Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01192776
First received: August 31, 2010
Last updated: December 12, 2013
Last verified: December 2013

August 31, 2010
December 12, 2013
September 2010
September 2015   (final data collection date for primary outcome measure)
Death or Moderate to Severe Disability [ Time Frame: Birth to 22 months corrected age ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01192776 on ClinicalTrials.gov Archive Site
  • Death [ Time Frame: Birth to 22 months corrected age ] [ Designated as safety issue: Yes ]
  • Mild, moderate, and severe disability [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
    Number of infants with mild, moderate, and severe disability
  • Withdrawal of care [ Time Frame: Birth to hospital discharge ] [ Designated as safety issue: Yes ]
    Number of infants for whom aggressive care is withdrawn
  • Acute Adverse Events [ Time Frame: Until infant achieves normothermia ] [ Designated as safety issue: Yes ]
    Number of adverse events (severe bradycardia, acidosis, bleeding or ischemic CNS abnormalities)
  • Clinical neonatal seizures [ Time Frame: Until death, discharge, or transfer ] [ Designated as safety issue: Yes ]
  • Severe neonatal brain abnormalities [ Time Frame: 7-14 days of life ] [ Designated as safety issue: Yes ]
    MRIs taken between 7-14 days will be examined.
  • Cognitive outcome [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Cerebral palsy [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Disability by stage of HIE [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Visual impairment [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Hearing impairment [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Multiple Disabilities [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Multiorgan Dysfunction [ Time Frame: Until death, discharge, or transfer ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)
Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy

The Optimizing Cooling trial will compare four whole-body cooling treatments for infants born at 36 weeks gestational age or later with hypoxic-ischemic encephalopathy: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. The objective of this study is to evaluate whether whole-body cooling initiated at less than 6 hours of age and continued for 120 hours and/or a depth at 32.0°C in will reduce death and disability at 18-22 months corrected age.

Hypoxic-ischemic encephalopathy (HIE) is a rare, but life-threatening condition characterized by brain injury due to asphyxia 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. Up to 80 percent of infants who survive stage 3 HIE develop significant long-term disabilities, including intellectual disabilities, epilepsy, and cerebral palsy with hemiplegia, paraplegia, or quadriplegia; 10-20 percent develop moderately serious disabilities; and up to 10 percent are normal.

Previous studies have shown treatment with hypothermia to be an effective therapy for HIE. Currently, infants diagnosed with HIE at less than six hours of age are given whole-body cooling, decreasing their core body temperature to 33.5°C (93.2° Fahrenheit) for a period 72 hours using a cooling blanket. This treatment appears to protect the brain, decreasing the rate of death and disability and improving the chances of survival and neurodevelopmental outcomes at 18 months correct age. But additional trials are needed to help define the most effective cooling strategies.

The Optimizing Cooling trial will examine whether cooling for a longer time period and/or to a lower temperature will improve the chance of survival and neurodevelopmental outcomes at 18-22 months corrected age. Eligible infants with HIE will be placed in one of four cooling groups: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. Infants will be monitored closely and receive the care of the Neonatal Intensive Care Unit (NICU).

Infants enrolled in the study will be placed on a cooling blanket - the same type of blanket children's hospitals use in the NICU, in operating rooms during surgeries, and to cool children with high fevers. Each infant will be cooled according to the study group he or she is assigned to. During cooling, the infant's temperature will be very closely monitored by continuous esophageal (core)temperature readings. This will be done by placing a soft, narrow, flexible plastic tube into the infant's nose and down to just above the stomach. Skin temperatures will also be monitored closely. At the end of the assigned period of cooling, the infant will be slowly re-warmed until a normal core temperature of 36.5 to 37.0°C (97.7 to 98.6°C) is reached.

Infants will be examined at 18-22 months corrected age to assess their neurodevelopmental outcomes.

