Erythropoietin neuroprotection in neonatal cardiac surgery: a phase I/II safety and efficacy trial.

OBJECTIVES: Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems. Erythropoietin has antiapoptotic, antiexcitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy. METHODS: Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin or placebo. Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months. RESULTS: Fifty-nine patients received the study drug. Safety profile, including magnetic resonance imaging brain injury, clinical events, and death, was not different between groups. Three patients in each group died. Forty-two patients (22 in the erythropoietin group and 20 in the placebo group; 79% of survivors) returned for 12-month follow-up. In the group receiving erythropoietin, mean Cognitive Scale scores were 101.1 ± 13.6, Language Scale scores were 88.5 ± 12.8, and Motor Scale scores were 89.9 ± 12.3. In the group receiving placebo, Cognitive Scale scores were 106.3 ± 10.8 (P = .19), Language Scores were 92.4 ± 12.4 (P = .33), and Motor Scale scores were 92.6 ± 14.1 (P = .51). CONCLUSIONS: Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups; however, this pilot study was not powered to definitively address this outcome. Lessons learned suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population.