RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
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DOI：
10.1001/jama.271.23.1836
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发表时间：
1994-06-15
影响因子：
120.7
通讯作者：
STABLEIN, D
中科院分区：
文献类型：
--
作者：
FISHER, CJ;DHAINAUT, JFA;STABLEIN, D
客观。-进一步明确重组人白细胞介素1受体拮抗剂（rhIL-1 ra）治疗脓毒症综合征的安全性和有效性。随机、双盲、安慰剂对照、多中心、多国临床试验。共有893例脓毒症患者接受了rhIL-1 ra 100 mg或安慰剂的静脉负荷剂量，随后连续72小时静脉输注rhIL-1 ra（每小时1.0或2.0 mg/kg）或安慰剂。28天全因死亡率结果在所有接受研究药物治疗的患者（n=893;广义Wilcoxon统计量，P= 0.22）或在研究入组时发生休克的患者（n=713;广义Wilcoxon统计量，P= 0.23）中，与安慰剂相比，rhIL-1 ra治疗的生存时间没有显著增加，这两项主要疗效分析规定了本试验的先验性。二次分析结果表明，在一个或多个器官功能障碍患者中，rhIL-1 ra治疗可延长生存时间（n=563;线性剂量反应，P= 0.009）。回顾性分析表明，在预测死亡风险为24%或更高的患者中（n=580;线性剂量反应，P= 0.005），以及在一个或多个器官功能障碍和预测死亡风险为24%或更高的患者中（n=411;线性剂量反应，P= 0.002），rhIL-1 ra治疗的生存时间增加。在所有接受研究药物治疗的患者或进入研究时发生休克的患者中，与安慰剂相比，rhIL-1 ra治疗的生存时间没有统计学显著增加。疗效的次要和回顾性分析表明，在有器官功能障碍和/或预测死亡率风险为24%或更高的脓毒症患者中，rhIL-1 ra治疗可导致剂量相关的生存时间延长。
Objective.-To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhlL-1ra) in the treatment of sepsis syndrome.Study Design.-Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial.Population.-A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo.Outcome Measure.-Twenty-eight-day all-cause mortality.Results.-There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n=893; generalized Wilcoxon statistic, P=.22) or among patients with shock at study entry (n=713; generalized Wilcoxon statistic, P=.23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n=563; linear dose-response, P=.009). Retrospective analysis demonstrated an increase In survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n=580; linear dose-response, P=.005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n=411; linear dose-response, P=.002).Conclusions.-There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.