Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants

advances in neonatal care have led to significant improvements in the survival of the nearly 60,000 very low birth weight (VLBW) infants born each year in the u.S.improving neurodevelopmental outcomes for these preterm infants continues to be a major goal for neonatal care providers. although a variety of neuroprotective treatment strategies have been evaluated, no specific treatment has been identified to reduce or prevent brain injury in these most vulnerable preterm infants. a potential neuroprotective therapy involves administering erythropoiesis stimulating agents (eSas) such as erythropoietin (epo) and Darbepoetin (Darbe, a longer acting eSa). in addition to stimulating erythropoiesis, eSas have been shown to be protective in the developing brain in animal models, making it possibly beneficial for very premature infants who are at risk for intraventricular hemorrhage, hypoxic-ischemic injury, and developmental delay. We previously published data suggesting a relationship between serum epo concentrations and cognitive outcomes in eLBW infants. Based on preliminary pharmacokinetic and erythrokinetic data on the administration of Darbe to preterm infants, we propose a randomized, masked, controlled study to evaluate effects on red cell mass and developmental preterm outcomes. enrolled infants will receive weekly Darbe or placebo (sham) dosing. Laboratory tests will be performed on all infants while in the hospital. Transfusions will be administered via protocol. neurodevelopmental assessment will be performed at 22-26 months. The primary outcome is the Bayley iii cognitive score. Deaths will be assigned a score of 54. The trial will analyze all enrolled infants as above, and will randomize infants 23 0/7-28 6/7 weeks Ga into two groups Darbe and placebo) in a 1:1 ratio. The primary hypothesis will evaluate whether infants receiving Darbe have higher cognitive scores at 22-26 months follow up, using a two-tailed test with 5% type 1 error and 90% power. Secondary outcomes that will be followed include: hematocrit, red cell mass, number and volume of transfusions, donor exposures, hospital days, and differences in morbidities (thromboses, hypertension, seizures, iCH, neC requiring surgery, BPD, RoP requiring intervention, culture positive sepsis); nDi, death, nDi or death, and CP at 22-26 months.