Abstract
ABSTRACT
Background
Meropenem and piperacillin/tazobactam are commonly used empirical antibiotics in critically ill adults with sepsis, but whether one is superior to the other is uncertain.
Methods
The
Empirical Meropenem
versus
Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS)
trial is an ongoing investigator‐initiated, randomised, open‐label, adaptive clinical trial with an integrated feasibility phase comparing empirical treatment with meropenem versus piperacillin/tazobactam in critically ill adults with sepsis. The integrated feasibility phase enrolled 200 participants across 10 intensive care units (ICUs) in Denmark between 28 June and 12 December 2025. Five pre‐specified feasibility criteria were evaluated; if all feasibility criteria were met, the trial would proceed unaltered, whereas failure to meet one or more criteria would require intervention and re‐evaluation.
Results
We randomised 200 of 284 screened patients (70.4%). The median age was 70 years (interquartile range (IQR): 60–77), 65.5% were males. At randomisation, 80.0% received vasopressors or inotropes, and 43.5% were on invasive mechanical ventilation. Four of five pre‐specified feasibility criteria were met: time to completion of the feasibility phase (5.5 months vs. threshold
Conclusions
In this integrated feasibility evaluation of the
EMPRESS
trial comparing empirical meropenem versus piperacillin/tazobactam in critically ill adults with sepsis, four of five pre‐specified feasibility criteria were met. The unmet criterion, timely primary outcome data availability, improved substantially during the feasibility phase. We consider the trial feasible and will proceed without modifications.
Editorial Comment
This feasibility study assessed recruitment, randomised allocation and data collection for the multicentre EMPRESS trial. For adaptive trials on trial platforms, careful interim checking of trial design functions is an important and necessary process.
Trial Registration:
Clinical Trials Information System EUCT number: 2023‐509703‐33‐00; ClinicalTrials.gov identifier: NCT06184659; Universal Trial Number: U1111‐1301‐6379