A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with theclinical diagnosis of early-onset sepsis

Objective. We performed a randomized, double-masked, parallel-groups, place bo-controlled trial of recombinant granulocyte colony-stimulating factor (r G-CSF) administration to 44 preterm neonates who had blood cultures obtaine d and antibiotics begun because of the clinical diagnosis of early-onset se psis. Two primary outcome variables were tested 1) mortality and 2) develop ment of nosocomial infections over the 2-week period after dosing. Design and Methods. The treatment group (n = 22) received 10 mug/kg/day of intravenous rG-CSF once daily for 3 days and the placebo group (n = 22) rec eived the same volume of a visually indistinguishable vehicle. Mortality an d culture-proven nosocomial infections were recorded. Immediately before th e first, second, and third doses, and again 10 days after the first dose, s erum concentrations were determined for tumor necrosis factor-alpha, interl eukin 6, granulocyte-macrophage colony stimulating factor, and G-CSF, and b lood leukocyte counts, absolute neutrophil counts, immature/total neutrophi l ratios, platelet counts, and hemoglobin concentrations were measured. Results. The treatment and placebo groups were of similar gestational age ( 29 +/- 3 vs 31 +/- 3 weeks) and birth weight (1376 +/- 491 vs 1404 +/- 508 g), and had similar Apgar scores and 24-hour Score for Neonatal Acute Physi ology scores. The mortality rate was not different between treatment and pl acebo groups. However, the occurrence of a subsequent nosocomial infection was lower in the rG-CSF recipients (relative risk: .19; 95% confidence inte rval: .05-.78). rG-CSF treatment did not alter the serum concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels and blood neu trophil counts were higher in the treatment than in the placebo group 24 ho urs and 48 hours after dosing. Conclusions. Administration of 3 daily doses of rG-CSF (10 mug/kg/day) to p remature neonates with the clinical diagnosis of early-onset sepsis did not improve mortality but was associated with acquiring fewer nosocomial infec tions over the subsequent 2 weeks.