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Infant, NewbornNCT00614744

Late Hypothermia for Hypoxic-Ischemic Encephalopathy

A study testing Hypothermia in people with Infant, Newborn and Hypoxia, Brain, run by NICHD Neonatal Research Network at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is a randomized, placebo-controlled, clinical trial to evaluate whether induced whole-body hypothermia initiated between 6-24 hours of age and continued for 96 hours in infants ≥ 36 weeks gestational age with hypoxic-ischemic encephalopathy will reduce the incidence of death or disability at 18-22 months of… Read more about this study

Who is it for?
Ages 6 to 24 hours
What is being tested?
Hypothermia
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
22 sitesUnited States
Study dates
Apr 2008to Jun 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 6 to 24 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Infants born at 36 0/7ths weeks gestational age or greater (by best obstetrical estimate)
  • Postnatal age between 6 and 24 hours following birth
  • Infants with a high probability of acute hemodynamic compromise, such as those with:
  • An acute perinatal event (abruptio placenta, cord prolapse, severe FHR abnormality)
  • An Apgar score ≤ 5 at 10 minutes
  • Continued need for ventilation initiated at birth for at least 10 minutes
Show all 11Show fewer
  • Cord pH or first postnatal blood gas pH at ≤ 1 hour of ≤ 7.0
  • Base deficit on cord gas or first postnatal blood gas at ≤ 1 hour of ≥ 16 mEq/L
  • Infants matching the above criteria who also have an abnormal neurological exam showing the presence of moderate or severe encephalopathy
  • Infants whose parents/legal guardians have provided consent for enrollment.
  • NOTE: These inclusion criteria are identical to the NICHD Neonatal Research Network's 2005 Hypothermia study (see links below), except for the time of entry (6-24 hours vs. < 6 hours of age).

Who cannot join

  • Any infant with a core body temperature (axilla, rectal) less than 34.0°C for greater than 1 hour
  • Presence of a known anomaly or chromosomal aberration
  • Birth weight < 1,800 grams
  • Infant in extremis
  • Infants whose parents/legal guardians or attending physician refuse consent

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites
  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Emory University

    Atlanta, Georgia, 30303

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • 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

  • Yale University

    New Haven, Connecticut, 06504

  • 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

  • University of Utah

    Salt Lake City, Utah, 84108

Other trials in United States

About this study

Official title: Evaluation of Systemic Hypothermia Initiated After 6 Hours of Age in Infants ≥36 Weeks Gestation With Hypoxic-Ischemic Encephalopathy: A Bayesian Evaluation. A Protocol for the NICHD Neonatal Research Network

This study is a randomized, placebo-controlled, clinical trial to evaluate whether induced whole-body hypothermia initiated between 6-24 hours of age and continued for 96 hours in infants ≥ 36 weeks gestational age with hypoxic-ischemic encephalopathy will reduce the incidence of death or disability at 18-22 months of age. The study will enroll 168 infants with signs of hypoxic-ischemic encephalopathy at 16 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

Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by acute or subacute brain injury due to asphyxia. In most cases the underlying cause and timing of injury are unknown, but many cases are 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.

The incidence of long-term complications depends on the severity of HIE. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term neurological disabilities - mental retardation, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.

Because animal data suggests that brain injury from HIE evolves over several hours to days after the initial asphyxic insult, induced hypothermia holds promise as a neuroprotective therapy. Additional trials are needed to help define the most effective cooling strategies.

With this in mind, and knowing that many babies with HIE arrive at neonatal intensive care units several hours after birth, this study will evaluate the safety and efficacy of initiating hypothermia 6-24 hours after birth.

Study subjects: Infants born at 36 0/7ths weeks or greater gestational age that have been diagnosed with neonatal depression, perinatal asphyxia, or encephalopathy. The goal is to enroll 168 subjects.

Stratification: After informed consent is obtained, infants will be randomized to either a hypothermia arm (with a target esophageal temperature of 33.5°C) or a control arm (37.0°C) for 96 hours. Enrolled infants will be stratified by age of enrollment (≤ 12 and > 12 hours) and stage of encephalopathy (moderate or severe).

Informed Consent: Parents of eligible infants will be approached for consent to enroll in the study if the infant has a high probability of acute hemodynamic compromise, as defined above. Subsequent screening will determine whether the infant meets all inclusion criteria.

Randomization: eligible and consented infants will be randomly assigned to either a hypothermia intervention group, or a non-cooled (control) group.

Study Intervention: Induced whole-body hypothermia (with a target esophageal temperature of 33.5°C) or a control group (37.0°C) for 96 hours.

Interim Study Interruptions: None to date.

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

Being tested
Hypothermia, Normothermic Control
Keywords
NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia
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.

