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首页> 外文期刊>Critical care : >Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis.
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Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis.

机译：在严重败血症患者中，drotrecogin alfa（激活）的ADDRESS和PROWESS研究中，登记顺序对观察结果的影响。

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ABSTRACT: INTRODUCTION: To determine whether an enrollment sequence effect noted in the PROWESS (the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial exists in the ADDRESS (the Administration of Drotrecogin Alfa (Activated) [DrotAA] in Early Stage Severe Sepsis) trial. METHODS: Evaluate prospectively defined subgroups from two large Phase 3 clinical trials. ADDRESS: 516 sites in 34 countries; PROWESS: 164 sites in 11 countries. ADDRESS: Patients with severe sepsis at low risk of death not indicated for treatment with DrotAA. PROWESS: Patients with severe sepsis with one or more organ dysfunctions. DrotAA (24 ug/kg/h) or placebo infused for 96 hours. RESULTS: In ADDRESS and PROWESS, there was a statistically significant interaction between the DrotAA treatment effect and the sequence in which patients were enrolled. In both trials, higher mortality was associated with DrotAA use in the subgroup of patients enrolled first at study sites. Compared with placebo, PROWESS mortality was lower with DrotAA treatment for the second and subsequent patients enrolled, while in ADDRESS, mortality remained higher for the second patient enrolled, but thereafter was lower for DrotAA-treated patients. Comparison of patients enrolled first with subsequent patients enrolled indicated the characteristics of patients changed. Subsequently enrolled patients were treated earlier, were less likely to suffer non-serious bleeds (ADDRESS), and experienced fewer protocol violations (PROWESS). CONCLUSIONS: Analyses suggest an enrollment sequence effect was present in the ADDRESS and PROWESS trials. Analysis of this effect on outcomes suggests it is most apparent in patients at lower risk of death. In PROWESS, this effect appeared to be associated with a reduction of the DrotAA treatment effect for the first patients enrolled at each site. In ADDRESS, this effect may have contributed to early termination of the study. The finding of an enrollment sequence effect in two separate trials suggests that trial designs, site selection and training, data collection and monitoring, and statistical analysis plans may need to be adjusted for these potentially confounding events. ADDRESS trial registration number: NCT00568737 PROWESS was completed before trial registration was required.
机译：摘要：简介：为了确定ADDRESS（早期严重脓毒症的Drotrecogin Alfa（已激活）[DrotAA]的使用）在ADDRESS（严重败血症中的重组人类活化蛋白C全球评估）试验中是否存在登记序列效应）试用。方法：评估两项大型3期临床试验的前瞻性定义的亚组。地址：34个国家/地区的516个站点;程序：在11个国家/地区的164个站点。地址：严重败血症，低死亡风险的患者未建议接受DrotAA治疗。病情：严重脓毒症的患者患有一种或多种器官功能障碍。 DrotAA（24 ug / kg / h）或安慰剂注入96小时。结果：在地址和过程中，DrotAA治疗效果与患者入组顺序之间存在统计学上的显着相互作用。在这两项试验中，较高的死亡率与在研究地点首次入组的患者亚组中使用DrotAA有关。与安慰剂相比，接受DrotAA治疗的第二位及以后患者的PROWESS死亡率较低，而接受ADDRESS治疗的第二位患者和第二位患者的死亡率仍然较高，但随后接受DrotAA治疗的患者死亡率更低。比较首次入组的患者和随后入组的患者，表明患者特征发生了变化。随后入组的患者接受了更早的治疗，不太可能遭受非严重出血（ADDRESS），并且经历了更少的违反协议的行为（PROWESS）。结论：分析表明在ADDRESS和PROWESS试验中存在入组序列效应。对结果影响的分析表明，它在死亡风险较低的患者中最为明显。在PROWESS中，对于在每个部位入组的首批患者，该效应似乎与DrotAA治疗效果的降低有关。在ADDRESS中，这种影响可能有助于提前终止研究。在两个单独的试验中发现入组顺序效应表明，可能需要针对这些潜在的混杂事件调整试验设计，选址和培训，数据收集和监测以及统计分析计划。地址试用注册号：NCT00568737 PROWESS已完成，需要进行试用注册。

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