Back to resultsNeonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO) (NEATO)
Primary Purpose
Hypoxic-ischemic Encephalopathy, Neonatal Encephalopathy, Birth Asphyxia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Erythropoietin
Normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Hypoxic-ischemic Encephalopathy focused on measuring erythropoietin, therapeutic hypothermia
Eligibility Criteria
Inclusion Criteria:
Newborns ≥ 36 weeks gestation, < 23 hours of age at time of consent, must meet all 3 Inclusion Criteria to be eligible for the study:
- Perinatal depression = at least one of the following: a) Apgar ≤5 at 10 min or b) required resuscitation (endotracheal or mask ventilation, or chest compressions) at 10 min or c) pH < 7.0 or base deficit ≥15 in cord, arterial, or venous blood obtained at <60 min of age;
- Moderate to severe encephalopathy = at least 3 of 6 modified Sarnat criteria present between 1-6 h of birth: a) reduced level of consciousness; b) decreased spontaneous activity; c) hypotonia; d) decreased suck; e) decreased Moro reflex; or f) respiratory distress including periodic breathing or apnea; and
- Hypothermia = passive or active cooling begun by 6 hours of age.
Exclusion Criteria:
- Intrauterine growth restriction (BW <1800 g);
- Major congenital malformation; suspected genetic syndrome, metabolic disorder or TORCH infection;
- Head circumference < 2 SD for gestation;
- Infant for whom withdrawal of supportive care is being considered; or
- Anticipated inability to collect primary endpoint at 12 months of age.
Sites / Locations
- Arkansas Children's Hospital Research Institute
- Stanford University
- UCSF
- Kaiser Permanente, Santa Clara
- Children's National Medical Center
- Washington University
- Seattle Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Erythropoietin
Normal saline
Arm Description
1000 U/kg/dose x 5 doses
Outcomes
Primary Outcome Measures
Markers of Organ Function
The investigators will monitor organ function and adverse events until hospital discharge from the neonatal intensive care unit
Secondary Outcome Measures
Alberta Infant Motor Scale (AIMS)
The AIMS consists of 58 items, including 4 positions: prone (21 items), supine (9 items), sitting (12 items), & standing (16 items). Each item is scored as 'observed' or 'not observed'. Total score range is 0-58, scored as percentile ranks after a raw score is obtained and plotted against age at testing, based on validated norms.
Full Information
NCT ID
NCT01913340
First Posted
July 29, 2013
Last Updated
June 26, 2020
Sponsor
University of California, San Francisco
Collaborators
Thrasher Research Fund, Seattle Children's Hospital, Arkansas Children's Hospital Research Institute, Washington University School of Medicine, Children's National Research Institute, Stanford University, Kaiser Permanente
1. Study Identification
Unique Protocol Identification Number
NCT01913340
Brief Title
Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO)
Acronym
NEATO
Official Title
Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Thrasher Research Fund, Seattle Children's Hospital, Arkansas Children's Hospital Research Institute, Washington University School of Medicine, Children's National Research Institute, Stanford University, Kaiser Permanente
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Hypoxic-ischemic encephalopathy (HIE), a condition of reduced blood and oxygen flow to a baby's brain near the time of birth, may cause death or neurologic disability. Cooling therapy (hypothermia) provides some protection, but about half of affected infants still have a poor outcome. This clinical trial will determine if the drug erythropoietin, given with hypothermia, is safe to use as a treatment that may further reduce the risk of neurologic deficits after HIE.
Detailed Description
This phase I/II clinical trial is designed to demonstrate:
The feasibility of recruiting, enrolling and following 50 patients with moderate to severe HIE at 5 sites, while meeting specified recruitment and follow-up target goals.
The safety of high-dose Epo therapy in neonates with HIE with respect to systemic organ function and general growth parameters.
The value of brain MRI/MRS performed at 4-7 days of age as a biomarker of motor function at 12 months of age.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic-ischemic Encephalopathy, Neonatal Encephalopathy, Birth Asphyxia
Keywords
erythropoietin, therapeutic hypothermia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Erythropoietin
Arm Type
Active Comparator
Arm Description
1000 U/kg/dose x 5 doses
Arm Title
Normal saline
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Erythropoietin
Other Intervention Name(s)
Procrit
Intervention Description
1000 U/kg/dose IV x 5 doses
Intervention Type
Drug
Intervention Name(s)
Normal saline
Intervention Description
placebo: NS IV x 5 doses
Primary Outcome Measure Information:
Title
Markers of Organ Function
Description
The investigators will monitor organ function and adverse events until hospital discharge from the neonatal intensive care unit
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Secondary Outcome Measure Information:
Title
Alberta Infant Motor Scale (AIMS)
Description
The AIMS consists of 58 items, including 4 positions: prone (21 items), supine (9 items), sitting (12 items), & standing (16 items). Each item is scored as 'observed' or 'not observed'. Total score range is 0-58, scored as percentile ranks after a raw score is obtained and plotted against age at testing, based on validated norms.
