Рандомизированное двойное слепое плацебо-контролируемое исследование применения рекомбинантного гранулоцитного колоний-стимулирующего фактора у недоношенных новорожденных с клиническим диагнозом раннего сепсиса

A Randomized, Double-Masked, Placebo-Controlled Trial of Recombinant Granulocyte Colony-Stimulating Factor Administration to Preterm Infants With the Clinical Diagnosis of Early-Onset Sepsis

Ernani Miura, Renato S. Procianoy, Cristina Bittar, Clarissa S. Miura, Mauricio S. Miura, Cintia Mello, and Robert D. Christensen

From the Department of Pediatrics, Division of Neonatology, Hospital de Clinicas de Porto Alegre, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; and the Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Gainesville, Florida

Objective. We performed a randomized, double-masked, parallel-groups, placebo-controlled trial of recombinant granulocyte colony-stimulating factor (rG-CSF) administration to 44 preterm neonates who had blood cultures obtained and antibiotics begun because of the clinical diagnosis of early-onset sepsis. Two primary outcome variables were tested 1) mortality and 2) development of nosocomial infections over the 2-week period after dosing. Design and Methods. The treatment group (n = 22) received 10 µg/kg/day of intravenous rG-CSF once daily for 3 days and the placebo group (n = 22) received the same volume of a visually indistinguishable vehicle. Mortality and culture-proven nosocomial infections were recorded. Immediately before the first, second, and third doses, and again 10 days after the first dose, serum concentrations were determined for tumor necrosis factor-, interleukin 6, granulocyte-macrophage colony stimulating factor, and G-CSF, and blood leukocyte counts, absolute neutrophil counts, immature/total neutrophil 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 Physiology scores. The mortality rate was not different between treatment and placebo groups. However, the occurrence of a subsequent nosocomial infection was lower in the rG-CSF recipients (relative risk: .19; 95% confidence interval: .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 neutrophil counts were higher in the treatment than in the placebo group 24 hours and 48 hours after dosing. Conclusions. Administration of 3 daily doses of rG-CSF (10 µg/kg/day) to premature neonates with the clinical diagnosis of early-onset sepsis did not improve mortality but was associated with acquiring fewer nosocomial infections over the subsequent 2 weeks.

Pediatrics 2001;107 30-35