Rolapitant预防术后恶心呕吐：一项前瞻性、双盲、安慰剂对照的随机试验  

作　　者：Tong J. Gan Jiezhun Gu Neil Singla Frances Chung Michael H. Pearman Sergio D. Bergese Ashraf S. Habib Keith A. Candiotti Yi Mo Susan Huyck Mary R. Creed Marc Cantillon Rolapitant Investigation group 黄礼兵(译) 崔苏扬(校) 

机构地区：[1]Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina [2]Department of Clinical Trials Statistics, Duke Clinical Research Institute, Durham, North Carolina [3]Lotus Clinical Research, Inc., Arcadia, California [4]Department of Anesthesia, University Health Network, University of Toronto, Toronto, Ontario, Canada [5]Department of Anesthesia, Jane Phillips Medical Center, Bartlesville, Oldahoma [6]Department of Anesthesiology and Neurological Surgery, Ohio State University, Columbus, Ohio [7]Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina [8]University of Miami, Miami, Florida tt Schering-Plough Research Institute, Kenilworth, New Jersey [9]Duke Clinical Research Institute, Durham, North Carolina [10]See the Appendix for a full listing of Rolapitant Investigation group participating investigators [11]不详

出　　处：《麻醉与镇痛》2012年第4期23-30,共8页Anesthesia & Analgesia

摘　　要：背景术后恶心呕吐（postoperativenauseaandvomiting，PONV）是一种常见的术后并发症。研究证实神经激肽．1（neurokinin一1，NK，）受体拮抗剂可以安全有效地用于预防和治疗人类PONV。Rolapitant（罗纳吡坦）为一种吸收迅速、半衰期相当长（达180小时）的强效选择性NK、受体拮抗剂，潜在的药物相互作用低。我们对Rolapitant用于预防PONV高危人群的量效关系以及术后5天的预防迟发性IK）NV的效果进行了研究。方法这项关于Rolapitant的随机、多中心、双盲、有效剂量范围的研究设有安慰剂组和阳性对照组。纳入619例行开腹手术的成年妇女，基于PONV或晕动病史进行分层，分为6个研究组：Rolapitant口服剂量5mg组、20mg组、70nag组或200mg组；静注昂丹司琼4mg组或安慰剂组。主要研究终点：不考虑补救用药，拔管后24小时的无呕吐发生率。结果Rolapitant20mg、70mg或200mg组患者的术后24小时无呕吐发生率高于安慰剂组。Rolapitant剂量与主要转归呈线性相关。与安慰剂组相比，Rolapitant70mg和200mg组的呕吐次数明显更低（P≤0．001，对数秩和检验）。尽管术后24小时无呕吐次数在Rolapitant组和昂丹司琼对照组没有明显差异，但Rolapitant200mg组和70mg组的术后72小时和120小时无呕吐发生率更高（不考虑补救用药）。结论Rolapitant降低术后呕吐的疗效优于安慰剂，呈剂量依赖性地降低呕吐发生率。而且Rolapitant与安慰剂在不良反应方面没有差异。BACKGROUND： Postoperative nausea and vomiting （PONV） are common complications after surgery. Neurokinin-i （NI（1 ） receptor antagonists have been shown to be safe and effective for the prevention and treatment of PONV in humans. Rolapitant is a potent, selective NIG receptor antagonist that is rapidly absorbed, has a remarkably long half-life （up to180 hours）, and appears to have a low potential for drug - drug interactions. We evaluated the dose response for rolapitant for the prevention of PONV in subjects at high risk for this condition, and rolapitant＇s effects on preventing delayed PONV were explored up to 5 days after surgery. METHODS： A randomized, multicenter, double-blind; dose- ranging study of rolapitant was conducted with placebo and active control groups. Six hundred nineteen adult womenundergoing open abdominal surgery were randomly assigned in equal ratios to 1 of 6 study arms： oral rolapitant in 5-mg, 20- mg, 70-mg, or 200-mg doses; IV ondansetron 4 rag; or placebo, stratified by history of PONV or motion sickness. The primary study endpoint was absence of emetic episodes, regardless of use of rescue medication, at 24 hours after extubation. RESULTS： Groups assigned to rolapitant 20-mg, 70-mg, and 200-rag had a higher incidence of no emesis in comparison with placebo at 24 hours after surgery. A linear relationship between rolapitant dose and primary outcome was seen. The probability of an emetic episode was significantly lower in the rolapitant 70-mg and 200-mg groups in comparison with placebo （P 〈~ 0.001 based on the log-rank test）. No significant differences were noted between rolapitant and the active control （ondansetron） at 24 hours after surgery, but there was a higher inddence of no emesis （regardless of rescue medication use） in the rolapitant 200- and 70-mg groups at 72 and 120 hours, respectively. CONCLUSIONS： Rolapitant is superior to placebo in reducing emetic episodes after surgery and reduces the incidence of vomiting in a dose-dependent manne

关 键 词：术后恶心呕吐 安慰剂对照 随机试验 预防 双盲 受体拮抗剂 阳性对照组 PONV 

分 类 号：R442.1[医药卫生—诊断学]