Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)
Condition: Extreme Prematurity
MeSH terms: Premature Birth
Intervention: Epo; Control
Intervention description: 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.; 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.
Intervention MeSH terms: Epoetin Alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 941.0
Sex: All
Minimum age: 24 Weeks
Maximum age: 27 Weeks
Healthy volunteers: No
Keywords: neuroprotection; erythropoietin; Epo; ELGANs; preterm; neonate

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. NICU inpatients between 24-0/7 and 27-6/7 weeks of gestation

          2. Less than twenty four hours of age

          3. Parental informed consent

        Exclusion Criteria:

          1. Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)

          2. Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities

          3. Polycythemia (hematocrit > 65)

          4. Congenital infection