Evaluation of Systemic Hypothermia Initiated After 6 Hours of Age in Infants > or equal to 36 Weeks Gestation with Hypoxic-Ischemic Encephalopathy: A Bayesian Evaluation (Late Hypothermia Study for HIE)

Study ID
STU 122010-090

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Diana Vasil
214-648-3789
diana.vasil@utsouthwestern.edu

Principal Investigator
Myra Wyckoff

Summary

infants who have moderate to severe encephalopathy detected at 6 to 24 hours of age will be eligible for enrollment. after a neurological exam is performed and informed consent is obtained, infants will be randomized to either an esophageal temperature of 37.0[Degrees]C (control) or an esophageal temperature of 33.5[Degrees]C for 96 hours (cooling). infants will then be stratified by age at enrollment ([Less Than] 12 or [Greater Than]12 hours) and stage of encephalopathy (moderate or severe). Randomization will be determined by a computerized system during a telephone call, by research personnel, to the research data center. The mother's and infant's charts will be examined to collect specific data for the case report forms. aside from cooling, all subjects will receive standard of care treatments and management for Hie and its complications.
The primary outcome with be death or moderate/severe disability at 18 months of age. Severe disability will be defined by any of the following: a Bayley MDi [Less Than] 70, Gross Motor Function (GMF) level of 3-5, blindness or profound hearing loss requiring amplification. Moderate disability will be defined as a Bayley MDi between 70-84 and either a GMF level of 2, a seizure disorder or hearing deficit. infants without the primary outcome will be categorized as normal or mildly impaired. normal will be defined by an MDi [Greater Than] 85, GMF level 1, and absence of any neurosensory deficits. Mild impairment will be defined by either an MDi of 70-84 alone, or an MDi [Greater Than] 85 and any of the following: presence of a GMF level 2, seizure disorder or hearing loss not requiring amplification.
The neonatal Research network consists of 16 centers in the united States. it is estimated that this multicenter, randomized trial will enroll a total of 168 infants (84 per group) in 3 years. at this site, we anticipate that we will enroll approximately 15 infants in each arm (total 30). The first year of the trial will be considered a pilot phase due to the uncertainty of enrollment. if enrollment is excessively low, the trial may be discontinued.

Participant Eligibility

1. All term infants (>36 weeks gestation) will be screened for study entry if they are admitted to the NICU with an admitting diagnosis of neonatal depression, acute perinatal asphyxia encephalopathy or any other term used in the NICU that may be associated with hypoxia, ischemia or acidemia.
2. Inborn and outborn infants will be evaluated.
3. All infants < 24 hours of age will be screened for inclusion and exclusion
criteria.
4. Inclusion Criteria
Infants will be evaluated in two steps; evaluation by clinical and biochemical criteria (Step A), followed
by neurological exam (Step B).
A. All infants will be evaluated for the following:
1. History of an acute perinatal event (abruptio placenta, cord prolapse, severe FHR abnormality:
variable or late decelerations).
2. An Apgar score <5 at 10 minutes.
3. Cord pH or any postnatal blood gas pH at <1 hour <7.0.
4. Base deficit on cord gas or any postnatal blood gas at <1 hour >16 mEq/L.
5. Continued need for ventilation initiated at birth and continued for at least 10 minutes.
IF BLOOD GAS IS AVAILABLE:
IF BLOOD GAS IS NOT AVAILABLE, OR
pH 7.01 to 7.15, OR
BASE DEFICIT 10 to 15.9mEq/L
A1 A2

* Cord pH or any postnatal blood gas pH <7.0
* Acute perinatal event
OR AND

* Base deficit on cord pH or any postnatal blood
gas at >16 mEq/L

* An Apgar score <5 at 10 minutes OR

* Continued need for ventilation initiated at
birth and continued for at least 10 minutes
If the criteria in A1 or A2 are met, proceed to the neurological examination.
B. The presence of moderate/severe encephalopathy defined as seizures OR presence of one or more
signs in three of the six categories (level of consciousness, spontaneous activity, posture, tone,
primitive reflexes and autonomic system).
Infants should be examined even in the presence of seizures since the level of encephalopathy
needs to be determined.
Category Moderate Encephalopathy Severe Encephalopathy
1. Level of consciousness Lethargic Stupor/coma
2. Spontaneous activity Decreased No activity
3. Posture Distal flexion, full extension Decerebrate
4. Tone a. Hypotonia (focal, general)
b. Hypertonia
a. Flaccid
b. Rigid
5. Primitive reflexes
Suck
Moro
Weak
Incomplete
Absent
Absent
6. Autonomic system
Pupils
Heart rate
Respirations
Constricted
Bradycardia
Periodic breathing
Skew deviation/dilated/non-reactive to light
Variable HR
Apnea
The neurological examination will be performed by a physician examiner. To facilitate the accuracy of the neurological examination, every attempt should be made to withhold the administration of
medications that may alter the examination (e.g., versed, fentanyl etc) until after the exam is completed unless imperative for clinical care. If infant meets criteria A1 or A2 and criteria B and does not meet exclusion criteria, the infant is eligible for study entry. If consent is obtained, infant will be randomized to the cooled or control group.