Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular block: a multicentre, randomised, double-blind, positive-controlled phase III trial PMID: 40461346

ADC Targets in Oncology

2026-04-10

Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular block: a multicentre, randomised, double-blind, positive-controlled phase III trial

Br J Anaesth. 2025 Aug;135(2):331-339. doi: 10.1016/j.bja.2025.04.031.

Yanhua Zhao ¹ , Yuqing Ren ¹ , Wenqin Xie ² , Yulan Wang ³ , Yishan Lei ³ , Yingxia Zhu ⁴ , Xiaoqing Zhang ⁴ , Xiaozhi Wu ⁵ , Xiaoming Guo ⁵ , Yingying Jiang ⁶ , Saiying Wang ⁷ , Qian Lei ⁸ , Jiyue You ⁸ , Yonghao Yu ⁹ , Yinhui Zhou ¹⁰ , Wenjuan Zhou ¹⁰ , Guohai Xu ¹¹ , Chang Li ¹¹ , Zhengfeng Gu ¹² , Foquan Luo ¹³ , Hongfa Wang ¹³ , Junping Chen ¹⁴ , Ruichun Wang ¹⁴ , Youmao Qi ¹⁵ , Qing Jie ¹⁵ , Diansan Su ¹⁶ , Xiyao Gu ¹⁷ , Weifeng Yu ¹⁸

Affiliations

1. Department of Anaesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China.
2. Department of Anaesthesiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
3. Department of Anaesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
4. Department of Anaesthesiology, Tongji Hospital of Tongji University, Shanghai, China.
5. Department of Anaesthesiology, The 900 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Fuzhou, China.
6. Department of Anaesthesiology, West China Hospital, Sichuan University, Chengdu, China.
7. Department of Anaesthesiology, Third Xiangya Hospital, Central South University, Changsha, China.
8. Department of Anaesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
9. Department of Anaesthesiology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.
10. Department of Anaesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
11. Department of Anaesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
12. Department of Anaesthesiology, Wuxi People's Hospital, Nanjing Medical University, Wuxi, China.
13. Department of Anaesthesiology, Zhejiang Provincial People's Hospital Hangzhou Medical College, Zhejiang, China.
14. Department of Anaesthesiology, Ningbo No.2 Hospital, Ningbo, China.
15. Hangzhou Adamerck Pharmlabs Inc., Hangzhou, China.
16. Department of Anaesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: [email protected].
17. Department of Anaesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: [email protected].
18. Department of Anaesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anaesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address: [email protected].

Abstract

Background: Adamgammadex, a newly developed modified γ-cyclodextrin derivative, has demonstrated efficacy in reversing deep rocuronium-induced neuromuscular block in early clinical trials.

Methods: This multicentre, randomised, double-blind, positive-controlled, noninferiority phase III clinical trial aimed to investigate the efficacy and safety of adamagammadex compared with sugammadex in reversing deep rocuronium-induced neuromuscular block. In total, 321 patients were randomly assigned to either the adamgammadex 8 mg kg^-1 group or the sugammadex 4 mg kg^-1 group. The primary outcome was the success rate of antagonism, defined as recovery of the train-of-four ratio (TOFR) to 0.9 within 10 min. Standard safety data were collected throughout the trial period.

Results: For the primary efficacy outcome, the success rate for recovery of TOFR to 0.9 was 98.7% in the adamgammadex group and 100% in the sugammadex group, with an observed difference of -1.3% (95% confidence interval [CI] -4.6%, 1.2%). The lower limit of -4.6% was higher than the noninferiority margin of -10%. For the key secondary efficacy outcomes, the median (interquartile range) time from administration of adamgammadex or sugammadex to recovery of TOFR to 0.9 was 2.5 (2.0, 3.2) min and 2.2 (1.7, 2.7) min, respectively. The difference was 0.5 min (95% CI 0.3, 0.7), and the upper limit of 0.7 min was lower than the noninferiority margin of 5 min. We observed no inferiority in secondary efficacy outcomes. There was no significant difference in the safety profile between adamgammadex and sugammadex.

Conclusions: Adamgammadex was noninferior to sugammadex in reversing deep neuromuscular block from rocuronium.

Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR2200056471, registered February 6, 2022; https://www.chictr.org.cn/showproj.html?proj=141077).

Keywords

adamgammadex; neuromuscular blocking agents; phase III study; reversal agents; sugammadex.