• Anders Granholm, Marie Warrer Munch, Nick Meier, Fredrik Sjövall, Marie Helleberg, Frederik Boëtius Hertz, Benjamin Skov Kaas-Hansen, Hans-Christian Thorsen-Meyer, Lars Wiuff Andersen, Bodil Steen Rasmussen, Jakob Steen Andersen, Trine Lynge Albertsen, Maj-Brit Nørregaard Kjær, Aksel Karl Georg Jensen, Theis Lange, Anders Perner, and MøllerMorten HylanderMHDepartment 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, U.
• Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
• Acta Anaesthesiol Scand. 2024 Sep 1; 68 (8): 110711191107-1119.

BackgroundPiperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low.MethodsThe 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.ConclusionsEMPRESS 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.

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