Late Hypothermia for Hypoxic-Ischemic Encephalopathy

NCT00614744 | Completed Results DMC

• 26 other identifiers: NICHD-NRN-0038U10HD036790U10HD021364U10HD021373U10HD021385U10HD027851U10HD027853U10HD027856U10HD027871U10HD027880U10HD027904U10HD034216U10HD040492U10HD040689U10HD053089U10HD053109U10HD053119U10HD053124UL1RR024139UL1RR025744UL1RR024979U10HD0682441U10HD068263-01U10HD068270U10HD068278U10HD068284
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 22

Brief 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 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.

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 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.

  Birth to 18-22 months corrected gestational age

Secondary Outcomes (9)

• Number of Deaths in the NICU and Following Discharge

  Birth to 18-22 months corrected gestational age

• Number of Infants With Moderate and Severe Disability

  Birth to 18-22 months corrected gestational age

• Number of Infants With Mild, Moderate and Severe Disability

  Birth to 18-22 months corrected gestational age

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

  Birth to 18-22 months corrected gestational age

• Number of Infants With Non-CNS Organ System Dysfunction

  Birth to 18-22 months corrected gestational age

Study Arms (2)

Whole-body Hypothermia

EXPERIMENTAL

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

Procedure: Hypothermia

Normothermia

ACTIVE COMPARATOR

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

Procedure: Normothermic Control

Interventions

Hypothermia PROCEDURE

Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 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: 6 Hours - 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (22)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Los Angeles

Los Angeles, California, 90025, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06504, 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

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, 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 (3)

• 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.

  PMID: 35835616 DERIVED

• 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.

  PMID: 33189747 DERIVED

• 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.

  PMID: 29067428 DERIVED

Related Links

• NICHD Neonatal Research Network

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: Abbot Laptook
• Organization: Brown University, Women & Infants Hospital of Rhode Island

alaptook@wihri.org

401-274-1122

Study Officials

• Abbot R. Laptook, MD

  Brown University, Women & Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

• Michele C. Walsh, MD MS

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

  PRINCIPAL INVESTIGATOR

• Ronald N. Goldberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Barbara J. Stoll, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Brenda B. Poindexter, MD MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Abhik Das, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Krisa P. Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Ivan D. Frantz III, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

• Kurt Schibler, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Waldemar 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 Dallas

  PRINCIPAL INVESTIGATOR

• Kathleen A. Kennedy, MD MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Roger G. Faix, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

• Seetha Shankaran, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Richard A. Ehrenkranz, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• William Truog, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

• Barbara Schmidt, MD, MSc

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Carl D'Angio, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Uday Devaskar, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Pablo Sanchez, M.D

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 11, 2008
• First Posted: February 13, 2008
• Study Start: April 1, 2008
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: March 9, 2021
• Results First Posted: August 7, 2017

Record last verified: 2021-02

Locations

US (22)