, a narrower term within Hypoxia, Brain.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by NICHD Neonatal Research Network · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
168
Allocation
Randomized
Ages
33 Weeks to 35 Weeks
Sex
All
01

Study summary

This study is a randomized, controlled trial to assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at \<6 hours postnatal age with moderate to severe neonatal encephalopathy (NE). The study will enroll infants with signs of NE at 18 NICHD Neonatal Research Network sites, and randomly assign them to either receive hypothermia or participate in a non-cooled control group.

Read the detailed description

Most clinical studies of neonatal encephalopathy (NE) and potential interventions have focused on infants ≥36 weeks GA. Although many interventions have been suggested and assessed for prevention or palliation of NE, the only one currently supported by rigorous clinical evidence to improve outcome in human newborns has been hypothermia implemented at \<6 hours of postnatal age and maintained for 72 hrs. Data about diagnosis, frequency, severity, and outcome of NE in infants 33-35 weeks GA are sparse.

This trial will assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at \<6 hrs postnatal age with moderate to severe neonatal encephalopathy. Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate) and greater than or equal to 1500 grams birth weight (selected to minimize potential difficulties placing esophageal probe) who meet clinical, biochemical and neurologic criteria for moderate to severe NE will be randomized to either whole body hypothermia or participate in a non-cooled control group. The primary outcome will be death or moderate to severe disability at 18-22 months corrected age. The presence or absence of disability will be determined by the standard NRN interdisciplinary follow-up exam.

Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.

02

Conditions studied

  • Infant, Newborn
  • Hypoxia, Brain
  • Hypoxia-Ischemia, Brain
  • Encephalopathy, Hypoxic-Ischemic
  • Hypoxic-Ischemic Encephalopathy
  • Ischemic-Hypoxic Encephalopathy

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Keywords

  • NICHD Neonatal Research Network
  • Hypoxic-ischemic encephalopathy (HIE)
  • Hypothermia
  • Neonatal depression
  • Perinatal asphyxia
03

In context

Hypoxia-Ischemia, Brain Reclassified

261 studies on the registry are indexed under Hypoxia-Ischemia, Brain; 95 are open to participants now.

This study's enrollment of 168 is above the median of 50 across 156 interventional studies indexed under Hypoxia-Ischemia, Brain.

Browse Hypoxia-Ischemia, Brain studies →

Lead sponsor

NICHD Neonatal Research Network is the lead sponsor of 63 studies on the registry; 5 are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.

Compared within Hypoxia-Ischemia, Brain, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hypoxia, Brain. The counts are of registry records indexed under each term, refreshed daily. How we classify →

04

Who can participate

Ages eligible
33 Weeks to 35 Weeks
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate)
  • Infants weight greater than or equal to 1500 grams at birth
  • Postnatal age less than 6 hours
  • Infants who meet clinical, biochemical and neurologic criteria for moderate to severe NE:

Biochemical: Cord gas or blood gas within first hour of life with pH ≤7.00 or base deficit (BD) ≥16 mEq/L OR

Acute perinatal event (e.g., abruptio placenta, cord prolapse, uterine rupture, severe FHR abnormality such as variable or late decelerations) AND Requirement for positive pressure ventilation for apnea or poor respiratory effort since birth for at least 10 minutes OR 10 minute Apgar score ≤5

AND

Neurologic:

Seizures OR modified Sarnat score with abnormalities in at least 3 of the 6 categories; at least one must be altered level of consciousness (lethargy or stupor/coma) as determined by a certified examiner (All infants who meet criteria for potential inclusion will undergo standard neurologic exam as for infants ≥36 wks GA being considered for hypothermia, with findings recorded)

Exclusion criteria

Exclusion Criteria:

