奥赛利定治疗全麻患者术后中重度疼痛的有效性和安全性：随机、盲法、阳性对照、多中心临床试验

陈功; 欧阳文; 戴茹萍; 胡啸玲; 郭华静; 蒋海涛; 王志萍; 柴小青; 王纯辉; 夏中元; 罗爱林; 王强; 曾睿峰; 黄燕娟; 赵志斌; 汪赛赢

doi:10.3760/cma.j.cn131073.20231016.00203

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中华麻醉学杂志

• 疼痛诊疗与研究 •

ENGLISH ABSTRACT

奥赛利定治疗全麻患者术后中重度疼痛的有效性和安全性：随机、盲法、阳性对照、多中心临床试验

作者及单位信息

出版日期： 2024 -02 -20 ·

DOI： 10.3760/cma.j.cn131073.20231016.00203

Efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia: a prospective, randomized, double-blinded, multicenter, positive-controlled clinical trial

Authors Info & Affiliations

Chen Gong

Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha 410013, China

Ouyang Wen

Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha 410013, China

Dai Ruping

Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha 410011, China

Hu Xiaoling

Department of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang 421001, China

Guo Huajing

Department of Anesthesiology, The First People′s Hospital of Changde City, Changde 415003, China

Jiang Haitao

Department of Anesthesiology, The Second People′s Hospital of Yueyang City, Yueyang 414000, China

Wang Zhi-ping

Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China

Chai Xiaoqing

Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230000, China

Wang Chunhui

Department of Anesthesiology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230000, China

Xia Zhongyuan

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China

Luo Ailin

Department of Anesthesiology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China

Wang Qiang

Department of Anesthesiology, The First Affiliated Hospital of Xi′an Jiaotong University, Xi′an 710061, China

Zeng Ruifeng

Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China

Huang Yanjuan

Department of Anesthesiology, The Second People′s Hospital of Nanning City, Nanning 530031, China

Zhao Zhibin

Department of Anesthesiology, The First People′s Hospital of Lianyungang City, Lianyungang 222002, China

Wang Saiying

Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha 410013, China

Published： 2024 -02 -20 ·

DOI： 10.3760/cma.j.cn131073.20231016.00203

APP内阅读

摘要

目的评价奥赛利定治疗全麻患者术后中重度疼痛的有效性和安全性。

方法纳入2021年7月6日至11月9日14家医院的全麻腹部手术后中重度疼痛(数字疼痛评分≥4分)患者，采用随机数字表法分为试验组和对照组，分别给予奥赛利定或吗啡负荷剂量＋PCA＋补充剂量治疗24 h。主要有效性指标为给予负荷剂量后24 h内对试验药物应答率。次要有效性指标包括给予负荷剂量后1 h内对试验药物应答率和补救镇痛率。安全性指标包括治疗期间呼吸抑制和其他不良反应的发生率。

结果经随机化分组，本试验中全分析集和安全性分析集均为180例，试验组92例，对照组88例；符合方案集170例，试验组86例，对照组84例。2组给予负荷剂量后24 h内对试验药物应答率、补救镇痛率、呼吸抑制和其他不良反应发生率比较差异无统计学意义( P>0.05)。全分析集分析显示，试验组给予负荷剂量后5～30 min时对试验药物应答率高于对照组( P<0.05)。符合方案集分析显示，试验组给予负荷剂量后5～15 min时对试验药物应答率高于对照组( P<0.05)。

结论奥赛利定用于全麻患者术后中重度疼痛的镇痛效果与吗啡相当，且起效更快。

关键词：镇痛药，阿片类;疼痛，手术后;疼痛管理

ABSTRACT

ObjectiveTo evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.

MethodsThe patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.

ResultsAfter randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05).

ConclusionsWhen used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

KEYWORDS： Analgesics, opioid;Pain, postoperative;Pain management

Corresponding author: Wang Saiying, Email: mocdef.qabq8843031771

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All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

陈功,欧阳文,戴茹萍,等. 奥赛利定治疗全麻患者术后中重度疼痛的有效性和安全性：随机、盲法、阳性对照、多中心临床试验[J]. 中华麻醉学杂志,2024,44(02)：135-139.

