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Background: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium., Methods: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg -1 ) or sugammadex (2 mg kg -1 ) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected., Results: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047)., Conclusions: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile., Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg−1) or sugammadex (2 mg kg−1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg−1 (n = 16) and 6 mg kg−1 (n = 20) adamgammadex- and 2 mg kg−1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg −1 adamgammadex-induced median recovery time was longer than that of 2 mg kg−1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg −1 adamgammadex group and 2 mg kg−1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg−1 and sugammadex at 2 mg kg−1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex. [ABSTRACT FROM AUTHOR]