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Preemie Hypothermia for Neonatal Encephalopathy

Primary Purpose

Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Hypothermia

Normothermic Control

About this trial

This is an interventional treatment trial for Infant, Newborn focused on measuring NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia

Eligibility Criteria

33 Weeks - 35 Weeks (Child)All SexesDoes not accept 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

Sites / Locations

University of Alabama at Birmingham
Stanford University
Emory University
Indiana University
University of Iowa
Wayne State University
University of New Mexico
University of Rochester
RTI International
Duke University
Cincinnati Children's Medical Center
Case Western Reserve University, Rainbow Babies and Children's Hospital
Research Institute at Nationwide Children's Hospital
Univeristy of Pennsylvania
Brown University, Women & Infants Hospital of Rhode Island
University of Texas Southwestern Medical Center at Dallas
University of Texas Health Science Center at Houston
University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Whole-body Hypothermia

Normothermia

Arm Description

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

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

Outcomes

Primary Outcome Measures

Death or moderate or severe disability

Secondary Outcome Measures

Number of deaths in the NICU and following discharge

Differences in MRI findings after cessation of cooling/control obtained

Number of infants with moderate and severe disability

Causes of Death

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

Full Information

NCT ID

NCT01793129

First Posted

February 13, 2013

Last Updated

December 19, 2022

Sponsor

NICHD Neonatal Research Network

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01793129

Brief Title

Preemie Hypothermia for Neonatal Encephalopathy

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 Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

December 9, 2022 (Actual)

Study Completion Date

December 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NICHD Neonatal Research Network

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infant, Newborn, Hypoxia, Brain, Hypoxia-Ischemia, Brain, Encephalopathy, Hypoxic-Ischemic, Hypoxic-Ischemic Encephalopathy, Ischemic-Hypoxic Encephalopathy

Keywords

NICHD Neonatal Research Network, Hypoxic-ischemic encephalopathy (HIE), Hypothermia, Neonatal depression, Perinatal asphyxia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

168 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Whole-body Hypothermia

Arm Type

Experimental

Arm Description

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

Arm Title

Normothermia

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Device

Intervention Name(s)

Hypothermia

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Normothermic Control

Intervention Description

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

Primary Outcome Measure Information:

Title

Death or moderate or severe disability

Time Frame

Birth to 18-22 months corrected age

Secondary Outcome Measure Information:

Title

Number of deaths in the NICU and following discharge

Time Frame

Birth to 18-22 months corrected age

Title

Differences in MRI findings after cessation of cooling/control obtained

Time Frame

Birth to 40 weeks corrected age

Title

Number of infants with moderate and severe disability

Time Frame

Birth to 18-22 months corrrected age

Title

Causes of Death

Description

withdrawal of support and reasons for such will be tracked; attempts will be made to obtain autopsy whenever possible

Time Frame

Birth to 18-22 months corrrected age

Title

Neurological injury by cranial ultrasound within 24 hours of enrollment

Time Frame

Birth to 2 days of life

10. Eligibility

Sex

All

Minimum Age & Unit of Time

33 Weeks

Maximum Age & Unit of Time

35 Weeks

Accepts Healthy Volunteers

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

Overall Study Officials: