©2022 Stanford Medicine
Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)
Trial ID: NCT01192776
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.
Optimizing Cooling Strategies at < 6 Hours of Age for Neonatal Hypoxic-Ischemic Encephalopathy
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
- 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.
- 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.
procedure: Whole-body Cooling
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
M Bethany Ball