Clinical trial NCT01913340: Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO)
Official title: Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypoxic-ischemic Encephalopathy
Neonatal Encephalopathy
Birth Asphyxia
Keywords: erythropoietin
therapeutic hypothermia
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
name: Seattle Children's Hospital
name: Arkansas Children's Hospital Research Institute
name: Washington University School of Medicine
name: Children's National Research Institute
name: Stanford University
name: Kaiser Permanente
First posted: 2013-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 30
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. 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.
2. The safety of high-dose Epo therapy in neonates with HIE with respect to systemic organ function and general growth parameters.
3. The value of brain MRI/MRS performed at 4-7 days of age as a biomarker of motor function at 12 months of age.

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:

  1. 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;
  2. 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
  3. 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.

Primary outcomes:
measure: Markers of Organ Function
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Secondary outcomes:
measure: Alberta Infant Motor Scale (AIMS)
timeFrame: 12 months
Other outcomes:
measure: Warner Initial Developmental Evaluation (WIDEA)
timeFrame: 12 months
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Institute
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente, Santa Clara
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: University of California, San Francisco
name: Yvonne W Wu, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.