Preemie Hypothermia for Neonatal Encephalopathy

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.

Sponsors

Lead Sponsor: NICHD Neonatal Research Network

Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Source NICHD Neonatal Research Network
Brief 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.

Detailed 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.

Overall Status Recruiting
Start Date May 2015
Completion Date October 2022
Primary Completion Date August 2020
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Death or moderate or severe disability Birth to 18-22 months corrected age
Secondary Outcome
Measure Time Frame
Number of deaths in the NICU and following discharge Birth to 18-22 months corrected age
Differences in MRI findings after cessation of cooling/control obtained Birth to 40 weeks corrected age
Number of infants with moderate and severe disability Birth to 18-22 months corrrected age
Causes of Death Birth to 18-22 months corrrected age
Neurological injury by cranial ultrasound within 24 hours of enrollment Birth to 2 days of life
Enrollment 168
Condition
Intervention

Intervention Type: Device

Intervention Name: Hypothermia

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

Arm Group Label: Whole-body Hypothermia

Intervention Type: Procedure

Intervention Name: Normothermic Control

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

Arm Group Label: Normothermia

Eligibility

Criteria:

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

Gender: All

Minimum Age: 33 Weeks

Maximum Age: 35 Weeks

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Roger G Faix, MD

Phone: 801-581-7052

Location
Facility: Status: Contact: Investigator:
University of Alabama at Birmingham | Birmingham, Alabama, 35233, United States Recruiting Waldemar A. Carlo, MD Waldemar A. Carlo, MD Principal Investigator
Stanford University | Palo Alto, California, 94304, United States Recruiting Krisa P. Van Meurs, MD Krisa P. Van Meurs, MD Principal Investigator
Emory University | Atlanta, Georgia, 30303, United States Recruiting David P Carlton, MD David P Carlton, MD Principal Investigator
Indiana University | Indianapolis, Indiana, 46202, United States Active, not recruiting
University of Iowa | Iowa City, Iowa, 52242, United States Recruiting Edward F. Bell, MD Edward F. Bell, MD Principal Investigator
Wayne State University | Detroit, Michigan, 48201, United States Active, not recruiting
University of New Mexico | Albuquerque, New Mexico, 87131, United States Recruiting Kristi L. Watterberg, MD Kristi L. Watterberg, MD Principal Investigator
University of Rochester | Rochester, New York, 14642, United States Recruiting Carl T D'Angio, MD Carl T D'Angio, MD Principal Investigator
RTI International | Durham, North Carolina, 27705, United States Active, not recruiting
Duke University | Durham, North Carolina, 27710, United States Recruiting C. Michael Cotten, MD C. Michael Cotten, MD MHS Sub-Investigator
Cincinnati Children's Medical Center | Cincinnati, Ohio, 45267, United States Recruiting Brenda Poindiexter, MD Brenda Poindexter, MD Principal Investigator
Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland, Ohio, 44106, United States Recruiting Michele C. Walsh, MD, MS Michele C. Walsh, MD MS Principal Investigator
Research Institute at Nationwide Children's Hospital | Columbus, Ohio, 43205, United States Recruiting Pablo Sanchez, MD Pablo Sanchez, MD Principal Investigator
Univeristy of Pennsylvania | Philadelphia, Pennsylvania, 19104, United States Recruiting Eric Eichenwald, MD Eric Eichenwald, MD Principal Investigator
Brown University, Women & Infants Hospital of Rhode Island | Providence, Rhode Island, 02905, United States Recruiting Abbot R. Laptook, MD Abbot R. Laptook, MD Principal Investigator
University of Texas Southwestern Medical Center at Dallas | Dallas, Texas, 75235, United States Recruiting Myra Myckoff, MD Myra Wyckoff, MD Principal Investigator
University of Texas Health Science Center at Houston | Houston, Texas, 77030, United States Recruiting Jon E Tyson, MD MPH Jon E. Tyson, MD MPH Principal Investigator
University of Utah | Salt Lake City, Utah, 84108, United States Recruiting Bradley Yoder, MD Bradley A. Yoder, MD Principal Investigator
Location Countries

United States

Verification Date

November 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Whole-body Hypothermia

Type: Experimental

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

Label: Normothermia

Type: Placebo Comparator

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

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov