Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO)

NCT01913340 | Completed Phase 1 Results FDA Drug

• 1 other identifier: P0055603-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

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.

Conditions

Hypoxic-ischemic Encephalopathy; Neonatal Encephalopathy; Birth Asphyxia

Keywords

erythropoietin; therapeutic hypothermia

Outcome Measures

Primary Outcomes (1)

• Markers of Organ Function

  The investigators will monitor organ function and adverse events until hospital discharge from the neonatal intensive care unit

  Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Secondary Outcomes (1)

• Alberta Infant Motor Scale (AIMS)

  12 months

Other Outcomes (1)

• Warner Initial Developmental Evaluation (WIDEA)

  12 months

Study Arms (2)

Erythropoietin

ACTIVE COMPARATOR

1000 U/kg/dose x 5 doses

Drug: Erythropoietin

Normal saline

PLACEBO COMPARATOR

Drug: Normal saline

Interventions

Erythropoietin DRUG

1000 U/kg/dose IV x 5 doses

Also known as: Procrit

Erythropoietin

Normal saline DRUG

placebo: NS IV x 5 doses

Normal saline

Eligibility Criteria

• Age: 30 Minutes - 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Thrasher Research Fund: collaborator
• Seattle Children's Hospital: collaborator
• Arkansas Children's Hospital Research Institute: collaborator
• Washington University School of Medicine: collaborator
• Children's National Research Institute: collaborator
• Stanford University: collaborator
• Kaiser Permanente: collaborator

Study Sites (7)

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, 72202, United States

Location

Stanford University

Palo Alto, California, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Kaiser Permanente, Santa Clara

Santa Clara, California, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (7)

• 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.

  PMID: 23008465 BACKGROUND

• 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.

  PMID: 27244862 BACKGROUND

• 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.

  PMID: 28456387 BACKGROUND

• 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.

  PMID: 24684556 BACKGROUND

• 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.

  PMID: 29478510 BACKGROUND

• 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.

  PMID: 31261373 RESULT

• 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.

  PMID: 30661082 RESULT

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia Neonatorum

Interventions

Erythropoietin; Epoetin Alfa; Saline Solution

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Yvonne Wu, MD MPH
• Organization: University of California San Francisco

wuy@ucsf.edu

Study Officials

• Yvonne W Wu, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: August 1, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: September 1, 2016
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-06

Locations

US (7)