Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)
Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain
About this trial
This is an interventional treatment trial for Infant, Newborn focused on measuring NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia, Fetal acidosis
Eligibility Criteria
Inclusion Criteria:
Eligibility will be determined in a stepped process:
- 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.
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.
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.
Sites / Locations
- University of Alabama at Birmingham
- University of California - Los Angeles
- Stanford University
- Emory University
- Indiana University
- University of Iowa
- Wayne State University
- Children's Mercy Hospital
- University of New Mexico
- University of Rochester
- RTI International
- Duke University
- Cincinnati Children's Medical Center
- Case Western Reserve University, Rainbow Babies and Children's Hospital
- Research Institute at Nationwide Children's Hospital
- Univeristy of Pennsylvania
- Brown University, Women & Infants Hospital of Rhode Island
- University of Texas Southwestern Medical Center at Dallas
- University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Experimental
Experimental
33.5°C for 72 hours
33.5°C for 120 hours
32.0°C for 72 hours
32.0°C for 120 hours
Target Temp: 33.5°C Duration: 72 hrs
Target Temp: 33.5°C Duration: 120 hrs
Target Temp: 32.0°C Duration: 72 hrs
Target Temp: 32.0°C Duration:120 hrs