Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)

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.

Conditions

• Extreme Prematurity

Interventions

DRUG

Epo

Enrollment will occur within 24 hours of birth. Study drug will be administered intravenously for the first 6 doses. Subjects in the Epo arm will then receive 400 U/kg/dose three times a week until they reach 32-6/7 weeks postmenstrual age. Control infants will receive sham injections.

OTHER

Control

Subjects will receive 6 doses of vehicle intravenously during the first 2 weeks of life. Doses will be administered at 48 hour intervals from the time of enrollment. Following high dose administration, sham subcutaneous injections will be given three times a week through to 32-6/7 weeks postmenstrual age.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• University of Washington

  lead OTHER

Principal Investigators

• Sandra E Juul, MD, PhD · University of Washington

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

24 Weeks

Max Age

27 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-12-31

Primary Completion

2019-02-28

Completion

2020-02-28

Countries

• United States

Study Locations