Late Hypothermia for Hypoxic-Ischemic Encephalopathy - Full Text View

Purpose

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 18-24 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.

Condition	Intervention	Phase
Infant, Newborn Hypoxia, Brain Hypoxia-Ischemia, Brain Encephalopathy, Hypoxic-Ischemic Hypoxic-Ischemic Encephalopathy Ischemic-Hypoxic Encephalopathy	Procedure: Hypothermia Procedure: Normothermic Control	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hypothermia

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Death or moderate or severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number of deaths in the NICU and following discharge [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with moderate and severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with mild, moderate and severe disability [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with any disability based on level of encephalopathy at randomization [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with non-CNS organ system dysfunction [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with a DNR order [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with a DNR order and support is withdrawn [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with a DNR order and either die or survive [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]
Number of infants with neonatal seizures, with and without EEG abnormalities [ Time Frame: Birth to 18-24 months corrected gestational age ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	168
Study Start Date:	April 2008
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Procedure: Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours
Active Comparator: Normothermia Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours	Procedure: Normothermic Control Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

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.

Eligibility

Ages Eligible for Study:	up to 24 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

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).

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614744

Contacts

Contact: Abbot R. Laptook, MD	(401) 274-1122	alaptook@WIHRI.org
Contact: Rosemary D. Higgins, MD	(301) 496-5575	higginsr@mail.nih.gov