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Warner Initial Developmental Evaluation (WIDEA)
Description
A 43-item questionnaire developed and standardized to assess the functional domains of self-care, motor function, communication and social cognition in young children. Self care sub-scale score range 17-68. Mobility score range is 9-36. Communication score range is 13-52. Social Cognition score range is 11-44. Total scale range is 50-200. Higher scores mean higher functioning. Lower scores mean lower functioning.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Minutes
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newborns ≥ 36 weeks gestation, < 23 hours of age at time of consent, must meet all 3 Inclusion Criteria to be eligible for the study:
Perinatal depression = at least one of the following: a) Apgar ≤5 at 10 min or b) required resuscitation (endotracheal or mask ventilation, or chest compressions) at 10 min or c) pH < 7.0 or base deficit ≥15 in cord, arterial, or venous blood obtained at <60 min of age;
Moderate to severe encephalopathy = at least 3 of 6 modified Sarnat criteria present between 1-6 h of birth: a) reduced level of consciousness; b) decreased spontaneous activity; c) hypotonia; d) decreased suck; e) decreased Moro reflex; or f) respiratory distress including periodic breathing or apnea; and
Hypothermia = passive or active cooling begun by 6 hours of age.
Exclusion Criteria:
Intrauterine growth restriction (BW <1800 g);
Major congenital malformation; suspected genetic syndrome, metabolic disorder or TORCH infection;
Head circumference < 2 SD for gestation;
Infant for whom withdrawal of supportive care is being considered; or
Anticipated inability to collect primary endpoint at 12 months of age.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvonne W Wu, MD, MPH
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arkansas Children's Hospital Research Institute
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Kaiser Permanente, Santa Clara
City
Santa Clara
State/Province
California
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23008465
Citation
Wu YW, Bauer LA, Ballard RA, Ferriero DM, Glidden DV, Mayock DE, Chang T, Durand DJ, Song D, Bonifacio SL, Gonzalez FF, Glass HC, Juul SE. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics. 2012 Oct;130(4):683-91. doi: 10.1542/peds.2012-0498. Epub 2012 Sep 24.
Results Reference
background
PubMed Identifier
27244862
Citation
Wu YW, Mathur AM, Chang T, McKinstry RC, Mulkey SB, Mayock DE, Van Meurs KP, Rogers EE, Gonzalez FF, Comstock BA, Juul SE, Msall ME, Bonifacio SL, Glass HC, Massaro AN, Dong L, Tan KW, Heagerty PJ, Ballard RA. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics. 2016 Jun;137(6):e20160191. doi: 10.1542/peds.2016-0191. Epub 2016 May 2.
Results Reference
background
PubMed Identifier
28456387
Citation
Mulkey SB, Ramakrishnaiah RH, McKinstry RC, Chang T, Mathur AM, Mayock DE, Van Meurs KP, Schaefer GB, Luo C, Bai S, Juul SE, Wu YW. Erythropoietin and Brain Magnetic Resonance Imaging Findings in Hypoxic-Ischemic Encephalopathy: Volume of Acute Brain Injury and 1-Year Neurodevelopmental Outcome. J Pediatr. 2017 Jul;186:196-199. doi: 10.1016/j.jpeds.2017.03.053. Epub 2017 Apr 26.
Results Reference
background
PubMed Identifier
24684556
Citation
Darrah J, Bartlett D, Maguire TO, Avison WR, Lacaze-Masmonteil T. Have infant gross motor abilities changed in 20 years? A re-evaluation of the Alberta Infant Motor Scale normative values. Dev Med Child Neurol. 2014 Sep;56(9):877-81. doi: 10.1111/dmcn.12452. Epub 2014 Mar 29.
Results Reference
background
PubMed Identifier
29478510
Citation
Massaro AN, Wu YW, Bammler TK, Comstock B, Mathur A, McKinstry RC, Chang T, Mayock DE, Mulkey SB, Van Meurs K, Juul S. Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2018 Mar;194:67-75.e1. doi: 10.1016/j.jpeds.2017.10.060.
Results Reference
background
PubMed Identifier
31261373
Citation
Wu YW, Goodman AM, Chang T, Mulkey SB, Gonzalez FF, Mayock DE, Juul SE, Mathur AM, Van Meurs K, McKinstry RC, Redline RW. Placental pathology and neonatal brain MRI in a randomized trial of erythropoietin for hypoxic-ischemic encephalopathy. Pediatr Res. 2020 Apr;87(5):879-884. doi: 10.1038/s41390-019-0493-6. Epub 2019 Jul 1.
Results Reference
result
PubMed Identifier
30661082
Citation
Massaro AN, Wu YW, Bammler TK, MacDonald JW, Mathur A, Chang T, Mayock D, Mulkey SB, van Meurs K, Afsharinejad Z, Juul SE. Dried blood spot compared to plasma measurements of blood-based biomarkers of brain injury in neonatal encephalopathy. Pediatr Res. 2019 Apr;85(5):655-661. doi: 10.1038/s41390-019-0298-7. Epub 2019 Jan 19.
Results Reference
result
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Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO)
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