Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial: Protocol
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Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial : Protocol. / Granholm, Anders; Munch, Marie Warrer; Meier, Nick; Sjövall, Fredrik; Helleberg, Marie; Hertz, Frederik Boëtius; Kaas-Hansen, Benjamin Skov; Thorsen-Meyer, Hans Christian; Andersen, Lars Wiuff; Rasmussen, Bodil Steen; Andersen, Jakob Steen; Albertsen, Trine Lynge; Kjær, Maj Brit Nørregaard; Jensen, Aksel Karl Georg; Lange, Theis; Perner, Anders; Møller, Morten Hylander.
In: Acta Anaesthesiologica Scandinavica, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial
T2 - Protocol
AU - Granholm, Anders
AU - Munch, Marie Warrer
AU - Meier, Nick
AU - Sjövall, Fredrik
AU - Helleberg, Marie
AU - Hertz, Frederik Boëtius
AU - Kaas-Hansen, Benjamin Skov
AU - Thorsen-Meyer, Hans Christian
AU - Andersen, Lars Wiuff
AU - Rasmussen, Bodil Steen
AU - Andersen, Jakob Steen
AU - Albertsen, Trine Lynge
AU - Kjær, Maj Brit Nørregaard
AU - Jensen, Aksel Karl Georg
AU - Lange, Theis
AU - Perner, Anders
AU - Møller, Morten Hylander
N1 - Publisher Copyright: © 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - adaptive clinical trial
KW - carbapenems
KW - empirical antibiotics
KW - meropenem
KW - piperacillin/tazobactam
KW - randomised clinical trial
KW - sepsis
KW - septic shock
U2 - 10.1111/aas.14441
DO - 10.1111/aas.14441
M3 - Journal article
C2 - 38769040
AN - SCOPUS:85193628392
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
SN - 0001-5172
ER -
ID: 393044813