Cobas Meyer M, Langenfeld H, Rossaint R, Sablotzki A
Medizinische Abteilung, Lilly Critical Care Europe, Bad Homburg.
Anaesthesist. 2006 Jun;55 Suppl 1:16-23. doi: 10.1007/s00101-006-1028-1.
Drotrecogin alfa (activated) (DrotAA) represents a therapeutic advance in the treatment of severe sepsis. In the pivotal PROWESS trial DrotAA had demonstrated a significant decrease in 28-day mortality, most evident in the subgroup of patients at higher risk of death. Thus, DrotAA was licensed throughout Europe for treatment of adult patients with severe sepsis with multiple organ failure when added to best standard care. The ADDRESS trial was mandated by the FDA to investigate prospectively the treatment effect of DrotAA in patients at low risk of death, e.g. single organ failure. The trial was prematurely stopped due to futility, because no reduction in mortality was observed in this non-indicated patient population. The ENHANCE open-label trial enrolled similar patients to the PROWESS trial and the observed 28-day mortality was consistent with the results seen in the PROWESS trial. Survival rates for patients receiving DrotAA early within 24 h from the first sepsis-induced organ dysfunction were significantly higher than in patients treated later. In this overview we will discuss the results of the ENHANCE and ADDRESS trials in the context of the PROWESS study and clinical implications for the treatment with DrotAA.
活化蛋白C（Drotrecogin alfa activated，DrotAA）是严重脓毒症治疗领域的一项治疗进展。在关键的PROWESS试验中，DrotAA已证明28天死亡率显著降低，这在死亡风险较高的患者亚组中最为明显。因此，在欧洲，当添加到最佳标准治疗中时，DrotAA被批准用于治疗患有严重脓毒症并伴有多器官功能衰竭的成年患者。FDA要求进行ADDRESS试验，以前瞻性地研究DrotAA对死亡风险较低的患者（如单器官功能衰竭患者）的治疗效果。该试验因无效而提前终止，因为在这个未指明的患者群体中未观察到死亡率降低。ENHANCE开放标签试验纳入了与PROWESS试验相似的患者，观察到的28天死亡率与PROWESS试验的结果一致。在首次出现脓毒症诱导的器官功能障碍后24小时内尽早接受DrotAA治疗的患者生存率显著高于较晚接受治疗的患者。在本综述中，我们将结合PROWESS研究讨论ENHANCE和ADDRESS试验的结果以及DrotAA治疗的临床意义。