  • Receipt of sedative, analgesic or paralytic agent that may confound the qualifying neurologic exam
  • Etiology of NE not likely to be hypoxic-ischemic in origin
  • Major congenital anomaly that may confound outcome
  • Considered to be moribund and will not be receiving full intensive care
  • Equipment and/or appropriate staff not available
  • Core temperature \< 33.5oC for more than one hour at time of screening
  • Unable to randomize by 6 hours of age
  • Infant needs ECMO
  • All blood gases (cord and postnatal at \< 1hr of age) have a pH > 7.15 AND a base deficit \< 10mEq/L
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
168 participants (actual)

Study arms

  • Experimental
    Whole-body Hypothermia

    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours

    Device: Hypothermia

  • Placebo comparator
    Normothermia

    Control group (with esophageal temperature at or near 37.0°C) for 72 hours

    Procedure: Normothermic Control

Interventions

  • DeviceHypothermia

    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours

  • ProcedureNormothermic Control

    Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

06

What researchers measure

Primary outcomes

  1. Death or Moderate or Severe Disability

    Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Function (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to following commands/communicate. Moderate disability was defined as a Bayley III cognitive score between 70-84 and either a GMF level of 2 or a seizure disorder or a hearing deficit.

    Time frame: Birth to 18-22 months corrected age

Secondary outcomes

  1. Number of Deaths in the NICU and Following Discharge

    Number of deaths in the NICU and following discharge among infants with a primary outcome.

    Time frame: Birth to 18-22 months corrected age

  2. Number of Infants With Abnormal MRIs During Post-intervention Period

    An MRI was considered abnormal if any abnormal findings were indicated on the CRF form.

    Time frame: Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days

  3. Number of Infants With Moderate or Severe Disability

    Number of infants with moderate or severe disability among survivors through 18-22 months corrected age.

    Time frame: Birth to 18-22 months corrrected age

  4. Causes of Death

    Causes of any deaths that occurred through 18-22 months corrected age.

    Time frame: Birth to 18-22 months corrrected age

  5. Neurological Injury by Cranial Ultrasound During Intervention

    Infants with recorded events of intraventricular hemorrhage grade I, II, III, or IV, posterior fossa hemorrhage with/without shift of midline structures, intraparenchymal hemorrhage.

    Time frame: Within 6 hours of life to 72 hours after start of intervention

07

Results

Posted Apr 22, 2024

Participant flow

Participant flow — Overall Study
MilestoneWhole-body HypothermiaNormothermia
Started8880
Completed8571
Not completed39
Withdrew: Lost to follow-up37
Withdrew: Withdrawal by subject02

Outcome measures

PrimaryDeath or Moderate or Severe Disability

Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Function (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to following commands/communicate. Moderate disability was defined as a Bayley III cognitive score between 70-84 and either a GMF level of 2 or a seizure disorder or a hearing deficit.

Time frame:
Birth to 18-22 months corrected age
Reported as:
Count of participants · Participants
Death or Moderate or Severe Disability
ParticipantsWhole-body HypothermiaNormothermia
Death or Moderate or Severe Disability2920
Statistical analysis
  • Whole-body Hypothermia vs Normothermia · Risk ratio (rr): 1.11 · 95% CI 0.74 to 2.00The relative risk estimate was calculated by dividing risk under hypothermia by risk under normothermia.
SecondaryNumber of Deaths in the NICU and Following Discharge

Number of deaths in the NICU and following discharge among infants with a primary outcome.

Time frame:
Birth to 18-22 months corrected age
Reported as:
Count of participants · Participants
Number of Deaths in the NICU and Following Discharge
ParticipantsWhole-body HypothermiaNormothermia
Number of Deaths in the NICU and Following Discharge189
SecondaryNumber of Infants With Abnormal MRIs During Post-intervention Period

An MRI was considered abnormal if any abnormal findings were indicated on the CRF form.

Time frame:
Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days
Reported as:
Count of participants · Participants
Number of Infants With Abnormal MRIs During Post-intervention Period
ParticipantsWhole-body HypothermiaNormothermia
Number of Infants With Abnormal MRIs During Post-intervention Period4850
SecondaryNumber of Infants With Moderate or Severe Disability

Number of infants with moderate or severe disability among survivors through 18-22 months corrected age.

