Lyseng-Williamson Katherine A, Perry Caroline M
Adis International Limited, Auckland, New Zealand.
Drugs. 2002;62(4):617-30; discussion 631-2. doi: 10.2165/00003495-200262040-00006.
Drotrecogin alfa (activated), recombinant human activated protein C, inhibits coagulation and inflammation and promotes fibrinolysis in patients with severe sepsis. 850 patients with severe sepsis treated with intravenous drotrecogin alfa (activated) 24 microg/kg/h for 96 hours had a significantly greater reduction in 28-day all-cause mortality (24.7%) than 840 placebo recipients (30.8%) in a randomised, double-blind, placebo-controlled study. The drug was associated with a 19.4% reduction in the relative risk of death at 28 days compared with placebo. Baseline characteristics of and pre-existing conditions in patients with sepsis appeared to have no effect on the efficacy of drotrecogin alfa (activated). A significantly greater reduction in median percentage change from baseline plasma D-dimer levels (a coagulation marker) was seen with drotrecogin alfa (activated) treatment than with placebo on study days 1 to 7 in patients with severe sepsis. On study days 1, 4, 5, 6 and 7, a significantly greater median reduction in interleukin-6 levels (an inflammation marker) from baseline was seen with drotrecogin alfa (activated) treatment than placebo. Drotrecogin alfa (activated) was associated with an increased incidence of serious bleeding events during the infusion period [2.4% vs 1.0% with placebo; p = 0.024] and the 28-day study period (3.5 vs 2.0%; p = 0.06) of the efficacy trial. This increase was primarily related to procedure-related events; there were no significant differences between the treatment groups in nonprocedure-related serious bleeding events. The most frequent site of bleeding was the gastrointestinal tract. With the exception of bleeding events, there were no clinically significant differences between treatment groups in the efficacy trial in the incidence of adverse events. Of the 210 deaths in patients with severe sepsis treated with drotrecogin alfa (activated) 24 microg/kg/h in the efficacy trial, four deaths due to haemorrhage and one due to cerebral oedema were possibly related to the study drug.
重组人活化蛋白C——活化蛋白C，可抑制重症脓毒症患者的凝血与炎症反应，并促进纤溶。在一项随机、双盲、安慰剂对照研究中，850例接受静脉注射活化蛋白C（剂量为24微克/千克/小时，持续96小时）治疗的重症脓毒症患者28天全因死亡率（24.7%）较840例接受安慰剂治疗的患者（30.8%）显著降低。与安慰剂相比，该药物使28天死亡相对风险降低了19.4%。脓毒症患者的基线特征和既往病情似乎对活化蛋白C的疗效没有影响。在重症脓毒症患者中，与安慰剂相比，在研究第1至7天，活化蛋白C治疗使血浆D - 二聚体水平（一种凝血标志物）自基线的中位百分比变化显著降低。在研究第1、4、5、6和7天，与安慰剂相比，活化蛋白C治疗使白细胞介素 - 6水平（一种炎症标志物）自基线的中位降低幅度显著更大。在疗效试验的输注期[2.4% 对比安慰剂组的1.0%；p = 0.024]以及28天研究期（3.5%对比2.0%；p = 0.06），活化蛋白C与严重出血事件发生率增加相关。这种增加主要与操作相关事件有关；在非操作相关的严重出血事件方面，治疗组之间无显著差异。最常见的出血部位是胃肠道。除出血事件外，在疗效试验中，治疗组之间不良事件发生率无临床显著差异。在疗效试验中，接受24微克/千克/小时活化蛋白C治疗的210例重症脓毒症患者死亡病例中，4例因出血死亡，1例因脑水肿死亡可能与研究药物有关。
