Phase III Trial of Alvimopan, a novel, peripherally acting, Mu Opioid antagonist, for postoperative ileus after major abdominal surgery
Phase III Trial of Alvimopan, a novel, peripherally acting, Mu Opioid antagonist, for postoperative ileus after major abdominal surgery
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DOI：
10.1007/s10350-005-0035-7
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发表时间：
2005-06-01
影响因子：
3.9
通讯作者：
Wallin, BA
中科院分区：
文献类型：
--
作者：
Delaney, CP;Weese, JL;Wallin, BA
目得：术后肠梗阻带来了重大的临床挑战，可能会延长住院时间，导致再次住院，并增加发病率。目前尚无获批的术后肠梗阻治疗方法。Alvimopan是一种新型外周作用μ阿片受体拮抗剂，目前正在开发用于术后肠梗阻的治疗。方法：接受部分结肠切除术或单纯或根治性子宫切除术的患者随机接受alvimopan 6 mg（n = 152）、alvimopan 12 mg（n = 146）或安慰剂（n = 153），术前2小时口服，此后每天两次，直至出院或最多7天。主要疗效终点，胃肠功能恢复时间，是一个复合指标的排气或粪便和耐受固体食物。次要终点包括到出院书面通知的时间。在整个研究期间监测不良事件。研究结果：与安慰剂相比，接受alvimopan 6 mg治疗的患者的胃肠道恢复平均时间显著缩短（风险比= 1.45; P = 0.003），接受alvimopan 12 mg治疗的患者减少幅度较小（风险比= 1.28; P = 0.059）。在接受Alvimopan 6 mg治疗的患者中，至出院书面医嘱的平均时间显著加快（风险比= 1.50; P < 0.001）。所有治疗组中最常见的治疗后出现的不良事件是恶心，呕吐和低血压;在alvimopan 12 mg组中，恶心和呕吐的发生率降低了53%。结论：在接受腹部大手术的患者中，与安慰剂相比，alvimopan可加速胃肠道恢复和出院时间，并且耐受性良好。
PURPOSE: Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus. METHODS: Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study. RESULTS: Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group. CONCLUSIONS: In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.