Time frame:
Birth to 18-22 months corrrected age
Reported as:
Count of participants · Participants
Number of Infants With Moderate or Severe Disability
ParticipantsWhole-body HypothermiaNormothermia
Number of Infants With Moderate or Severe Disability1111
SecondaryCauses of Death

Causes of any deaths that occurred through 18-22 months corrected age.

Time frame:
Birth to 18-22 months corrrected age
Reported as:
Count of participants · Participants
Causes of Death
ParticipantsWhole-body HypothermiaNormothermia
Asphyxial Brain Injury144
Multi-organ Failure22
Cardiomyopathy10
Complications of HIE10
BPD/CLD01
Secondary to severe HIE01
Pulmonary Hypoplasia01
SecondaryNeurological Injury by Cranial Ultrasound During Intervention

Infants with recorded events of intraventricular hemorrhage grade I, II, III, or IV, posterior fossa hemorrhage with/without shift of midline structures, intraparenchymal hemorrhage.

Time frame:
Within 6 hours of life to 72 hours after start of intervention
Reported as:
Count of participants · Participants
Neurological Injury by Cranial Ultrasound During Intervention
ParticipantsWhole-body HypothermiaNormothermia
Neurological Injury by Cranial Ultrasound During Intervention23

Adverse events

Collected over SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Whole-body Hypothermia18/88 (20.5%)29/88 (33%)22/88 (25%)
Normothermia9/80 (11.3%)17/78 (21.8%)12/78 (15.4%)
Most frequent serious events
Showing 10 of 33
Most frequent serious events
EventWhole-body HypothermiaNormothermia
ThrombocytopeniaBlood and lymphatic system disorders6/889/78
Persistent metabolic acidosisMetabolism and nutrition disorders3/885/78
HyperglycemiaMetabolism and nutrition disorders5/882/78
Intracranial bleedingNervous system disorders4/884/78
Major BleedingVascular disorders1/884/78
PPHNCongenital, familial and genetic disorders4/884/78
HypoglycemiaMetabolism and nutrition disorders0/882/78
HIENervous system disorders1/882/78
Asphyxial Brain InjuryNervous system disorders2/880/78
ThrombosisVascular disorders0/881/78
Most frequent other events
Most frequent other events
EventWhole-body HypothermiaNormothermia
HyperglycemiaMetabolism and nutrition disorders15/888/78
ThrombocytopeniaBlood and lymphatic system disorders6/883/78
ErythemaSkin and subcutaneous tissue disorders4/881/78
HypoglycemiaMetabolism and nutrition disorders1/883/78
Arrhythmia needing treatmentCardiac disorders0/881/78
Bilateral mIneralizing vasculopathyVascular disorders0/881/78
Persistent metabolic acidosisMetabolism and nutrition disorders1/880/78
Intracranial bleedingNervous system disorders1/880/78
PPHNCongenital, familial and genetic disorders1/880/78

Baseline characteristics

Age, Continuous
Age, Continuous(Hours)Whole-body HypothermiaNormothermiaTotal
Mean4.5 ± 1.24.5 ± 1.34.5 ± 1.3
Sex: Female, Male
Sex: Female, Male(Participants)Whole-body HypothermiaNormothermiaTotal
Female423577
Male464591
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Whole-body HypothermiaNormothermiaTotal
Hispanic or Latino151025
Not Hispanic or Latino7167138
Unknown or Not Reported235
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Whole-body HypothermiaNormothermiaTotal
American Indian or Alaska Native101
Asian549
Native Hawaiian or Other Pacific Islander000
Black or African American273158
White524294
More than one race000
Unknown or Not Reported336
Region of Enrollment
Region of Enrollment(participants)Whole-body HypothermiaNormothermiaTotal
United States8880168
Level of Encephalopathy
Level of Encephalopathy(Participants)Whole-body HypothermiaNormothermiaTotal
Moderate6157118
Severe272350
Birthweight
Birthweight(grams)Whole-body HypothermiaNormothermiaTotal
Mean2463.5 ± 634.32371.4 ± 607.92419.6 ± 621.7
Length
Length(cm)Whole-body HypothermiaNormothermiaTotal
Mean46.0 ± 3.245.1 ± 2.845.6 ± 3.1

1 further baseline measures are reported on the registry.

