title: Erythropoietin neuroprotection in neonatal cardiac surgery: a phase I/II safety and efficacy trial.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, Houston, Tex 77030, USA. dra@bcm.tmc.edu
authors.forename: Dean B
authors.initials: DB
authors.lastname: Andropoulos
authors.forename: Ken
authors.initials: K
authors.lastname: Brady
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Easley
authors.forename: Heather A
authors.initials: HA
authors.lastname: Dickerson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Voigt
authors.forename: Lara S
authors.initials: LS
authors.lastname: Shekerdemian
authors.forename: Marcie R
authors.initials: MR
authors.lastname: Meador
authors.forename: Carol A
authors.initials: CA
authors.lastname: Eisenman
authors.forename: Jill V
authors.initials: JV
authors.lastname: Hunter
authors.forename: Marie
authors.initials: M
authors.lastname: Turcich
authors.forename: Carlos
authors.initials: C
authors.lastname: Rivera
authors.forename: Emmett D
authors.initials: ED
authors.lastname: McKenzie
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Heinle
authors.forename: Charles D
authors.initials: CD
authors.lastname: Fraser
mesh_terms: D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D004921:Erythropoietin / Q000627:therapeutic use*; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011446:Prospective Studies; D016037:Single-Blind Method
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin