Once Daily YM150, an Oral Direct Factor Xa Inhibitor, for Prevention of Venous Thromboembolism in Patients Undergoing Elective Primary Hip Replacement.
Once Daily YM150, an Oral Direct Factor Xa Inhibitor, for Prevention of Venous Thromboembolism in Patients Undergoing Elective Primary Hip Replacement.
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每日一次 YM150，一种口服直接 Xa 因子抑制剂，用于预防接受选择性初次髋关节置换术的患者的静脉血栓栓塞。
DOI：
10.1182/blood.v110.11.309.309
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发表时间：
2007
期刊：
影响因子：
20.3
通讯作者：
L. Meems
中科院分区：
文献类型：
--
作者：
B. Eriksson;A. Turpie;M. Lassen;M. Prins;G. Agnelli;P. Kälebo;G. Wetherill;L. Meems
YM 150是一种口服活性的直接FXa抑制剂，正在临床开发中。先前在剂量递增研究中获得了YM 150的概念证明，证明了在接受全髋关节置换术的患者中预防VTE的统计学显著剂量相关趋势（ONYX; J Thromb Haemost 2007;5：1660-5）。本研究是一项在接受择期初次髋关节置换术的患者中进行的双盲、平行、多中心剂量探索研究，以开放标签依诺肝素作为对照。患者随机接受5、10、30、60或120 mg YM 150每日一次口服或40 mg依诺肝素每日一次皮下注射治疗。患者在医院治疗约1-2周，然后在家治疗另外4周，总共治疗33-38天（根据Am.美国胸科医师学会（Geoffrey等人，Chest 2004：126;338-400））。YM 150的给药在手术后6-10小时开始，而依诺肝素的治疗在手术前12 ± 2小时开始。治疗7-10天后进行强制性双侧静脉造影。在家庭治疗期间的第2周和第4周以及研究治疗结束后的第2周、第4周和第8周进行随访访视。估计样本量为960例随机化患者，以便每个治疗组产生110例具有可评价静脉造影的患者。主要疗效终点定义为深静脉血栓形成和/或症状性VTE和/或死亡，主要安全性终点定义为研究治疗前7-10天内大出血的发生率。次要疗效终点为近端和远端DVT（前7-10天内）以及家庭治疗和随访期间的症状性VTE。次要安全性终点为3个研究阶段内的重大、临床相关非重大（CRNM）和轻微出血的发生率。独立裁定委员会审查了所有静脉造影、出血报告、症状性VTE和不知道治疗分配的死亡。独立的DSMB监测数据，以确保患者的安全性。从17个欧洲国家的81个研究中心随机分配了1017例患者。初步数据显示，在727例可评价的静脉造影中，149例检测到DVT，1例患者有症状性VTE，1例患者在住院治疗期间死亡（心肌梗死）。这导致可评价研究人群的总主要疗效结局率为20.7%（151/729），相应的大出血发生率为0.6%（6/1017）。将按治疗组列出结果的细分。
YM150 is an orally active direct FXa inhibitor in clinical development. Proof of concept of YM150 was previously obtained in a dose escalation study, demonstrating a statistically significant dose-related trend in VTE prevention in patients undergoing total hip replacement (ONYX; J Thromb Haemost 2007;5:1660–5). The present study with YM150 is a double blind, parallel, multi-center dose finding study in patients undergoing elective primary hip replacement surgery, with open label enoxaparin as control. Patients were randomly treated with 5, 10, 30, 60 or 120 mg YM150 once daily orally or 40 mg enoxaparin once daily subcutaneously. Patients were treated in hospital for approximately 1–2 weeks followed by home treatment for another 4 weeks, for in total 33–38 treatment days (prolonged treatment for hip replacements according to guidelines of Am. College of Chest Physicians (Geerts et al. Chest 2004:126;338–400)). The administration of YM150 started 6–10 h after surgery, while treatment with enoxaparin started 12 ± 2 h before surgery. Mandatory bilateral venography was performed after 7–10 days of treatment. Follow up visits were performed at 2 and 4 weeks during home treatment, and 2, 4, and 8 weeks after end of study treatment. The sample size was estimated to be 960 randomized patients in order to yield 110 patients per treatment group with an evaluable venogram. The primary efficacy endpoint was defined as deep vein thrombosis, and/or symptomatic VTE and/or death, and primary safety endpoint as the incidence of major bleeding during the first 7–10 days of study treatment. Secondary efficacy endpoints were proximal and distal DVT (during the first 7–10 days) and symptomatic VTE during home treatment, and follow up. Secondary safety endpoints were the incidences of major, clinically relevant non-major (CRNM) and minor bleeding during the three study periods. Independent Adjudication Committees reviewed all venograms, bleeding reports, symptomatic VTEs, and deaths unaware of treatment allocation. An independent DSMB monitored the data to ensure the safety of the patients. 1017 patients were randomized from 81 sites in 17 European countries. Preliminary data showed that DVT was detected in 149 out of 727 evaluable venograms, one patient had symptomatic VTE, and one patient died (myocardial infarction) during the hospital treatment period. This results in a total primary efficacy outcome rate of 20.7% (151/729) in the evaluable study population, with a corresponding rate of major bleeding of 0.6% (6/1017). The breakdown of the results according to treatment group will be presented.