Preemie Hypothermia for Neonatal Encephalopathy

NCT01793129 | Completed Results DMC FDA Device

• 21 other identifiers: NICHD-NRN-0051U10HD021364U10HD040689U10HD021385U10HD027851U10HD027853U10HD027856U10HD027904U10HD027880U10HD034216U10HD021373U10HD040492U10HD053109U10HD040461U10HD068244U10HD068263U10HD068270U10HD068278U10HD068284U10HD036790UG1HD087226
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 18

Brief 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.

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

Outcome Measures

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.

  Birth to 18-22 months corrected age

Secondary Outcomes (5)

• Number of Deaths in the NICU and Following Discharge

  Birth to 18-22 months corrected age

• Number of Infants With Abnormal MRIs During Post-intervention Period

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

• Number of Infants With Moderate or Severe Disability

  Birth to 18-22 months corrrected age

• Causes of Death

  Birth to 18-22 months corrrected age

• Neurological Injury by Cranial Ultrasound During Intervention

  Within 6 hours of life to 72 hours after start of intervention

Study Arms (2)

Whole-body Hypothermia

EXPERIMENTAL

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

Device: Hypothermia

Normothermia

PLACEBO COMPARATOR

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

Procedure: Normothermic Control

Interventions

Hypothermia DEVICE

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

Whole-body Hypothermia

Normothermic Control PROCEDURE

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

Normothermia

Eligibility Criteria

• Age: 33 Weeks - 35 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• 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.

  PMID: 39992674 DERIVED

Related Links

• Neonatal Research Network website

MeSH Terms

Conditions

Hypoxia, Brain; Hypoxia-Ischemia, Brain; Hypothermia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Ischemia; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Body Temperature Changes

Results Point of Contact

• Title: Dr. Abhik Das
• Organization: RTI International

adas@rti.org

301-770-8214

Study Officials

• Michele C Walsh, MD

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

  PRINCIPAL INVESTIGATOR

• Seetha Shankaran, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Abbot R Laptook, MD

  Brown University, Women & Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

• C. Michael Cotten, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• David P Carlton, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Greg Sokol, MD, MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Abhik Das, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Krisa P Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Brenda Poindexter, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Wally A Carlo, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Edward F Bell, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Kristi L Watterberg, MD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

• Myra Wyckoff, MD

  University of Texas Southwestern Medical Center at Dalla

  PRINCIPAL INVESTIGATOR

• Jon E Tyson, MD, MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Eric Eichenwald, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Carl T D'Angio, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Pablo Sanchez, MD

  Research Institute at Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Bradley Yoder, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 15, 2013
• Study Start: May 1, 2015
• Primary Completion: December 9, 2022
• Study Completion: December 9, 2022
• Last Updated: November 4, 2024
• Results First Posted: April 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (18)