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.
