Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial: Protocol.

Autor: Granholm A; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark., Munch MW; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark., Meier N; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark., Sjövall F; Department of Intensive and Perioperative Care, Skåne University Hospital, Malmö, Sweden.; Department of Clinical Sciences, Lund University, Lund, Sweden., Helleberg M; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Centre of Excellence for Health, Immunity and Infections, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark., Hertz FB; Department of Clinical Microbiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark., Kaas-Hansen BS; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Thorsen-Meyer HC; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark., Andersen LW; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.; Prehospital Emergency Medical Services, Aarhus, Denmark., Rasmussen BS; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.; Department of Anaesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark.; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark., Andersen JS; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark., Albertsen TL; Sentinel Unit, Sundhed.dk, Odense, Denmark., Kjær MN; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark., Jensen AKG; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Lange T; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Perner A; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Møller MH; Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Acta anaesthesiologica Scandinavica [Acta Anaesthesiol Scand] 2024 Sep; Vol. 68 (8), pp. 1107-1119. Date of Electronic Publication: 2024 May 20.
DOI: 10.1111/aas.14441
Abstrakt: Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low.
Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios.
Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
(© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)
Databáze: MEDLINE
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