Zhong Yinbo, Xu Younian, Lei Qian, Yang Mengchang, Wang Saiying, Hu Xiaoling, Xie Haihui, Li Yalan, Qin Zhong, Gu Zhengfeng, Zhang Jiaqiang, Wang Yuexin, Wu Jinglei, Wang Haiying, Ming Yue, Xia Zhongyuan, Zhai Haoyu, Jiang Ke, Zhang Peng, Wang Zhiping, Wang Liangrong, Li Lin, Cheng Zhigang, Jiang Huayong, Wang Guonian, Chen Jingli, Zhao Zhibin, Chen Xiangdong, Yan Min
Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nat Commun. 2025 May 24;16(1):4830. doi: 10.1038/s41467-025-60013-y.
HSK21542, a peripherally restricted kappa opioid receptor agonist, was evaluated for efficacy and safety in patients with postoperative pain following abdominal surgery. This was assessed in two phase 3, multicentre, randomized, double-blind, controlled trials (HSK21542-301 [ClinicalTrials.gov identifier, NCT04738357] and HSK21542-303 [ClinicalTrials.gov identifier, NCT05390905]) in China. HSK21542-301 was a dual-arm study comparing HSK21542 1.0 μg/kg with placebo, while HSK21542-303 involved three arms comparing HSK21542 1.0 μg/kg with tramadol 50 mg/dose and placebo. All treatments were administered intravenously. The primary endpoint was the time-weighted summed pain intensity differences over 24 h (SPID). Both HSK21542-301 (least squares [LS] mean [± standard error], -39.1 [1.88] vs -27.4 [1.89]; P < 0.001) and HSK21542-303 (-64.0 [2.25] vs -45.9 [2.25]; P < 0.001) demonstrated superiority of HSK21542 over placebo in terms of SPID, while HSK21542-303 showed non-inferiority to tramadol (LS mean difference, -1.1; 95% confidence interval, -7.4 to 5.1; P < 0.001). Furthermore, HSK21542 had a comparable safety profile to placebo, inducing fewer gastrointestinal adverse events compared with tramadol. Grade ≥3 treatment-emergent adverse events occurred in eight (5.9%) and three (2.3%) patients in the HSK21542 arm of HSK21542-301 and HSK21542-303, respectively. In conclusion, HSK21542 showed potent analgesic effect and was well tolerated in patients who underwent abdominal surgery and experienced postoperative pain.
HSK21542是一种外周限制性κ阿片受体激动剂，对其在腹部手术后疼痛患者中的疗效和安全性进行了评估。这是在中国进行的两项3期、多中心、随机、双盲、对照试验（HSK21542-301 [ClinicalTrials.gov标识符，NCT04738357]和HSK21542-303 [ClinicalTrials.gov标识符，NCT05390905]）中进行评估的。HSK21542-301是一项双臂研究，将1.0μg/kg的HSK21542与安慰剂进行比较，而HSK21542-303涉及三个臂，将1.0μg/kg的HSK21542与50mg/剂量的曲马多和安慰剂进行比较。所有治疗均通过静脉给药。主要终点是24小时内时间加权疼痛强度差异总和（SPID）。HSK21542-301（最小二乘法[LS]均值[±标准误]，-39.1 [1.88]对-27.4 [1.89]；P < 0.001）和HSK21542-303（-64.0 [2.25]对-45.9 [2.25]；P < 0.001）在SPID方面均显示HSK21542优于安慰剂，而HSK21542-303显示与曲马多非劣效（LS均值差异，-1.1；95%置信区间，-7.4至5.1；P < 0.001）。此外，HSK21542的安全性与安慰剂相当，与曲马多相比，胃肠道不良事件更少。在HSK21542-301和HSK21542-303的HSK21542治疗组中，分别有8名（5.9%）和3名（2.3%）患者发生≥3级治疗中出现的不良事件。总之，HSK21542在接受腹部手术并经历术后疼痛的患者中显示出强效镇痛作用且耐受性良好。
