Preemie Hypothermia for Neonatal Encephalopathy

NICHD Neonatal Research Network

Status: Completed

Conditions: Infant, Newborn; Ischemic-Hypoxic Encephalopathy; Hypoxia-Ischemia, Brain; Hypoxic-Ischemic Encephalopathy; Encephalopathy, Hypoxic-Ischemic; Hypoxia, Brain

Treatments: Procedure: Normothermic Control; Device: Hypothermia

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01793129

U10HD053109 (U.S. NIH Grant/Contract)

U10HD021373 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

U10HD068270 (U.S. NIH Grant/Contract)

U10HD021364 (U.S. NIH Grant/Contract)

NICHD-NRN-0051

U10HD027880 (U.S. NIH Grant/Contract)

U10HD036790 (U.S. NIH Grant/Contract)

U10HD027856 (U.S. NIH Grant/Contract)

U10HD040492 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD068244 (U.S. NIH Grant/Contract)

U10HD040689 (U.S. NIH Grant/Contract)

UG1HD087226 (U.S. NIH Grant/Contract)

U10HD068284 (U.S. NIH Grant/Contract)

U10HD068263 (U.S. NIH Grant/Contract)

U10HD034216 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

U10HD068278 (U.S. NIH Grant/Contract)

U10HD040461 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Secondary Study includes determining an association between MRI detectable injury and neurodevelopment at 18-22 months.

Enrollment: 168 patients

Sex: All

Ages: 33 to 35 weeks old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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168 participants in 2 patient groups, including a placebo group

Whole-body Hypothermia

Experimental group

Description:

Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours

Treatment:

Device: Hypothermia

Normothermia

Placebo Comparator group

Description:

Control group (with esophageal temperature at or near 37.0°C) for 72 hours

Treatment:

Procedure: Normothermic Control