Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.
Acta Anaesthesiol Scand. 2024 Sep;68(8):1107-1119. doi: 10.1111/aas.14441. Epub 2024 May 20.
Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low.
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.
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.
在患有严重细菌感染的患者中，比阿培南/他唑巴坦与较差的结局相关，但其证据确定性低。
经验性美罗培南与哌拉西林/他唑巴坦治疗成人脓毒症患者（EMPRESS）试验是一项由研究者发起的、国际、平行组、随机、开放标签、适应性临床试验，具有集成可行性阶段。我们将随机分配成年、危重病患者接受经验性治疗，用美罗培南或哌拉西林/他唑巴坦治疗，时间长达 30 天。主要结局为 30 天全因死亡率。次要结局为 30 天内的严重不良反应；30 天内因耐药菌而采取隔离预防措施；30 天和 90 天内无生命支持和存活出院天数；30、90 和 180 天全因死亡率和 180 天健康相关生活质量。EMPRESS 将使用贝叶斯统计模型，带有弱到适度怀疑的中性先验。在对前 400 名参与者的主要结局进行随访后，以及每 300 名后续参与者后，将进行适应性分析，用于优势/劣势和实际等效性（绝对风险差异<2.5 个百分点）和反应适应性随机化的适应性停止。在无差异、小差异或大差异情况下的预期样本量分别为 5189、5859 和 2570 名参与者，最大样本量为 14000 名参与者，在所有情况下均有≥99%的结论可能性。
EMPRESS 将比较经验性美罗培南与哌拉西林/他唑巴坦在成人、危重病脓毒症患者中的疗效。由于具有高结论可能性的实用、适应性设计，试验结果有望直接为临床实践提供信息。