  • HypothermiaProcedure or surgery

    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours

  • Normothermic ControlProcedure or surgery

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

Study groups in NCT00614744
Study groupRoleWhat they receive
Whole-body HypothermiaExperimentalInduced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Receives: Procedure: Hypothermia
NormothermiaActive comparatorNormothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Receives: Procedure: Normothermic Control

What is being measured

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

  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 Functional (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to follow 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.

    Measured: Birth to 18-22 months corrected gestational age

Secondary outcomes (9)
  1. Number of Deaths in the NICU and Following Discharge

    Measured: Birth to 18-22 months corrected gestational age

  2. Number of Infants With Moderate and Severe Disability

    Moderate disability will be 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 or Gross Motor Functional (GMF) Level of 3-5 or blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

    Measured: Birth to 18-22 months corrected gestational age

  3. Number of Infants With Mild, Moderate and Severe Disability

    Mild disability will be defined by either a Bayley III cognitive score of 70-84 alone or a Bayley III cognitive score >= 85 and any of the following: presence of a GMF level 1 or 2 OR seizure disorder or hearing loss. 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 OR Gross Motor Functional (GMF) Level of 3-5 OR blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

    Measured: Birth to 18-22 months corrected gestational age

  4. Number of Infants With Any Disability Based on Level of Encephalopathy at Randomization

    Mild disability will be defined by either a Bayley III cognitive score of 70-84 alone or a Bayley III cognitive score >= 85 and any of the following: presence of a GMF level 1 or 2OR seizure disorder or hearing loss. 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 OR Gross Motor Functional (GMF) Level of 3-5 OR blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

    Measured: Birth to 18-22 months corrected gestational age

  5. Number of Infants With Non-CNS Organ System Dysfunction

    Based on observing presence of organ dysfunction on at least one of the following: Pulmonary (Meconium aspiration syndrome, PPHN, Pulmonary hemorrhage, Pneumonia, Chronic lung disease, ECMO, INO), Cardiovascular (Cardiomegaly, Cardiac failure, Cardiac dysfunction (by echo), Cardiac ischemia (by EKG and/or increased enzymes), Hypotension, Arrhythmia), Renal (Oliguria, Anuria, Dialysis), Gastrointestinal (NEC, Hepatic dysfunction), Hematologic (DIC) and Metabolic (Hypoglycemia, Hypocalcemia, Hypomagnesemia)

    Measured: Birth to 18-22 months corrected gestational age

  6. Number of Infants With a DNR Order

    Measured: Birth to 18-22 months corrected gestational age

  7. Number of Infants With a DNR Order and Support is Withdrawn

    Measured: Birth to 18-22 months corrected gestational age

  8. Number of Infants With a DNR Order That Died

    Measured: Birth to 18-22 months corrected gestational age

  9. Number of Infants With Neonatal Seizures, With and Without EEG Abnormalities

    Measured: Birth to 18-22 months corrected gestational age

Timeline

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

  1. First posted13 Feb 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionJun 2016
  4. Study completionJun 2016

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00614744
Sponsor's protocol ID
NICHD-NRN-0038
Other IDs
U10HD036790, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871
Status last verified
Feb 2021
First submitted
11 Feb 2008
Last updated
9 Mar 2021
Data monitoring committee
Yes

Publications

  • 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
  • Laptook AR, Shankaran S, Barnes P, Rollins N, Do BT, Parikh NA, Hamrick S, Hintz SR, Tyson JE, Bell EF, Ambalavanan N, Goldberg RN, Pappas A, Huitema C, Pedroza C, Chaudhary AS, Hensman AM, Das A, Wyckoff M, Khan A, Walsh MC, Watterberg KL, Faix R, Truog W, Guillet R, Sokol GM, Poindexter BB, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial. J Pediatr. 2021 Mar;230:106-111.e6. doi: 10.1016/j.jpeds.2020.11.015. Epub 2020 Nov 13.

    PubMed 33189747
  • Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, Parikh NA, Ambalavanan N, Pedroza C, Pappas A, Das A, Chaudhary AS, Ehrenkranz RA, Hensman AM, Van Meurs KP, Chalak LF, Khan AM, Hamrick SEG, Sokol GM, Walsh MC, Poindexter BB, Faix RG, Watterberg KL, Frantz ID 3rd, Guillet R, Devaskar U, Truog WE, Chock VY, Wyckoff MH, McGowan EC, Carlton DP, Harmon HM, Brumbaugh JE, Cotten CM, Sanchez PJ, Hibbs AM, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017 Oct 24;318(16):1550-1560. doi: 10.1001/jama.2017.14972.

    PubMed 29067428

Questions about this trial

What is this clinical trial studying?

A study testing Hypothermia in people with Infant, Newborn and Hypoxia, Brain, run by NICHD Neonatal Research Network at 22 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 11 inclusion and 5 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: finished, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 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 7 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 or Severe Disability (time frame: Birth to 18-22 months corrected gestational 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 NCT00614744, which also lists 3 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 9 Mar 2021.

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