The efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy: a multicentered, randomized, positive-controlled, phase III clinical trial.

Abstract

This study aimed to evaluate the efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy. In this multicentered, blinded, randomized, active-controlled, non-inferior phase III trial, 384 eligible patients who were about to undergo colonoscopy were randomized as a ratio of 1:1 into remimazolam and propofol group. Procedure success was assessed and defined as the completion of colonoscopy without administration of rescue sedative agent or more than 5 top-ups of trial drug in any 15 minute-period after initial administration of trial drug. Sedation quality was evaluated by Modified Observer's Assessment of Alertness/Sedation score. Treatment-emergent adverse events were recorded. Procedure success rate was 96.91% (188/194) in remimazolam group and 100% (190/190) in propofol group, and the difference in rate was -3.09% with 95% confidence interval (CI) of -5.53%~-0.66%. Since the lower limit of 95% CI was greater than the non-inferiority margin of -8.00%, the efficacy of remimazolam tosylate was non-inferior to propofol. Besides, induction time of sedation was increased (<i>P</i><0.001), while hypotension and respiratory depression was decreased in remimazolam group compared to propofol group; however, time to fully alert (<i>P</i>>0.05) or time to discharge (<i>P</i>>0.05) were unchanged. For safety assessment, total treatment-emergent adverse events were decreased in remimazolam group compared to propofol group (<i>P</i><0.001); specifically, administration site pain (<i>P</i><0.001), increased bilirubin (<i>P</i>=0.019), decreased respiratory rate (<i>P</i><0.001) and decreased SpO₂ (<i>P</i><0.001) were less frequent in remimazolam group compared with propofol group. In conclusion, remimazolam tosylate is non-inferior in sedation efficacy while safer than propofol in patients undergoing colonoscopy.