Study Protocol of a Multicenter, Randomized, Single-Blind Trial: Efficacy and Safety of Remimazolam Tosylate for Sedation in ICU Patients

Introduction: Pharmacodynamic and pharmacokinetic studies in animal experiments and a phase 1 study suggested remimazolam tosylate as an effective and safe sedation/anesthetic agent. However, the effects and safety dose of remimazolam for light sedation in intensive care unit (ICU) patients are not clear and should be confirmed in a phase 2 study.

Methods: Sixty ICU patients requiring sedation treatment and undergoing mechanical ventilation will be enrolled and randomly assigned to a high dose group (HD group, 30 cases) and a low dose group (LD group, 30 cases) in a 1:1 ratio. Patients in both groups will be sedated using remimazolam tosylate in a primary dose of 0.08 mg/kg and a range of 0-2.0 mg/kg/h after randomization. Dose adjustment will be made at the range of every 0.1 mg/kg/h in the LD group and 0.2 mg/kg/h in the HD group to maintain the target Richmond Agitation and Sedation Score (RASS) at - 2 to + 1. The primary outcome will be the proportion of subjects that meet the following conditions: the time within the range of RASS (- 2 to + 1) accounts for 70% of the study drug administration time; without other rescue treatments. Secondary outcomes including the percentage time to reach the sedation goal; the proportion of subjects receiving rescue sedation and/or analgesic, and the mean dose of rescue drug throughout the study period; duration of mechanical ventilation; recovery time to full consciousness and nursing scores. Evaluations of safety including adverse events (AEs), serious AEs, physical examination, laboratory examination, etc. OUTCOME: The results of this study will provide crucial information for the use of remimazolam tosylate for ICU sedation.

Trial registration: ClinicalTrials.gov identifier, NCT05152303.