Safety and efficacy of ciprofol vs.propofol for sedation in intensive care unit patients with mechanical ventilation:a multi-center,open label,randomized,phase 2 trial

作     者：Yongjun Liu Xiangyou Yu Duming Zhu Jun Zeng Qinhan Lin Bin Zang Chuanxi Chen Ning Liu Xiao Liu Wei Gao Xiangdong Guan Yongjun Liu;Xiangyou Yu;Duming Zhu;Jun Zeng;Qinhan Lin;Bin Zang;Chuanxi Chen;Ning Liu;Xiao Liu;Wei Gao;Xiangdong Guan

作者机构：Department of Critical Care MedicineThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Critical Care MedicineThe First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830011China Department of Critical Care MedicineZhongshan HospitalFudan UniversityShanghai 200032China Department of Critical Care MedicineGuangzhou First People's HospitalGuangzhou 510180China Department of Critical Care MedicineQingyuan People's HospitalThe Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan 511518China Department of Critical Care MedicineShengjing Hospital of China Medical UniversityShenyang 110022China Department of Research and DevelopmentHaisco Pharmaceutical Group Co.LtdShanghai 201203China. 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2022年第135卷第9期

页      面：1043-1051页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 100217[医学-麻醉学] 

主　　题：HSK3486 Ciprofol Propofol Sedation Mechanical ventilation 

摘      要：Background:Ciprofol(HSK3486;Haisco Pharmaceutical Group Co.,Ltd.,Chengdu,China),developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial.The phase 2 trial was designed to investigate the safety,efficacy,and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods:In this multicenter,open label,randomized,propofol positive-controlled,phase 2 trial,39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio.The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min,followed by an initial maintenance infusion rate of 0.30 mg·kg^(-1)·h^(-1),which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg^(-1)·h^(-1),whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min,followed by an initial maintenance infusion rate of 1.50 mg·kg^(-1)·h^(-1),which could be adjusted to 0.30-4.00 mg·kg^(-1)·h^(-1)to achieve-2 to+1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration.Results:Of the 39 enrolled patients,36 completed the trial.The median(min,max)of the average time to sedation compliance values for ciprofol and propofol were 60.0(52.6,60.0)min and 60.0(55.2,60.0)min,with median difference of 0.00(95%confidence interval:0.00,0.00).In total,29(74.4%)patients comprising 18(69.2%)in the ciprofol and 11(84.6%)in the propofol group experienced 86 treatment emergent adverse events(TEAEs),the majority being of severity grade 1 or 2.Drug-and sedation-related TEAEs were hypotension(7.7%vs.23.1%,P=0.310)and sinus bradycardia(3.8%vs.7.7%,P=1.000)in the ciprofol and propofol groups,respectively.The plasma concentration-time curves for ciprofol and propofol were similar.Conclusions:ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration:ClinicalTrials.gov,NCT04147416.