Rolapitant for the Prevention of Postoperative Nausea and Vomiting: A Prospective, Double-Blinded, Placebo-Controlled Randomized Trial
Rolapitant for the Prevention of Postoperative Nausea and Vomiting: A Prospective, Double-Blinded, Placebo-Controlled Randomized Trial
复制标题
DOI：
10.1213/ane.0b013e31820886c3
复制
发表时间：
2011-04-01
影响因子：
5.7
通讯作者：
Cantillon, Marc
中科院分区：
文献类型：
--
作者：
Gan, Tong J.;Gu, Jiezhun;Cantillon, Marc
背景：术后恶心呕吐（PONV）是手术后常见的并发症。神经激肽-1（NK 1）受体拮抗剂已被证明可安全有效地预防和治疗人类PONV。罗拉匹坦是一种有效的选择性NK 1受体拮抗剂，吸收迅速，半衰期长（长达180小时），药物间相互作用的可能性较低。我们评估了罗拉匹坦在高危受试者中预防PONV的剂量反应，并探讨了罗拉匹坦在手术后5天内预防迟发性PONV的效果。方法：一项随机、多中心、双盲、剂量范围罗拉匹坦研究，包括安慰剂组和活性对照组。619名接受开腹手术的成年女性按等比例随机分配到6个研究组中的1个：口服罗拉匹坦5 mg、20 mg、70 mg或200 mg剂量;静脉注射昂丹司琼4 mg;或安慰剂，按PONV或运动病史分层。主要研究终点是无呕吐发作，无论使用急救药物，在拔管后24小时。结果：分配到罗拉匹坦20 mg，70 mg，200 mg组有较高的发生率，与安慰剂相比，在手术后24小时无呕吐。罗拉匹坦剂量和主要结果之间存在线性关系。与安慰剂组相比，罗拉匹坦70 mg和200 mg组呕吐发作的概率显著降低（P
BACKGROUND: Postoperative nausea and vomiting (PONV) are common complications after surgery. Neurokinin-1 (NK1) receptor antagonists have been shown to be safe and effective for the prevention and treatment of PONV in humans. Rolapitant is a potent, selective NK1 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 women undergoing 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 mg; 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-mg 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