drugset / Trial / NCT01378273

Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)

Phase 3 Completed 941 enrolled University of Washington National Institute of Neurological Disorders and Stroke (NINDS) · collab

RandomizedParallel-groupQuadruple-blindTreatment

Summary

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.

Timeline

Start: 2013-12
Primary completion: 2019-02-28
Completion: 2020-02-28

Outcome

Missed primary endpoint

registry p = 0.05; Risk Ratio (RR) 1.03 (.05% CI 0.81 to 1.32) NCT01378273 ↗

paper There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment PMID 31940698 ↗

Publications

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Epo	Protein / enzyme biologic	400 iu/kg	Intravenous