Recombinant human erythropoietin (Epo) is a promising novel neuroprotective agent. Epo
decreases neuronal programmed cell death resulting from brain injury; it has
anti-inflammatory effects, increases neurogenesis, and protects oligodendrocytes from injury.
We hypothesize that neonatal Epo treatment of ELGANs will decrease the combined outcome of
death or severe NDI from 40% to 30% (primary outcome), or the combined outcome of death plus
moderate or severe NDI from 60% to 40% (secondary outcome) measured at 24-26 months corrected
age.
1. To determine whether Epo decreases the combined outcome of death or NDI at 24-26 months
corrected age. NDI is defined as the presence of any one of the following: CP, Bayley
Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Scale < 70
(severe, 2 SD below mean) or 85 (moderate, 1 SD below mean). CP will be diagnosed and
classified by standardized neurologic exam, with severity classified by Gross Motor
Function Classification System (GMFCS).
2. To determine whether there are risks to Epo administration in ELGANs by examining, in a
blinded manner, Epo-related safety measures comparing infants receiving Epo with those
given placebo.
3. To test whether Epo treatment decreases serial measures of circulating inflammatory
mediators, and biomarkers of brain injury.
4. To compare brain structure (as measured by MRI) in Epo treatment and control groups at
36 weeks PMA. MRI assessments will include documentation of intraventricular hemorrhage
(IVH), white matter injury (WMI) and hydrocephalus (HC), volume of total and deep gray
matter, white matter and cerebellum, brain gyrification, and tract-based spatial
statistics (TBSS based on diffusion tensor imaging). As an exploratory aim, we will
determine which of the above MRI measurements best predict neurodevelopment (CP,
cognitive and motor scales) at 24-26 months corrected age.
Anticipated outcomes: Early Epo treatment of ELGANs will decrease biochemical and MRI markers
of brain injury, will be safe, and will confer improved neurodevelopmental outcome at 24-26
months corrected age compared to placebo, and will provide a much-needed therapy for this
group of vulnerable infants.
Phase:
Phase 3
Details
Lead Sponsor:
University of Washington
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)