Hong Zhang,1,* Saiying Wang,2,* Mengchang Yang,3,* Yanjuan Huang,4 Kai Wang,5 Ke Jiang,6 Foquan Luo,7 Xianwen Hu,8 Yi Hong,9 Furong Huang,10 Shuan Jin,11 Feng Qi,12 Shoushi Wang,13 Xiaoqing Zhang,14 Huiyu Luo,15 Langtao Guo,16 Longzhen Zhang,17 Jiangang Li,18 Yongquan Chen,19 Zhong Qin,20 Chun Chen,21 Jianjun Yang,22 Wanwei Jiang,23 Nini Fu,24 Yunfei Ju,24 Yuanyuan Li,24 Juan Wang,24 Wen Ouyang,2 Yi Feng1 

1Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 4Department of Anesthesiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Anesthesiology, People’s Hospital of Rizhao, Rizhao, People’s Republic of China; 6Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 7Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, People’s Republic of China; 8Department of Anesthesiology, The Second Hospital of Anhui Medical University, Anhui, People’s Republic of China; 9Center for Rehabilitation Medicine, Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 10Center for Rehabilitation Medicine, Department of Anesthesiology, The First People’s Hospital of Changde City, Changde, People’s Republic of China; 11Center for Rehabilitation Medicine, Department of Anesthesiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 12Center for Rehabilitation Medicine, Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 13Department of Anesthesiology, Qingdao Central Hospital, University of Healthy and Rehabilitation Sciences, Qingdao, People’s Republic of China; 14Department of Anesthesiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 15Department of Anesthesiology, Xiangyang No. 1 People’s Hospital, Xiangyang, People’s Republic of China; 16Department of Anesthesiology, Chengdu Women’s and Children’s Central Hospital, Chengdu, People’s Republic of China; 17Department of Anesthesiology, Meihekou Central Hospital, Meihekou, People’s Republic of China; 18Department of Anesthesiology, Qujing No. 1 Hospital, Qujing, People’s Republic of China; 19Department of Anesthesiology, Yijishan Hospital, Wannan Medical College, Wuhu, People’s Republic of China; 20Department of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 21Department of Anesthesiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 22Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 23Department of Anesthesiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 24Clinical Research and Development Center, Qilu Pharmaceutical Co., Ltd, Jinan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Feng, Department of Anesthesiology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86 13601083503, Email fengyi@pkuph.edu.cn; doctor_yifeng@sina.com Wen Ouyang, Department of Anesthesiology, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 13974934441, Email ouyangwen139@126.com

Background: The dopamine D2/D3 antagonist amisulpride has demonstrated its superiority and efficacy in prophylaxis of postoperative nausea and vomiting (PONV). Given the branded intravenous amisulpride (Barhemsys®) has not been approved in China, there is unmet clinical need for amisulpride. Our primary objective was to ascertain the efficacy and safety of the generic intravenous amisulpride (QLG2069) in the prophylaxis of PONV.
Methods: In this phase III, multicenter, randomized, double-blind, placebo-controlled study, 551 adult Chinese patients (with ≥ 2 Apfel risk factors for PONV) undergoing elective laparoscopic gynecological or abdominal surgery were randomly allocated in a 1:1 ratio to receive either generic intravenous amisulpride or placebo. The primary endpoint was the complete response (CR) rate, defined as the proportion of patients demonstrating neither emetic episodes (vomiting/retching) nor requiring rescue antiemetics throughout the 24-hour postoperative window.
Results: Totally, 542 patients (amisulpride group: n=275; placebo group: n=267) were included in the full analysis set. Amisulpride demonstrated significantly higher CR rate compared to placebo (53.82% vs 40.07%; P=0.0011) within 24-h postoperative period. Patients treated with intravenous amisulpride exhibited significantly lower incidence of moderate-to-severe nausea (28.36% vs 37.08%; P=0.0266) and emesis (44.73% vs 57.30%; P=0.0030) compared to the incidence in the placebo group. The proportion of patients without nausea was numerically higher (45.09%) in the amisulpride group compared to that in the placebo group (37.45%), although the difference did not reach statistical significance (P=0.0685). No significant difference in the proportions of patients receiving rescue medication was noticed between the two groups (21.09% vs 28.09%; P=0.0569). The incidence of adverse events were comparable in two groups.
Conclusion: The generic intravenous amisulpride was safe and effective in prophylaxis of PONV in Chinese patients with moderate-to-high risk of PONV to were undergoing laparoscopic gynecological or abdominal surgery.

Keywords: generic intravenous amisulpride, postoperative nausea and vomiting, complete response