Hide Study Locations

Locations

United States, Alabama
University of Alabama at Birmingham	Recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD 205-934-4680 wcarlo@peds.uab.edu
Contact: Monica V. Collins, RN BSN (205) 934-5771 mcollins@peds.uab.edu
Principal Investigator: Waldemar A. Carlo, MD
Sub-Investigator: Robert L. Schelonka, MD
United States, California
University of California - Los Angeles	Recruiting
Los Angeles, California, United States, 90025
Contact: Uday Devaskar, MD 310-825-9357 udevaskar@mednet.ucla.edu
Contact: Teresa Chanlaw, BS (310) 794-4972 tchanlaw@mednet.ucla.edu
Principal Investigator: Uday Devaskar, MD
Stanford University	Recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD 650-723-5711 vanmeurs@leland.stanford.edu
Contact: M. Bethany Ball, BS CCRC (650) 725-8342 mbball@stanford.edu
Principal Investigator: Krisa P. Van Meurs, MD
Principal Investigator: David K. Stevenson, MD
United States, Connecticut
Yale University	Active, not recruiting
New Haven, Connecticut, United States, 06504
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30303
Contact: Barbara J. Stoll, MD 404-727-5740 barbara_stoll@oz.ped.emory.edu
Contact: Ellen Hale, RN BS (404) 616-4218 ellen_hale@oz.ped.emory.edu
Principal Investigator: Barbara J. Stoll, MD
United States, Indiana
Indiana University	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Brenda B. Poindexter, MD MS 317-274-3592 bpoindex@iupui.edu
Contact: Leslie D. Wilson, RN BSN (317) 274-8255 ldw@iupui.edu
Principal Investigator: Brenda B. Poindexter, MD MS
United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F. Bell, MD 319-356-4006 edward-bell@uiowa.edu
Contact: Karen J. Johnson, RN BSN (319) 356-2924 karen-johnson@uiowa.edu
Principal Investigator: Edward F. Bell, MD
United States, Massachusetts
Tufts Medical Center	Active, not recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
Wayne State University	Recruiting
Detroit, Michigan, United States, 48201
Contact: Seetha Shankaran, MD 313-580-4452 sshankar@med.wayne.edu
Contact: Rebecca Bara, RN BSN (313) 745-1436 rbara@med.wayne.edu
Principal Investigator: Seetha Shankaran, MD
United States, Missouri
Children's Mercy Hospital	Recruiting
Kansas City, Missouri, United States, 64108
Contact: William Truog, MD 816-234-3592 wtruog@cmh.edu
Contact: Cheri Gauldin, BSN (816) 234-3920 cagauldin@cmh.edu
Principal Investigator: William Truog, MD
United States, New Mexico
University of New Mexico	Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L. Watterberg, MD 505-272-3967 kwatterberg@salud.unm.edu
Contact: Conra Backstrom Lacy, RN (505) 272-0367 cbackstrom@salud.unm.edu
Principal Investigator: Kristi L. Watterberg, MD
United States, New York
University of Rochester	Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD 585-273-4911 carl_dangio@urmc.rochester.edu
Principal Investigator: Carl T D'Angio, MD
United States, North Carolina
RTI International	Active, not recruiting
Durham, North Carolina, United States, 27705
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Ronald N. Goldberg, MD 919-681-6025 goldb008@mc.duke.edu
Contact: Katherine A. Foy (919) 668-3360 foy00004@mc.duke.edu
Principal Investigator: Ronald N. Goldberg, MD
United States, Ohio
Cincinnati Children's Medical Center	Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Kurt Schibler, MD 513-636-3972 kurt.schibler@cchmc.org
Contact: Cathy Grisby, BSN CCRC (513) 558-4953 grisbyca@email.uc.edu
Principal Investigator: Kurt Schibler, MD
Case Western Reserve University, Rainbow Babies and Children's Hospital	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD MS 216-844-3759 mcw3@cwru.edu
Contact: Nancy S. Newman, BA RN (216) 368-3084 nxs5@cwru.edu
Principal Investigator: Michele C. Walsh, MD MS
Research Institute at Nationwide Children's Hospital	Recruiting
Columbus, Ohio, United States, 43205
Contact: Leif Nelin, MD 614-722-3030 Leif.Nelin@nationwidechildrens.org
Contact: Christine Fortney, MS, RN 614-722-6489 christine.fortney@nationwidechildrens.org
Principal Investigator: Leif Nelin, MD
United States, Pennsylvania
Univeristy of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara Schmidt, MD 215-662-3228 barbara.schmidt@uphs.upenn.edu
Contact: Aasma Chaudhary, BS 215-615-5442 aasma.chaudhary@uphs.upenn.edu
Principal Investigator: Barbara Schmidt, MD
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island	Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD 401-274-1122 alaptook@WIHRI.org
Contact: Angelita Hensman (401) 274-1122 ahensman@wihri.org
Principal Investigator: Abbot R. Laptook, MD
Sub-Investigator: William Oh, MD
United States, Texas
University of Texas Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75235
Contact: Pablo J. Sanchez, MD 214-648-3753 Pablo.Sanchez@UTSouthwestern.edu
Contact: Diana M. Vasil, RNC-NIC (214) 648-3789 Diana.Vasil@utsouthwestern.edu
Principal Investigator: Pablo J. Sanchez, MD
University of Texas Health Science Center at Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Kathleen A. Kennedy, MD MPH 713-500-6708 Kathleen.A.Kennedy@uth.tmc.edu
Contact: Georgia E. McDavid, RN (713) 500-5734 Georgia.E.McDavid@uth.tmc.edu
Principal Investigator: Kathleen A. Kennedy, MD MPH
Principal Investigator: Jon E. Tyson, MD MPH
United States, Utah
University of Utah	Active, not recruiting
Salt Lake City, Utah, United States, 84108

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Center for Research Resources (NCRR)

Investigators

Principal Investigator:	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	Cincinnati Children's Medical Center
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:	Pablo J. Sanchez, 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, MO
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:	Leif Nelin	Ohio State University

More Information

Additional Information:

NICHD Neonatal Research Network This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00614744 History of Changes
Other Study ID Numbers:	NICHD-NRN-0038, U10HD036790, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, UL1RR024139, UL1RR025744, UL1RR024979, U10HD068244, 1U10HD068263-01, U10HD068270, U10HD068278, U10HD068284
Study First Received:	February 11, 2008
Last Updated:	January 17, 2013
Health Authority:	United States: Federal Government United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

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

Additional relevant MeSH terms:

Hypoxia, Brain
Brain Ischemia
Hypothermia
Ischemia
Brain Damage, Chronic
Delirium
Encephalitis
Hepatic Encephalopathy
Neurotoxicity Syndromes
Anoxia
Hypoxia-Ischemia, Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebrovascular Disorders

Vascular Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Liver Failure
Hepatic Insufficiency

ClinicalTrials.gov processed this record on May 23, 2013