Eisele B, Lamy M, Thijs L G, Keinecke H O, Schuster H P, Matthias F R, Fourrier F, Heinrichs H, Delvos U
Clinical Research Department, Centeon Pharma GmbH, Marburg, Germany.
Intensive Care Med. 1998 Jul;24(7):663-72. doi: 10.1007/s001340050642.
To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis.
Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial.
Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden.
42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo.
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.
All patients were evaluated for safety and for 30-day all-cause mortality.
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.
评估抗凝血酶III（AT III）降低严重脓毒症患者死亡率的安全性和潜在疗效。
前瞻性、随机、安慰剂对照、双盲、II期、多中心、跨国临床试验。
比利时、丹麦、荷兰、挪威和瑞典的7个学术医学中心重症监护病房（ICU）。
42例严重脓毒症患者，除接受AT III或安慰剂治疗外，还接受标准支持治疗和抗菌治疗。
患者接受静脉注射负荷剂量3000 IU AT III，随后每12小时给予维持剂量1500 IU，共5天，或等量安慰剂。
对所有患者进行安全性评估和30天全因死亡率评估。
AT III的给药安全且耐受性良好。给药后30天全因死亡率降低了39%（无统计学意义）。死亡率的降低伴随着在ICU停留时间的显著缩短。接受AT III治疗的患者在疾病总体严重程度和器官衰竭评分（急性生理与慢性健康评估II、多器官衰竭、器官系统衰竭）方面表现更好，在治疗开始后不久就很明显。接受AT III治疗的患者在观察期内原有器官衰竭的缓解情况更好，新器官衰竭的发生率更低。一项纳入本研究以及另外两项使用AT III的双盲、安慰剂对照试验（共122例严重脓毒症患者）的荟萃分析证实了这一积极趋势。荟萃分析结果表明，接受AT III治疗的患者30天全因死亡率降低了22.9%。尽管样本量仍然太小，无法得出确定性结论，但荟萃分析明确指出，有必要进行一项足够大规模的III期试验，以证明AT III在治疗严重脓毒症中是否具有有益作用。