DOI:10.3760/cma.j.cn131073.20231016.00203

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*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

编者按

奥赛利定作为G蛋白偏向性μ阿片受体激动剂，其原研是美国Trevena公司，2020年8月7日被FDA批准在美国上市(商品名OLINVYK)。2018年5月恩华药业公司与Trevena公司签署《药品许可及合作协议》，并进行了技术转移和国内药学研究，原料和制剂完全采用Trevena公司技术，实现了中国地产化并通过国家技术审评，2020年6月1日获得临床试验通知书。此论文报告的是我国唯一的、奥赛利定上市前的多中心临床研究，本临床试验按照《药物临床试验质量管理规范》、国际协调会议三方协调指导原则进行，由中南大学湘雅三医院欧阳文教授领衔完成，谨此，在奥赛利定上市后第一时间我刊进行约稿，以飨读者。

术后疼痛是全麻手术患者最常见的并发症之一，如不能得到有效控制，不仅会影响患者的康复质量，还可能导致慢性疼痛的发生 ^{[
1
]} 。因此，术后疼痛的有效治疗极为重要。阿片类药物是缓解术后急性疼痛的经典药物，但传统阿片类药物如吗啡，由于峰效时间较迟，不能很好地满足患者需求。此外，吗啡还存在一定的副作用，如呼吸抑制、恶心呕吐等。因此，开发新型术后疼痛治疗药物仍具有重要意义。奥赛利定(曾用名TRV130)是一种μ阿片受体激动剂，与传统的阿片类药物不同，其主要刺激G蛋白偶联通路，β-arrestin募集作用弱，能够快速产生较强的镇痛效果，并可减少阿片类药物相关不良反应的发生 ^{[
2
]} 。本研究拟评价奥赛利定治疗全麻患者术后中重度疼痛的有效性和安全性，以期为奥赛利定的临床应用提供依据。

摘要
编者按
参考文献

参考文献

[1]

Kehlet H , Jensen TS , Woolf CJ . Persistent postsurgical pain: risk factors and prevention[J]. Lancet， 2006，367(9522)：1618-1625. DOI： 10.1016/S0140-6736(06)68700-X .

返回引文位置Google Scholar

百度学术

万方数据

[2]

Dewire SM , Yamashita DS , Rominger DH ,et al. A G protein-biased ligand at the mu-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine[J]. J Pharmacol Exp Ther， 2013，344(3)：708-717. DOI： 10.1124/jpet.112.201616 .

返回引文位置Google Scholar

百度学术

万方数据

[3]

Viscusi ER , Skobieranda F , Soergel DG ,et al. Apollo-1: a randomized placebo and active-controlled phase Ⅲ study investigating oliceridine (TRV130), a G protein-biased ligand at the μ-opioid receptor, for management of moderate-to-severe acute pain following bunionectomy[J]. J Pain Res， 2019，12：927-943. DOI： 10.2147/JPR.S171013 .

返回引文位置Google Scholar

百度学术

万方数据

[4]

Singla NK , Skobieranda F , Soergel DG ,et al. Apollo-2: a randomized, placebo and active-controlled phase Ⅲ study investigating oliceridine (TRV130), a G protein-biased ligand at the μ-opioid receptor, for management of moderate to severe acute pain following abdominoplasty[J]. Pain Pract， 2019，19(7)：715-731. DOI： 10.1111/papr.12801 .

返回引文位置Google Scholar

百度学术

万方数据

[5]

Viscusi ER , Webster L , Kuss M ,et al. A randomized, phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain[J]. Pain， 2016，157(1)：264-272. DOI： 10.1097/j.pain.0000000000000363 .

返回引文位置Google Scholar

百度学术

万方数据

[6]

Soergel DG , Subach RA , Burnham N ,et al. Biased agonism of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers[J]. Pain， 2014，155(9)：1829-1835. DOI： 10.1016/j.pain.2014.06.011 .

返回引文位置Google Scholar

百度学术

万方数据

[7]

Singla N , Minkowitz HS , Soergel DG ,et al. A randomized, phase Ⅱb study investigating oliceridine (TRV130), a novel μ-receptor G-protein pathway selective (μ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty[J]. J Pain Res， 2017，10：2413-2424. DOI： 10.2147/JPR.S137952 .

返回引文位置Google Scholar

百度学术

万方数据

[8]

Moss L , Hijma H , Demitrack M ,et al. Neurocognitive effect of biased μ-opioid receptor agonist oliceridine, a utility function analysis and comparison with morphine[J]. Anesthesiology， 2023，139(6):746-756. DOI： 10.1097/ALN.0000000000004758 .

返回引文位置Google Scholar

百度学术

万方数据

[9]

Manglik A , Lin H , Aryal DK ,et al. Structure-based discovery of opioid analgesics with reduced side effects[J]. Nature， 2016，537(7619)：185-190. DOI： 10.1038/nature19112 .

返回引文位置Google Scholar

百度学术

万方数据

备注信息

通信作者：汪赛赢，Email： mocdef.qabq8843031771

作者贡献声明

陈功：数据整理、统计学分析、论文撰写；欧阳文：研究指导、试验操作；戴茹萍、胡啸玲、郭华静、蒋海涛、王志萍、柴小青、王纯辉、夏中元、罗爱林、王强、曾睿峰、黄燕娟、赵志斌：试验操作、数据整理；汪赛赢：试验操作、数据整理、论文撰写与修改

临床试验注册：

中国临床试验注册中心，ChiCTR20211381

Trial registration:

Chinese Clinical Trial Registry, ChiCTR20211381

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