Dept of Intensive Care, Erasme Hospital, Université libre de Bruxelles , Brussels , Belgium.
Department of Anesthesiology and Intensive Care, Uniklinikum Jena , Jena , Germany.
Expert Rev Clin Pharmacol. 2019 Sep;12(9):893-900. doi: 10.1080/17512433.2019.1643235. Epub 2019 Jul 22.
: Despite considerable advances in our understanding of how sepsis develops and multiple clinical trials of potential therapies, no new pharmacologic agent has been consistently shown to improve survival. : We reviewed relevant publications identified through PubMed and from the authors' knowledge of this field. We discuss the main reasons why clinical trials on new therapeutic interventions have failed in the past, including heterogeneity of study populations and choice of outcome measures. We discuss how changes in study design and in patient selection could help improve identification of effective agents in the future. : The search for new sepsis therapies must continue but lessons must be learned from previous clinical trials so that the same mistakes are not repeated. Rather than grouping all patients with sepsis together, we should study only those most likely to benefit from the intervention. Better characterization of patients will be facilitated using modern 'omics technology and analysis of the increasingly large quantities of clinical data available, enabling more personalized patient selection for trial inclusion. New clinical trial design and inclusion of other endpoints in addition to mortality will also aid our search for the elusive positive clinical trial and effective interventions for sepsis.
尽管我们对脓毒症的发病机制有了相当大的了解，并且进行了多次潜在治疗方法的临床试验，但没有一种新的药物被证明能持续改善存活率。我们回顾了通过 PubMed 以及作者对该领域知识的了解确定的相关出版物。我们讨论了过去新治疗干预临床试验失败的主要原因，包括研究人群的异质性和结局测量的选择。我们讨论了如何改变研究设计和患者选择，以帮助未来更好地确定有效药物。寻找新的脓毒症治疗方法必须继续，但必须从以前的临床试验中吸取教训，以免重蹈覆辙。我们不应该将所有脓毒症患者都归为一组，而应该只研究那些最有可能从干预中获益的患者。利用现代“组学”技术和分析越来越多的临床数据，可以更好地对患者进行特征描述，从而更有针对性地选择患者进行临床试验纳入。新的临床试验设计和除死亡率以外的其他终点的纳入也将有助于我们寻找难以捉摸的阳性临床试验和脓毒症的有效干预措施。
