A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial)
A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial)
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DOI：
10.1016/j.jtcvs.2011.06.001
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发表时间：
2012-05-01
影响因子：
6
通讯作者：
Levy, Jerrold H.
中科院分区：
文献类型：
--
作者：
Bokesch, Paula M.;Szabo, Gabor;Levy, Jerrold H.
目的：Ecallantide是一种重组肽，与抑肽蛋白同属一类，可抑制血浆钾激肽，钾激肽是接触凝血和炎症级联反应的主要成分。因此，ecallantide有望减少与需要体外循环的心脏手术相关的失血。方法：这项前瞻性、多国、随机、双盲试验纳入了接受心脏手术的患者，这些患者使用体外循环进行与出血高风险相关的手术。患者被随机分配到ecallantide （n = 109）或氨甲环酸（高剂量，n = 24；低剂量，n = 85）组。通过术后12小时内给药的红细胞填充量来评估疗效。结果：在独立数据安全和监测委员会观察到ecallantide组的30天死亡率（12%）显著高于氨甲环酸组（4%,P = 0.041）后，研究提前终止。接受ecallantide治疗的患者在手术12小时内比接受氨甲环酸治疗的患者获得更多的红细胞：中位数= 900 mL(95%可信区间，600-1070)vs 300 mL(95%可信区间，0-523)（P < .001）。在24小时和出院时也有类似的差异。氨甲环酸高剂量组患者的红细胞填充量为0 mL(95%可信区间，280-600)，低于低剂量组（400 mL， 95%可信区间，0-400）（P = 0.008）。高剂量氨甲环酸组无死亡发生。结论：Ecallantide减少围手术期出血量的效果不如氨甲环酸。高剂量氨甲环酸比低剂量氨甲环酸在减少失血方面更有效。（中华胸心外科杂志；2012;43:1022-9）
Objective: Ecallantide is a recombinant peptide in the same class as aprotinin that inhibits plasma kallikrein, a major component of the contact coagulation and inflammatory cascades. Therefore, ecallantide was expected to reduce blood loss associated with cardiac surgery requiring cardiopulmonary bypass.Methods: This prospective multinational, randomized, double-blind trial enrolled patients undergoing cardiac surgery using cardiopulmonary bypass for procedures associated with a high risk of bleeding. Patients were randomly assigned to ecallantide (n = 109) or tranexamic acid (high dose, n = 24; low dose, n = 85). Efficacy was assessed from the volume of packed red blood cells administered within the first 12 hours after surgery.Results: The study was terminated early after the independent data safety and monitoring board observed a statistically significantly higher 30-day mortality in the ecallantide group (12%) than in the tranexamic acid groups (4%, P = .041). Patients receiving ecallantide received more packed red blood cells within 12 hours of surgery than tranexamic acid-treated patients: median = 900 mL (95% confidence interval, 600-1070) versus 300 mL (95% confidence interval, 0-523) (P < .001). Similar differences were seen at 24 hours and at discharge. Patients treated with the higher tranexamic acid dose received less packed red blood cells, 0 mL (95% confidence interval, 280-600), than the group treated with the lower dose, 400 mL (95% confidence interval, 0-400) (P = .008). No deaths occurred in the higher dose tranexamic acid group.Conclusions: Ecallantide was less effective at reducing perioperative blood loss than tranexamic acid. High-dose tranexamic acid was more effective than the low dose in reducing blood loss. (J Thorac Cardiovasc Surg 2012; 143: 1022-9)