Efficacy of the Granulocyte Colony-Stimulating Factor in Sepsis-Associated Immunosuppression: An Open-Label Randomized Controlled Trial.

objectiveTo determine the efficacy of filgrastim (G-CSF) in reducing the mortality in children with multi-organ failure syndrome (MOFS) persisting for three consecutive days.  Methods: Children aged 1 month to 18 years with two or more organ failures persisting for three days according to Goldstein's criterion were included and randomized to receive either standard of care and filgrastim (G-CSF) at a dose of 4 mcg/kg/day subcutaneously for seven days or standard of care at a 1:1 ratio. The stored blood samples were estimated for TNF-α, A Disintegrin and Metalloproteinase Motifs 13 (ADAMTS13), and soluble Fas ligand (FasL) at the end of the study to confirm the biomarker-based inflammatory phenotypes of sepsis-induced MOFS. Outcomes were 28-day mortality and differences in tumor necrosis factor-alpha (TNF-α) levels, hospital-acquired infection (HAI), and pediatric sequential organ failure assessment score (pSOFA) at seven days of randomization.

resultsOf 78 children, 25 (32%), 50 (64.1%), and 3 (3.8%) were discharged, died, and left against medical advice (LAMA), respectively. The two groups were similar except for a higher TLC (14100 [11400-16270]) vs. (17560 [13900-22100]; p=0.02) and male preponderance (18/39 vs. 27/39; p=0.03) in the control group. The intervention group received 2 (2-3) median (IQR) doses of filgrastim (G-CSF) for a 3 (2-3) median (IQR) duration of days. No significant difference was observed between the groups regarding 28-day mortality (26/39 vs. 27/39; 95% CI, p (0.71-1.31, p=0.81), HAI (31/62 vs. 21/53; p=0.27). The pSOFA scores and TNF-α levels at seven days were 8 (6-12) vs. 9 (8-11) (p=0.12) and 81.6 (6.9-237.2) vs. 99.6 (16.2-404.2) (p=0.29), respectively. Subgroup analysis revealed a similar occurrence of mortality in immunoparalysis-associated multi-organ failure (IPMOF) (16/26 vs. 14/21); 95% CI, p (0.60-1.42, p=0.71) at 28 days, and 2 median dose of filgrastim (G-CSF) for 3 median day did not significantly change the TNF-α levels within the intervention group at day seven (56 [32-118] vs. 19 [6.9-118], p=0.77) as compared to day 0. We did not observe any life-threatening/significant sudden deterioration/anaphylaxis after use of filgrastim (G-CSF).

conclusionsFilgrastim (G-CSF) use in immunocompetent children with sepsis-induced MOFS is safe, and a 2-dose of filgrastim (G-CSF) for three days has poor efficacy in the reduction of mortality and did not show significant change in frequency of HAI, TNF-α levels, and pSOFA scores.