HSK3486 用于纤维支气管镜检查患者麻醉/镇静的有效性和安全性：一项多中心、双盲、丙泊酚对照、随机、3 期研究。
Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study.
机构信息
Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, Sichuan, China.
Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha, China.
出版信息
CNS Drugs. 2022 Mar;36(3):301-313. doi: 10.1007/s40263-021-00890-1. Epub 2022 Feb 14.
BACKGROUND
Fiberoptic bronchoscopy is a complex procedure with the need for sufficient patient anesthesia/sedation while maintaining safety. This trial aimed to evaluate the efficacy, safety, and pharmacokinetics of HSK3486 during fiberoptic bronchoscopy.
METHODS
This multicenter, double-blind, randomized, non-inferiority, parallel-group phase 3 trial was conducted in patients who underwent fiberoptic bronchoscopy. Patients randomly received HSK3486 0.4 mg/kg (N = 134) or propofol 2.0 mg/kg (N = 133). The primary efficacy endpoint was the successful rate of fiberoptic bronchoscopy, and secondary efficacy endpoints included successful induction of anesthesia/sedation, duration, time to being fully alert, and time to patient discharge. Safety assessments and drug concentrations were also measured.
RESULTS
A total of 267 patients completed fiberoptic bronchoscopy, with a success rate of 100% and a 95% confidence interval of - 2.8 to 2.8% for the difference between the groups, which met the predesigned criteria of > - 8%, confirming the non-inferiority of anesthesia/sedation produced by HSK3486 compared to propofol. Among the secondary efficacy endpoints, only time to full alertness (median 8.50 vs. 6.00 min, P = 0.012) and time to discharge (median 13.00 vs. 9.87 min, P = 0.002) were slightly longer in the HSK3486 group. The incidence of adverse events was significant lower in the HSK3486 group (52.6 vs. 76.5%, P < 0.001) mainly because of less pain on injection (4.4 vs. 39.4%, P < 0.001) compared to the propofol group. HSK3486 had a similar terminal elimination half-life as propofol.
CONCLUSIONS
HSK3486 exhibited non-inferiority anesthesia/sedation compared to propofol in patients undergoing fiberoptic bronchoscopy, and had a good safety profile with a lower incidence of pain on injection.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04111159, registered on 1 October 2019.
背景
纤维支气管镜检查是一项复杂的操作，需要充分的患者麻醉/镇静，同时保持安全性。本试验旨在评估 HSK3486 在纤维支气管镜检查中的疗效、安全性和药代动力学。
方法
这是一项多中心、双盲、随机、非劣效性、平行组的 3 期临床试验，纳入了接受纤维支气管镜检查的患者。患者随机接受 HSK3486 0.4mg/kg（N=134）或丙泊酚 2.0mg/kg（N=133）。主要疗效终点为纤维支气管镜检查的成功率，次要疗效终点包括麻醉/镇静的诱导成功率、持续时间、完全清醒时间和患者出院时间。还进行了安全性评估和药物浓度测量。
结果
共有 267 例患者完成了纤维支气管镜检查，两组间成功率差异的 95%置信区间为-2.8%至 2.8%，在预设的> -8%标准范围内，证实了 HSK3486 与丙泊酚相比在麻醉/镇静方面的非劣效性。在次要疗效终点中，只有完全清醒时间（中位数 8.50 与 6.00 分钟，P=0.012）和出院时间（中位数 13.00 与 9.87 分钟，P=0.002）在 HSK3486 组稍长。HSK3486 组的不良事件发生率显著低于丙泊酚组（52.6%与 76.5%，P<0.001），主要是因为注射疼痛的发生率较低（4.4%与 39.4%，P<0.001）。HSK3486 的终末消除半衰期与丙泊酚相似。
结论
HSK3486 在接受纤维支气管镜检查的患者中表现出与丙泊酚相当的麻醉/镇静效果，且注射疼痛发生率较低，安全性良好。
试验注册
Clinicaltrials.gov，NCT04111159，于 2019 年 10 月 1 日注册。
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