08

Study locations

18 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35233, United States
  • Stanford University
    Palo Alto, California 94304, United States
  • Emory University
    Atlanta, Georgia 30303, United States
  • Indiana University
    Indianapolis, Indiana 46202, United States
  • University of Iowa
    Iowa City, Iowa 52242, United States
  • Wayne State University
    Detroit, Michigan 48201, United States
  • University of New Mexico
    Albuquerque, New Mexico 87131, United States
  • University of Rochester
    Rochester, New York 14642, United States
  • RTI International
    Durham, North Carolina 27705, United States
  • Duke University
    Durham, North Carolina 27710, United States
  • Cincinnati Children's Medical Center
    Cincinnati, Ohio 45267, United States
  • Case Western Reserve University, Rainbow Babies and Children's Hospital
    Cleveland, Ohio 44106, United States
  • Research Institute at Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • Univeristy of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Brown University, Women & Infants Hospital of Rhode Island
    Providence, Rhode Island 02905, United States
  • University of Texas Southwestern Medical Center at Dallas
    Dallas, Texas 75235, United States
  • University of Texas Health Science Center at Houston
    Houston, Texas 77030, United States
  • University of Utah
    Salt Lake City, Utah 84108, United States
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov)

10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of May 2015, a primary completion of Dec 2022 and a completion of Dec 2022. It does not say whether these dates are actual or estimated.

Results were first posted in Apr 2024, 1 year 4 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 13, 2013
First posted
Feb 15, 2013
Start
May 2015
Primary completionActual
Dec 9, 2022
CompletionActual
Dec 9, 2022
Results first posted
Apr 22, 2024
Last update
Nov 4, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 4, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01793129
Lead sponsor
NICHD Neonatal Research Network
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Sponsor
First posted
Feb 15, 2013
Start date
May 2015
Primary completion
Dec 9, 2022
Completion
Dec 9, 2022
Results posted
Apr 22, 2024
Last update
Nov 4, 2024

Study contacts

Michele C Walsh, MD
principal investigator · Case Western Reserve University, Rainbow Babies and Children's Hospital
Seetha Shankaran, MD
principal investigator · Wayne State University
Abbot R Laptook, MD
principal investigator · Brown University, Women & Infants Hospital of Rhode Island
C. Michael Cotten, MD
principal investigator · Duke University
David P Carlton, MD
principal investigator · Emory University
Greg Sokol, MD, MS
principal investigator · Indiana University
Abhik Das, PhD
principal investigator · RTI International
Krisa P Van Meurs, MD
principal investigator · Stanford University
Brenda Poindexter, MD
principal investigator · Children's Hospital Medical Center, Cincinnati
Wally A Carlo, MD
principal investigator · University of Alabama at Birmingham
Edward F Bell, MD
principal investigator · University of Iowa
Kristi L Watterberg, MD
principal investigator · University of New Mexico
Myra Wyckoff, MD
principal investigator · University of Texas Southwestern Medical Center at Dalla
Jon E Tyson, MD, MPH
principal investigator · The University of Texas Health Science Center, Houston
Eric Eichenwald, MD
principal investigator · University of Pennsylvania
Carl T D'Angio, MD
principal investigator · University of Rochester
Pablo Sanchez, MD
principal investigator · Research Institute at Nationwide Children's Hospital
Bradley Yoder, MD
principal investigator · University of Utah

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.

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NICHD Neonatal Research Network

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