Preemie Hypothermia for Neonatal Encephalopathy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01793129
First received: February 13, 2013
Last updated: August 13, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Infant, Newborn
Hypoxia, Brain
Hypoxia-Ischemia, Brain
Encephalopathy, Hypoxic-Ischemic
Hypoxic-Ischemic Encephalopathy
Ischemic-Hypoxic Encephalopathy
Device: 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: 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.

Resource links provided by NLM:


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 18-22 months corrected age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of deaths in the NICU and following discharge [ Time Frame: Birth to 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Differences in MRI findings after cessation of cooling/control obtained [ Time Frame: Birth to 40 weeks corrected age ] [ Designated as safety issue: Yes ]
  • Number of infants with moderate and severe disability [ Time Frame: Birth to 18-22 months corrrected age ] [ Designated as safety issue: Yes ]
  • Causes of Death [ Time Frame: Birth to 18-22 months corrrected age ] [ Designated as safety issue: Yes ]
    withdrawal of support and reasons for such will be tracked; attempts will be made to obtain autopsy whenever possible

  • Neurological injury by cranial ultrasound within 24 hours of enrollment [ Time Frame: Birth to 2 days of life ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 168
Study Start Date: October 2014
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: August 2017 (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 72 hours
Device: Hypothermia
Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours
Placebo Comparator: Normothermia
Control group (with esophageal temperature at or near 37.0°C) for 72 hours
Procedure: Normothermic Control
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

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.

  Eligibility

Ages Eligible for Study:   33 Weeks to 35 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01793129

Contacts
Contact: Roger G Faix, MD 801-581-7052
Contact: Rosemary D Higgins, MD 301-435-5575

Locations
United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD    205-934-4680      
Principal Investigator: Waldemar A. Carlo, MD         
United States, California
University of California - Los Angeles Not yet recruiting
Los Angeles, California, United States, 90025
Contact: Uday Devaskar, MD    310-825-9314      
Principal Investigator: Uday Devaskar, MD         
Stanford University Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD    650-723-5711      
Principal Investigator: Krisa P. Van Meurs, MD         
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30303
Contact: Barbara J. Stoll, MD    404-727-2456      
Principal Investigator: Barbara J. Stoll, MD         
United States, Indiana
Indiana University Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Brenda B. Poindexter, MD MS    317-274-4768      
Principal Investigator: Brenda B. Poindexter, MD MS         
United States, Iowa
University of Iowa Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F. Bell, MD    319-356-4006      
Principal Investigator: Edward F. Bell, MD         
United States, Michigan
Wayne State University Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Seetha Shankaran, MD    313-745-1436      
Principal Investigator: Seetha Shankaran, MD         
United States, Missouri
Children's Mercy Hospital Not yet recruiting
Kansas City, Missouri, United States, 64108
Contact: William Truog, MD    816-234-3592      
Principal Investigator: William Truog, MD         
United States, New Mexico
University of New Mexico Not yet recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Kristi L. Watterberg, MD    505-272-8609      
Principal Investigator: Kristi L. Watterberg, MD         
United States, New York
University of Rochester Not yet recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD    585-273-4911      
Principal Investigator: Carl T D'Angio, MD         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Ronald N. Goldberg, MD    919-681-6024      
Principal Investigator: Ronald N. Goldberg, MD         
Sub-Investigator: C. Michael Cotten, MD MHS         
RTI International Not yet recruiting
Durham, North Carolina, United States, 27705
Contact: Abhik Das, PhD    301-230-4640      
Principal Investigator: Abhik Das, PhD         
United States, Ohio
Cincinnati Children's Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Kurt Schibler, MD    513-636-3972      
Principal Investigator: Kurt Schibler, MD         
Case Western Reserve University, Rainbow Babies and Children's Hospital Not yet recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD, MS    216-844-3387      
Contact: S.         
Principal Investigator: Michele C. Walsh, MD MS         
Research Institute at Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Leif Nelin, MD    614-355-6724      
Principal Investigator: Leif Nelin, MD         
United States, Pennsylvania
Univeristy of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara Schmidt, MD    215-662-3228      
Principal Investigator: Barbara Schmidt, MD         
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island Not yet recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD    401-274-1122 ext 43200      
Principal Investigator: Abbot R. Laptook, MD         
United States, Texas
University of Texas Southwestern Medical Center at Dallas Not yet recruiting
Dallas, Texas, United States, 75235
Contact: Myra Myckoff, MD    214-648-3923      
Principal Investigator: Myra Wyckoff, MD         
University of Texas Health Science Center at Houston Not yet recruiting
Houston, Texas, United States, 77030
Contact: Kathleen A. Kennedy, MD MPH    713-500-6708      
Principal Investigator: Kathleen A. Kennedy, MD MPH         
Sub-Investigator: Jon E. Tyson, MD MPH         
Sponsors and Collaborators
Investigators
Principal Investigator: 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: Ron N Goldbert, 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: Kurt Schibler, MD Cincinnati Children's Medical Center
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: Pablo J Sanchez, MD University of Texas Southwestern Medical Center at Dalla
Principal Investigator: Kathleen A Kennedy, MD, MPH The University of Texas Health Science Center, Houston
Principal Investigator: Barbara Schmidt, MD, MSc University of Pennsylvania
Principal Investigator: Carl T D'Angio, MD University of Rochester
Principal Investigator: Uday Devaskar, MD University of California, Los Angeles
Principal Investigator: Leif Nelin, MD Research Institute at Nationwide Children's Hospital
Principal Investigator: William Truog, MD Children's Mercy Hospital-Kansas City, MO
  More Information

Additional Information:
No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01793129     History of Changes
Other Study ID Numbers: NICHD-NRN-0051, U10HD021364, U10HD040689, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027904, U10HD027880, U10HD034216, U10HD021373, U10HD040492, U10HD053109, U10HD040461, U10HD068244, U10HD068263, U10HD068270, U10HD068278, U10HD068284, U10HD036790
Study First Received: February 13, 2013
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration
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:
Ischemia
Hypothermia
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Hypoxia, Brain
Pathologic Processes
Body Temperature Changes
Signs and Symptoms
Central Nervous System Diseases
Nervous System Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 29, 2014