Sepsis Antibiotic Trial Feasibility

The EMPRESS integrated feasibility phase examined whether a larger trial comparing empirical meropenem with piperacillin/tazobactam could be conducted in critically ill adults with sepsis. It was not designed to establish which treatment is clinically superior. pmid:42674465

Evidence

Investigators conducted an investigator-initiated, randomized, open-label, adaptive clinical trial with an integrated feasibility phase in critically ill adults with sepsis in Denmark. The phase enrolled 200 participants, and the intervention comparison was empirical meropenem versus empirical piperacillin/tazobactam. pmid:42674465

The feasibility assessment evaluated recruitment, randomized allocation, and data collection after participants completed 30-day follow-up. Five pre-specified criteria guided the decision process. Blinding was not performed, and protocol adherence was assessed systematically from daily electronic case-report-form data, including administration of trial medication and use of other antibiotic agents. pmid:42674465

Four of five pre-specified feasibility criteria were met. The criterion for timely availability of the primary outcome, 30-day mortality, within 45 days was 85.5%, below its pre-specified threshold of at least 95.0%; the investigators reported that this measure reached 95.8% in the final month of the feasibility phase. pmid:42674465

The investigators considered the trial feasible and planned to proceed without modifications. This conclusion concerns the ability to recruit, randomize, collect outcome data, and implement the trial procedures; it does not establish whether meropenem or piperacillin/tazobactam produces better outcomes in critically ill adults with sepsis. pmid:42674465

Analysis — Feasibility signal

The central signal is operational rather than therapeutic. Randomization and protocol-delivery processes were implemented in the enrolled population, and the investigators judged that four satisfied feasibility criteria supported continuation without modification. The delayed primary-outcome-data criterion matters because adaptive trial decisions depend on timely data, yet the reported improvement during the feasibility phase suggests that the problem was monitored within the trial’s prespecified framework. That improvement should not be treated as a comparative clinical result or as proof that data timeliness will remain adequate in later trial conduct. pmid:42674465

The appropriate reading is therefore narrow: this work supports the practicality of proceeding with the EMPRESS trial, while the effectiveness question remains open. An open-label feasibility phase can inform how a larger randomized comparison is run, including recruitment, allocation, adherence monitoring, and outcome collection. It cannot by itself determine superiority between the two empirical antibiotic strategies, because the reported purpose and conclusions concern feasibility rather than a treatment-effect comparison. Statistical or operational success in feasibility criteria is also distinct from demonstrating a clinically meaningful benefit for either regimen. pmid:42674465

Limitations

The timely-primary-outcome-data criterion did not reach its pre-specified threshold during the feasibility phase, despite improvement in the final month. This is directly relevant to the reliability and speed of future adaptive analyses, because the trial specified timely data availability as one of its feasibility conditions. pmid:42674465

The study was open-label, with no blinding performed. In addition, the reported feasibility conclusion does not resolve the underlying uncertainty over whether carbapenems are superior to piperacillin/tazobactam in critically ill adults with sepsis. The findings should consequently be understood as preparation for a comparative efficacy trial rather than evidence of a treatment recommendation. pmid:42674465

Evidence boundary

This one-source briefing is limited to what the cited study reports. It does not establish independent confirmation, broader clinical effectiveness, or patient-specific guidance. The design, population, measurements, and follow-up described in that source define the evidence boundary. This summary provides research context and is not medical advice. The evidence should be read as a bounded report of the study rather than as a conclusion about other populations, settings, interventions, or outcomes. Any possible connection to disease mechanisms remains limited to the measurements and interpretations documented by the cited authors. Terms describing associations, responses, or biological patterns retain the meaning and uncertainty given in that source.

No inference beyond the cited source is made here.