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

NCT ID: NCT01913340

Last Updated: 2020-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-09-30

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.

Conditions

Hypoxic-ischemic Encephalopathy; Neonatal Encephalopathy; Birth Asphyxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Erythropoietin

1000 U/kg/dose x 5 doses

Group Type: ACTIVE_COMPARATOR

Erythropoietin

Intervention Type: DRUG

1000 U/kg/dose IV x 5 doses

Normal saline

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

placebo: NS IV x 5 doses

Interventions

Erythropoietin

1000 U/kg/dose IV x 5 doses

Intervention Type: DRUG

Normal saline

placebo: NS IV x 5 doses

Intervention Type: DRUG

Other Intervention Names

Procrit

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 30 Minutes
• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

Arkansas Children's Hospital Research Institute

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

Children's National Research Institute

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Kaiser Permanente

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvonne W Wu, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, United States

Stanford University

Palo Alto, California, United States

UCSF

San Francisco, California, United States

Kaiser Permanente, Santa Clara

Santa Clara, California, United States

Children's National Medical Center

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

Washington University

St Louis, Missouri, United States

Seattle Children's Hospital

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23008465 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27244862 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28456387 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24684556 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29478510 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31261373 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30661082 (View on PubMed)

Other Identifiers

P0055603-01

Identifier Type: -

Identifier Source: org_study_id