KInetics of Procalcitonin to Reduce Unnecessary aNtibiotic use (KIPRUN): protocol for a multicentre, randomised, superiority trial to compare the efficacy and safety of procalcitonin kinetics-guided and absolute procalcitonin value-guided antibiotic initiation in critically ill patients.

内容摘要

Appropriate antibiotic (AB) therapy remains a challenge in intensive care units (ICUs). Guidelines recommend against using procalcitonin (PCT) to guide the initiation of AB therapy, although with low certainty and a very low level of evidence. Recent studies suggest that changes in PCT levels may be more accurate than a single measurement; however, this has never been tested in a randomised trial. In this multicentre, randomised controlled trial (RCT), we aim to compare the efficacy and safety of two different PCT protocols for initiating AB therapy. Hemodynamically stable, critically ill adult patients with suspected new-onset infection at admission or during ICU stay will be randomised in a 1:1 ratio. In the treatment arm (Kinetics Group, KG), initiation of AB treatment is strongly recommended if PCT ≥0.5 ng/mL and increases by more than 100% compared with the previous day. In the control arm (Absolute Group, AG), the initiation of AB treatment is strongly recommended if PCT ≥0.5 ng/mL. The primary outcome will be the rate of unnecessary AB therapy: 72 hours after recruitment, an independent intensivist, microbiologist and infectologist will determine whether the therapy was necessary, using all relevant clinical, microbiological and radiographic results. If no consensus is reached, a decision will be made by secret vote. We plan to enrol 250 participants in the study, with 80% statistical power and a 5% alpha level. Ethics approval was obtained from the National Centre for Public Health and Pharmacy (BM/20019/2025). We plan to present our results at relevant national and international conferences and meetings and to submit them for publication in a peer-reviewed journal. Moreover, we plan to disseminate the results to important stakeholders in the Hungarian healthcare system. This is the first version of the trial protocol, prepared in accordance with the SPIRIT 2025 guideline (version 1.0, dated 30 September 2025). The trial has been registered on ClinicalTrials.gov (NCT07211620).