Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial
Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial
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DOI：
10.1111/j.1538-7836.2006.02267.x
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发表时间：
2007-01-01
影响因子：
10.4
通讯作者：
Aoki, N.
中科院分区：
文献类型：
--
作者：
Saito, H.;Maruyama, I.;Aoki, N.
背景：可溶性血栓调节蛋白是一种有前途的治疗性天然抗凝剂，与抗凝血酶、组织因子途径抑制剂和活化蛋白 C 相当。 目的：我们进行了一项多中心、双盲、随机、平行组试验，比较重组人可溶性血栓调节蛋白 (ART-123) 与低剂量肝素治疗与血液恶性肿瘤或感染相关的弥散性血管内凝血 (DIC) 的有效性和安全性。方法：DIC患者（n = 234）被分配接受ART-123（0.06 mg kg(-1)，持续30 min，每日一次）或肝素钠（8 U kg(-1) h(-1)，持续24 h）治疗6天，采用双模拟法。主要疗效终点是 DIC 缓解率。次要终点包括出血症状的临床病程和 28 天死亡率。结果：ART-123 组的 DIC 缓解率为 66.1%，而肝素组的缓解率为 49.9% [差异 16.2%； 95% 置信区间 (CI) 3.3-29.1]。 ART-123 组患者的出血症状临床过程也显示出更显着的改善（P = 0.0271）。输注开始后7天内，ART-123组的出血相关不良事件发生率低于肝素组（43.1% vs. 56.5%，P = 0.0487）。结论：与肝素治疗相比，ART-123治疗更能显着改善DIC并减轻DIC患者的出血症状。
Background: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. Objectives: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. Methods: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. Results: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). Conclusions: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.