Remimazolam tosilate in patients undergoing upper gastrointestinal endoscopy: a multicenter, randomized, dose-exploration, positive-controlled, parallel-group, phase II trial

IntroductionTo assess both the safety and efficacy of different doses of remimazolam tosilate (HR7056) in maintaining suitable sedation during upper gastrointestinal endoscopy and the reversibility of HR7056’s sedative effects with flumazenil.Material and methodsA total of 156 patients were enrolled and randomly received propofol (group A), 1 of 3 induction doses of HR7056 (8.0 mg (group B), 7.0 mg (group C), 5.0 mg (group D)), or 5.0 mg of HR7056 plus flumazenil (group E). The primary efficacy endpoint was the successful sedation rate. Adverse events (AEs) were recorded to evaluate safety.ResultsBaseline characteristics of patients were well balanced between five treatment groups. For the dose-exploration part, there were no significant difference in successful sedation rate, rates of hypotension and respiratory depression between the four treatment groups. The sedative recovery time in group A was significantly higher than that in group B. The rate of hypoxemia and pain on injection in group A were both significantly higher than those in groups B, C and D. For the flumazenil reversal part, there was no significant difference in the sedative recovery time between group D and group E. The rates of AEs in groups A, B, C, D, E were 40.00%, 29.03%, 16.13%, 6.45%, 6.67%, respectively. There were no serious AEs.ConclusionsHR7056 was comparable to propofol in safety and efficacy in maintaining sedation during upper gastrointestinal endoscopy. HR7056 5.0/2.5 mg-dose (initial dose 5.0 mg, combined with supplemental doses of 2.5 mg) was capable of inducing rapid sedation without the need for flumazenil reversal.