Infant, NewbornNCT01793129
Preemie Hypothermia for Neonatal Encephalopathy
A study testing Hypothermia in people with Infant, Newborn and Hypoxia, Brain, run by NICHD Neonatal Research Network at 18 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 33 to 35 weeks
- Conditions the study is for
- Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain
- What is being tested?
- Hypothermia
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 18 sitesUnited States
- Study dates
- May 2015to 9 Dec 2022
- Phase
- Interventional
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 33 to 35 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 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
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
About this study
Official title: A Randomized Trial of Targeted Temperature Management With Whole Body Hypothermia For Moderate And Severe Hypoxic-Ischemic Encephalopathy In Premature Infants 33-35 Weeks Gestational Age.
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.
- Conditions
- Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain, Encephalopathy, Hypoxic-Ischemic, Hypoxic-Ischemic Encephalopathy, Ischemic-Hypoxic Encephalopathy
- 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.
HypothermiaDevice
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours
Normothermic ControlProcedure or surgery
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
| Study group | Role | What they receive |
|---|---|---|
| Whole-body Hypothermia | Experimental | Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Receives: Device: Hypothermia |
| Normothermia | Placebo comparator | Control group (with esophageal temperature at or near 37.0°C) for 72 hours Receives: Procedure: Normothermic Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Birth to 18-22 months corrected age
Secondary outcomes (5)
Number of Deaths in the NICU and Following Discharge
Number of deaths in the NICU and following discharge among infants with a primary outcome.
Measured: Birth to 18-22 months corrected age
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.
Measured: Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days
Number of Infants With Moderate or Severe Disability
Number of infants with moderate or severe disability among survivors through 18-22 months corrected age.
Measured: Birth to 18-22 months corrrected age
Causes of Death
Causes of any deaths that occurred through 18-22 months corrected age.
Measured: Birth to 18-22 months corrrected age
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.
Measured: Within 6 hours of life to 72 hours after start of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startMay 2015
- Primary completion9 Dec 2022
- Study completion9 Dec 2022
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 (1)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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Michele C Walsh, MD, Principal investigator, Case Western Reserve University, Rainbow Babies and Children's HospitalSeetha Shankaran, MD, Principal investigator, Wayne State UniversityAbbot R Laptook, MD, Principal investigator, Brown University, Women & Infants Hospital of Rhode IslandC. Michael Cotten, MD, Principal investigator, Duke UniversityDavid P Carlton, MD, Principal investigator, Emory UniversityGreg Sokol, MD, MS, Principal investigator, Indiana UniversityAbhik Das, PhD, Principal investigator, RTI InternationalKrisa P Van Meurs, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01793129
- Sponsor's protocol ID
- NICHD-NRN-0051
- Other IDs
- U10HD021364, U10HD040689, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027904, U10HD027880
- Status last verified
- Oct 2024
- First submitted
- 13 Feb 2013
- Last updated
- 4 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- 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)
Publications
Faix RG, Laptook AR, Shankaran S, Eggleston B, Chowdhury D, Heyne RJ, Das A, Pedroza C, Tyson JE, Wusthoff C, Bonifacio SL, Sanchez PJ, Yoder BA, Laughon MM, Vasil DM, Van Meurs KP, Crawford MM, Higgins RD, Poindexter BB, Colaizy TT, Hamrick SEG, Chalak LF, Ohls RK, Hartley-McAndrew ME, Dysart K, D'Angio CT, Guillet R, Kicklighter SD, Carlo WA, Sokol GM, DeMauro SB, Hibbs AM, Cotten CM, Merhar SL, Bapat RV, Harmon HM, Sewell E, Winter S, Natarajan G, Mosquera R, Hintz SR, Maitre NL, Benninger KL, Peralta-Carcelen M, Hines AC, Duncan AF, Wilson-Costello DE, Trembath A, Malcolm WF, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks' Gestation: A Randomized Clinical Trial. JAMA Pediatr. 2025 Apr 1;179(4):396-406. doi: 10.1001/jamapediatrics.2024.6613.
PubMed 39992674