Secondary Studies include:

A. Using aEEG to 1)predict mortality or moderate to severe disability at 18-22 months in term infants with HIE treated with systemic hypothermia and 2) to record electrical seizure activity to compare rewarming initiated at 72 hours and later rewarming that is initiated at 120 hours.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Infant, Newborn
  • Hypoxia, Brain
  • Hypoxia-Ischemia, Brain
  • Encephalopathy, Hypoxic-Ischemic
  • Hypoxic-Ischemic Encephalopathy
  • Ischemic-Hypoxic Encephalopathy
Procedure: Whole-body Cooling
Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.
Other Names:
  • Blanketrol II Model 222R
  • Blanketrol III Model 233 (used in the II mode)
  • Active Comparator: 33.5°C for 72 hours
    Target Temp: 33.5°C Duration: 72 hrs
    Intervention: Procedure: Whole-body Cooling
  • Experimental: 33.5°C for 120 hours
    Target Temp: 33.5°C Duration: 120 hrs
    Intervention: Procedure: Whole-body Cooling
  • Experimental: 32.0°C for 72 hours
    Target Temp: 32.0°C Duration: 72 hrs
    Intervention: Procedure: Whole-body Cooling
  • Experimental: 32.0°C for 120 hours
    Target Temp: 32.0°C Duration:120 hrs
    Intervention: Procedure: Whole-body Cooling
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
726
September 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

Eligibility will be determined in a stepped process:

  1. All infants with a gestational age ≥ 36 weeks will be screened for study entry if they are admitted to the NICU with a diagnosis of fetal acidosis, perinatal asphyxia, neonatal depression or encephalopathy.
  2. Infants will be eligible if:

    • They have a pH ≤ 7.0 or a base deficit ≥ 16m mEq/ L on umbilical cord or any postnatal sample within 1 hour of age.
    • If, during this interval, they have a pH between 7.01 and 7.15, a base deficit is between 10 and 15.9 mEq/L, or a blood gas is not available, AND they have an acute perinatal event AND either a 10-minute Apgar score ≤ 5 or assisted ventilation initiated at birth and continued for at least 10 minutes.
  3. Once these criteria are met, eligible infants will have a standardized neurological examination performed by a certified physician examiner. Infants will be candidates for the study when encephalopathy or seizures are present. For this study, encephalopathy is defined as the presence of 1 or more signs in 3 of the following 6 categories:

    • Level of consciousness: lethargy, stupor or coma;
    • Spontaneous activity: decreased, absent;
    • Posture: distal flexion, decerebrate;
    • tone: hypotonia, flaccid or hypertonia, rigid;
    • Primitive reflexes: a) suck, weak, absent; b) Moro, incomplete, flaccid;
    • Autonomic nervous system: a) pupils: constricted, unequal, skew deviation or non reactive to light; b) heart rate: bradycardia, variable heart rate or c) respiration: periodic breathing, apnea.

Eligible infants from multiple births will be enrolled in the same arm of the study.

Exclusion Criteria:

  • Inability to randomize by 6 hours of age
  • Major congenital abnormality
  • Major chromosomal abnormality (including Trisomy 21),
  • Severe growth restriction (≤ 1800gm birth weight),
  • Infant is moribund and will not receive any further aggressive treatment,
  • Refusal of consent by parent
  • Refusal of consent by attending neonatologist
  • Infants with a core temperature < 33.5°C for > 1 hour at the time of screening by the research team would not be eligible for the study.
Both
up to 6 Hours
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01192776
NICHD-NRN-0043, U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880, U10HD027904, U10HD034216, U10HD036790, U10HD040492, U10HD040689, U10HD053089, U10HD053109, U10HD053119, U10HD053124, UL1RR024139, UL1RR024979, UL1RR025008, UL1RR025744, UL1RR025747, UL1RR025761, UL1RR025764, U10HD068284, U10HD068278, U10HD068270, U10HD068263, U10HD068244
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Study Chair: Seetha Shankaran, MD Wayne State University
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: 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: 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, MD Research Institute at Nationwide Children's Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP