Procalcitonin-guided decision and antibiotic treatment duration in late onset sepsis of newborns: multicentre, randomised controlled trial (ProABIS).

Objective: To assess whether procalcitonin-guided decision making can safely reduce the duration of antibiotic treatment in neonatal late onset sepsis. Design: Prospective multicentre, randomised open label trial. Setting: 33 level 3 and level 2B neonatology departments in France. Participants: Newborn babies born after 24 weeks' gestation, of postconceptional age 24-45 weeks and after 4 days of life, weighing more than 700 g, with suspected or proven late onset sepsis, requiring antibiotics for more than 48 hours, and without meningitis, septic shock, and deep-seated infection. Interventions: Participants were randomly assigned to procalcitonin-guided or usual care antibiotic treatment. In the procalcitonin-guided group, procalcitonin concentration was measured at randomisation and then every two days. A non-binding recommendation to discontinue antibiotics was given if the procalcitonin concentration was 0.5 µg/L or lower. In the usual care group, treatment was provided according to local protocols. Main outcome measures: The primary outcome was the duration of antibiotic treatment (under the superiority hypothesis). The key secondary outcome was non-inferiority for mortality (margin 3%) at day 28 after randomisation. Results: Between February 2019 and February 2023, 248 newborns were randomised to the procalcitonin-guided group and 256 to the usual care group. In the intention-to-treat analysis, the median duration of antibiotic treatment was eight days (interquartile range (IQR) 5.0-12.0) in the procalcitonin-guided group versus 10 days (8.0-13.0) in the usual care group (absolute difference between groups -2.0 (IQR -3.8 to -1.0), P<0.001). At day 28, the proportion of death was six of 248 newborns (2.4%) in the procalcitonin-guided group versus 10 of 256 (3.9%) in the usual care group (absolute difference between groups -1.5% (95% confidence interval (CI) -5.0 to 1.8). The proportion of recurrence was seven of 248 (2.8%) newborns in the procalcitonin-guided group versus 10 (3.9%) of 256 in the usual care group (absolute difference between groups -1.1% (95% CI -4.6 to 2.3). Conclusion: In this study population, the use of procalcitonin significantly reduced the duration of antibiotic treatment in neonatal late onset sepsis, without increasing mortality or serious adverse events. Trial registration: NCT03730636.