Antithrombin III in patients with severe sepsis - A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis
Antithrombin III in patients with severe sepsis - A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis
复制标题
DOI：
10.1007/s001340050642
复制
发表时间：
1998-07-01
影响因子：
38.9
通讯作者：
Delvos, U
中科院分区：
文献类型：
--
作者：
Eisele, B;Lamy, M;Delvos, U
目的：评估抗凝血酶III（AT III）在降低严重脓毒症患者死亡率方面的安全性和潜在疗效。设计：前瞻性、随机、安慰剂对照、双盲、II期、多中心、多国临床试验。设置：比利时、丹麦、荷兰、挪威和瑞典的七个学术医疗中心重症监护室（ICU）。42例严重脓毒症患者接受标准的支持性治疗和抗菌治疗，除了管理AT III或placebo.Interventions：患者接受静脉内负荷剂量3000 IU AT III，然后维持剂量1500 IU每12小时5天或等量的安慰剂。测量和结果：所有患者的安全性和30天的全因mortals.Conclusions：AT III的管理是安全的，耐受性良好。随后30天全因死亡率（NS）降低了39%。死亡率的降低伴随着在ICU的停留时间大大缩短。接受AT III治疗的患者在疾病的总体严重程度和器官衰竭评分方面表现出更好的表现（急性生理学和慢性健康评估II？多器官衰竭，器官系统衰竭）？这在治疗开始后不久就很明显。在观察期间，接受AT III治疗的患者表现出既存器官衰竭的更好解决和新器官衰竭的发生率更低。一项荟萃分析包括本研究和另外两项双盲、安慰剂对照的AT III试验，共纳入122例严重脓毒症患者，证实了这一积极趋势。荟萃分析的结果表明，接受AT III治疗的患者30天全因死亡率降低了22.9%。虽然仍然太小，无法证实，但荟萃分析清楚地指出了一个事实，即有足够的把握度的III期试验是必要的，以证明AT III是否在治疗严重脓毒症中具有有益作用。
Objectives:To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis.Design: Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial.Setting: Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden.Patients. 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo.Interventions: Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo. Measurements and results: Ail patients were evaluated for safety and for 30-day all-cause mortality.Conclusions: The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II? multiple organ failure, organ system failure)? which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.