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Comparative Study
. 2024 Sep;68(8):1107-1119.
doi: 10.1111/aas.14441. Epub 2024 May 20.

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

Anders Granholm  1   2 , Marie Warrer Munch  1   2 , Nick Meier  1   2 , Fredrik Sjövall  3   4 , Marie Helleberg  5   6   7 , Frederik Boëtius Hertz  8   9 , Benjamin Skov Kaas-Hansen  1   2   10 , Hans-Christian Thorsen-Meyer  1   2 , Lars Wiuff Andersen  11   12   13 , Bodil Steen Rasmussen  2   14   15 , Jakob Steen Andersen  1 , Trine Lynge Albertsen  16 , Maj-Brit Nørregaard Kjær  1   2 , Aksel Karl Georg Jensen  10 , Theis Lange  10 , Anders Perner  1   2   5 , Morten Hylander Møller  1   2   5
Affiliations
Comparative Study

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

Anders Granholm et al. Acta Anaesthesiol Scand. 2024 Sep.

Abstract

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.

Keywords: adaptive clinical trial; carbapenems; empirical antibiotics; meropenem; piperacillin/tazobactam; randomised clinical trial; sepsis; septic shock.

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References

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