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

Hypoxic-ischemic Encephalopathy Clinical Trial

— NEATO  

Official title:

Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01913340
• Other study ID #: P0055603-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2013
• Est. completion date: September 2016

Study information

• Verified date: June 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Birth Asphyxia
• Brain Diseases
• Brain Ischemia
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic-ischemic Encephalopathy
• Neonatal Encephalopathy

Intervention

Drug:
• Erythropoietin
1000 U/kg/dose IV x 5 doses
• Normal saline
placebo: NS IV x 5 doses

Locations

Country	Name	City	State
United States	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	Stanford University	Palo Alto	California
United States	Washington University	Saint Louis	Missouri
United States	UCSF	San Francisco	California
United States	Kaiser Permanente, Santa Clara	Santa Clara	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (8)

Lead Sponsor	Collaborator
University of California, San Francisco	Arkansas Children's Hospital Research Institute, Children's National Research Institute, Kaiser Permanente, Seattle Children's Hospital, Stanford University, Thrasher Research Fund, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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). pii: e20160191. doi: 10.1542/peds.2016-0191. Epub 2016 May 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Warner Initial Developmental Evaluation (WIDEA)	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.	12 months
Primary	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	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.	12 months