Preemie Hypothermia for Neonatal Encephalopathy

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01793129

Collaborator

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

168

Enrollment

Locations

Arms

Duration (Months)

9.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infant, Newborn Hypoxia, Brain Hypoxia-Ischemia, Brain Encephalopathy, Hypoxic-Ischemic Hypoxic-Ischemic Encephalopathy Ischemic-Hypoxic Encephalopathy	Device: Hypothermia Procedure: Normothermic Control	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

168 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

May 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Device: Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours
Placebo Comparator: Normothermia Control group (with esophageal temperature at or near 37.0°C) for 72 hours	Procedure: Normothermic Control Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours

Arm

Intervention/Treatment

Experimental: Whole-body Hypothermia

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

Device: Hypothermia

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

Placebo Comparator: Normothermia

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

Procedure: Normothermic Control

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

Outcome Measures

Primary Outcome Measures

Death or moderate or severe disability [Birth to 18-22 months corrected age]

Secondary Outcome Measures

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]
withdrawal of support and reasons for such will be tracked; attempts will be made to obtain autopsy whenever possible
Neurological injury by cranial ultrasound within 24 hours of enrollment [Birth to 2 days of life]

Eligibility Criteria

Criteria

Ages Eligible for Study:

33 Weeks to 35 Weeks

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	Emory University	Atlanta	Georgia	United States	30303
4	Indiana University	Indianapolis	Indiana	United States	46202
5	University of Iowa	Iowa City	Iowa	United States	52242
6	Wayne State University	Detroit	Michigan	United States	48201
7	University of New Mexico	Albuquerque	New Mexico	United States	87131
8	University of Rochester	Rochester	New York	United States	14642
9	RTI International	Durham	North Carolina	United States	27705
10	Duke University	Durham	North Carolina	United States	27710
11	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
12	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
13	Research Institute at Nationwide Children's Hospital	Columbus	Ohio	United States	43205
14	Univeristy of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
16	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
17	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
18	University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

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

Investigators

Principal Investigator: Michele C Walsh, MD, Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Seetha Shankaran, MD, Wayne State University
Principal Investigator: Abbot R Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: C. Michael Cotten, MD, Duke University
Principal Investigator: David P Carlton, MD, Emory University
Principal Investigator: Greg Sokol, MD, MS, Indiana University
Principal Investigator: Abhik Das, PhD, RTI International
Principal Investigator: Krisa P Van Meurs, MD, Stanford University
Principal Investigator: Brenda Poindexter, MD, Children's Hospital Medical Center, Cincinnati
Principal Investigator: Wally A Carlo, MD, University of Alabama at Birmingham
Principal Investigator: Edward F Bell, MD, University of Iowa
Principal Investigator: Kristi L Watterberg, MD, University of New Mexico
Principal Investigator: Myra Wyckoff, MD, University of Texas Southwestern Medical Center at Dalla
Principal Investigator: Jon E Tyson, MD, MPH, The University of Texas Health Science Center, Houston
Principal Investigator: Eric Eichenwald, MD, University of Pennsylvania
Principal Investigator: Carl T D'Angio, MD, University of Rochester
Principal Investigator: Pablo Sanchez, MD, Research Institute at Nationwide Children's Hospital
Principal Investigator: Bradley Yoder, MD, University of Utah