Pentoxifylline Effects on Late-Onset Sepsis in Preterm Neonates: A Pilot Randomized Clinical Trial

Background: Despite the progress in the management of late-onset sepsis (LOS), it is the leading cause of mortality in preterm infants worldwide. Pentoxifylline is a methylxanthine with well-documented immunomodulatory properties, which may be an important approach to treating LOS.This study aimed to evaluate the efficacy and safety of adding oral pentoxifylline standard care among preterm neonates with LOS. Methods: In this trial, 47 preterm neonates with a confirmed diagnosis of LOS were allocated to either receive Pentoxifylline 10 mg/kg three times a day orally plus standard care (n=23) or the standard care alone for 6 days (n=24) using the block randomization method. The primary outcomes were the duration of C-reactive protein (CRP) negativity, duration of supplemental oxygen therapy, hospitalization and mortality rate. Secondary outcomes included the assessment of any adverse events that may have occurred during the study. Continuous data were analyzed using the independent t-test or Mann–Whitney U test. Chi-square and/or Fisher’s exact tests are used for categorical variables. The logistic regression analysis was also used for comparing mortality after adjusting for covariates. Results: The demographic characteristics, mothers/infants-related risk factors, use of antenatal steroids, neonatal resuscitation, antibiotic regimen, and surfactant administration were statistically similar between the intervention and control groups; however, respiratory support significantly differed. After adjusting for respiratory support, there was no significant difference regarding the duration of hospitalization (P=0.56), CRP negativity (P=0.69), supplemental oxygen therapy (P=0.94), and mortality rate (P=0.5) between the study groups. Conclusion: Adding oral pentoxifylline to standard care had no significant benefits on clinical and paraclinical outcomes in preterm neonates with LOS. Further clinical trials are needed to test the study hypothesis.