早産児における輸血減少、鉄状態および神経発達改善のためのダルベポエチンと徐放性静脈内鉄の使用（DIVI）：無作為化、盲検化第II相試験の試験プロトコル

Infants born preterm are at high risk of anemia, red blood cell transfusions, and iron deficiency, all of which may negatively influence long-term neurodevelopment. To ameliorate these complications of prematurity, we developed a Phase II trial to determine whether treatment with an erythropoietic-stimulating agent, darbepoetin (Darbe), plus a slow-release intravenous (IV) iron preparation (ferumoxytol (FMX) or low-molecular-weight iron dextran (LMW-ID)) might decrease transfusions while maintaining iron sufficiency.

This single-center study is a parallel design, prospective, randomized controlled Phase II trial of 120 infants born 24-0/7 to 31-6/7 weeks of gestation cared for in the University of Washington Neonatal Intensive Care Unit. After informed consent, infants less than 72 h of age are randomized to one of five treatment groups: (1) Oral iron (standard care), n = 40, or weekly Darbe 10 µg/kg/dose IV or SQ plus; (2) FMX - 10 mg/kg/dose IV, n = 20; (3) FMX - 20 mg/kg/dose IV, n = 20; (4) LMW-ID - 10 mg/kg/dose IV, n = 20; or (5) LMW-ID - 20 mg/kg/dose IV, n = 20. Infants will be followed to 2-year corrected age with sequential developmental testing. Our primary outcome is ferritin level at 34-36 weeks postmenstrual age. Secondary outcomes include other hematologic assessments, drug safety, evaluation of the gut microbiome, and neurodevelopment to 2 years corrected age.

This trial will determine whether darbepoetin plus a slow-release IV iron preparation is safe, which iron preparation and dose best maintain iron sufficiency and decrease or eliminate transfusions, whether IV iron will result in a more diverse, less pathogenic microbiome when compared to oral iron supplementation, and, finally, whether these treatments affect neurodevelopment to 2 years corrected age.

National Clinical Trial (NCT) NCT05340465. Registered on March 1, 2022.