Duke Clinical Research Institute, Durham, NC, USA.
Circulation. 2010 Apr 20;121(15):1713-21. doi: 10.1161/CIRCULATIONAHA.109.913277. Epub 2010 Apr 5.
Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low-molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low-molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention.
Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention-related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable.
This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400.
因子 Xa 和因子 IIa（凝血酶）在经皮冠状动脉介入治疗后的血栓并发症中发挥作用。M118 是一种新型低分子量肝素，经过合理设计，兼具未分级肝素（UFH）和低分子量肝素的理想特性：对因子 Xa 和 IIa 具有强大的活性、静脉和皮下给药后具有可预测的药代动力学、可通过即时凝血检测进行监测、并可用硫酸鱼精蛋白逆转。我们进行了一项 2 期随机试验，以评估 M118 在择期经皮冠状动脉介入治疗中的安全性和可行性。
总体而言，在美国和加拿大的 43 个中心，503 名接受择期经皮冠状动脉介入治疗的患者以开放标签的方式随机分为 4 组：UFH 70 U/kg、M118 50IU/kg IV、M118 75IU/kg IV 或 M118 100IU/kg IV。主要结局是死亡、心肌梗死、再次血运重建、卒中和血小板减少症、导管血栓形成、挽救性使用糖蛋白 IIb/IIIa 抑制剂或 30 天内任何出血的复合终点。随机分配至 UFH 的患者中主要终点的发生率为 31.1%，随机分配至 M118 50、75 和 100IU/kg 的患者中主要终点的发生率分别为 22.7%、28.3%和 30.1%。比较 M118 各组与 UFH 之间主要终点发生率的主要分析表明，M118 在预防经皮冠状动脉介入治疗相关并发症方面不劣于 UFH（M118 联合治疗组的发生率为 28.4%，而 UFH 组为 31.1%）。M118 和 UFH 的不良事件谱相似。
这项 2 期随机试验表明，M118 耐受性良好，可作为择期经皮冠状动脉介入治疗患者的抗凝剂使用，并为该药物在缺血性心脏病中的进一步研究奠定了基础。
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