Pentoxifylline dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

The aim of this study (PTX-trial) is to determine the optimal dose of pentoxifylline (PTX) in preterm neonates (gestational age < 30 weeks) with (suspected) late onset sepsis (LONS).

The PTX-trial is a prospective multicentre open-label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design was used, with dose step-up and step-down titration per three patients with a PTX dose of 30 mg/kg/day in 6 h for 3 days in the first group. The primary outcome was an ED75, which was defined as a both clinical and chemical effective dose for 75% of preterm neonates with LONS.

In total, 30 neonates were included in the study. As an effective dose was only observed in 27% of the patients, the ED75 could not be determined. There were no significant differences in biochemical and clinical response between the different dosage groups. The largest decrease in nSOFA score after start of PTX was observed in the dosage group of 30 mg/kg/day in 6 h.

In this dose-finding trial for PTX in preterm neonates, our findings reveal no discernible clinical advantage associated with either increasing or decreasing the PTX dosage. The relatively high variability in sepsis severity and patients' post-natal ages increase the uncertainty of our findings, but the standardly used dosage of 30 mg/kg/day (5 mg/kg/h for 6 h) has consistently demonstrated safe tolerability without any reported severe adverse events.