Preemie Hypothermia for Neonatal Encephalopathy

Infant, Newborn Clinical Trial

Official title:

A Randomized Trial of Targeted Temperature Management With Whole Body Hypothermia For Moderate And Severe Hypoxic-Ischemic Encephalopathy In Premature Infants 33-35 Weeks Gestational Age.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01793129
• Other study ID #: NICHD-NRN-0051
• Secondary ID: U10HD021364U10HD
• Status: Completed
• Phase: N/A
• Start date: May 2015
• Est. completion date: December 9, 2022

Study information

• Verified date: April 2024
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: December 9, 2022
• Est. primary completion date: December 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 33 Weeks to 35 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Encephalopathy, Hypoxic-Ischemic
• Hypothermia
• Hypoxia
• Hypoxia, Brain
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Infant, Newborn
• Ischemia
• Ischemic-Hypoxic Encephalopathy

Intervention

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

Procedure:
• Normothermic Control
Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Stanford University	Palo Alto	California
United States	Univeristy of Pennsylvania	Philadelphia	Pennsylvania
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or Moderate or Severe Disability	Severe disability was defined by any of the following: a Bayley III cognitive score < 70 or Gross Motor Function (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to following commands/communicate. Moderate disability was defined as a Bayley III cognitive score between 70-84 and either a GMF level of 2 or a seizure disorder or a hearing deficit.	Birth to 18-22 months corrected age
Secondary	Number of Deaths in the NICU and Following Discharge	Number of deaths in the NICU and following discharge among infants with a primary outcome.	Birth to 18-22 months corrected age
Secondary	Number of Infants With Abnormal MRIs During Post-intervention Period	An MRI was considered abnormal if any abnormal findings were indicated on the CRF form.	Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days
Secondary	Number of Infants With Moderate or Severe Disability	Number of infants with moderate or severe disability among survivors through 18-22 months corrected age.	Birth to 18-22 months corrrected age
Secondary	Causes of Death	Causes of any deaths that occurred through 18-22 months corrected age.	Birth to 18-22 months corrrected age
Secondary	Neurological Injury by Cranial Ultrasound During Intervention	Infants with recorded events of intraventricular hemorrhage grade I, II, III, or IV, posterior fossa hemorrhage with/without shift of midline structures, intraparenchymal hemorrhage.	Within 6 hours of life to 72 hours after start of intervention

External Links

•   Neonatal Research Network website