Efficacy and safety of remimazolam tosylate for sedation in ICU patients: A multicenter, randomized, phase 2 study

Effective sedation in intensive care unit (ICU) patients is critical for minimizing agitation, ensuring safety, and facilitating mechanical ventilation. Remimazolam tosylate, a novel benzodiazepine with rapid onset and short duration, metabolized by tissue esterases, represents a promising agent for ICU sedation. This study aimed to evaluate the efficacy and safety of remimazolam tosylate in short-term sedation for ICU patients.

This was a multicenter, randomized, dose-finding, phase 2 study. From October 12, 2022 through April 19, 2023, ICU patients requiring mechanical ventilation and sedation for ≥6 h were randomized (1:1) into two groups: low adjustment rate (LAR) group received intravenous remimazolam tosylate with a maintenance rate adjustment of 0.1 mg/kg/h, and high adjustment rate (HAR) group with 0.2 mg/(kg·h). Both groups were initiated at an infusion rate of 0.2 mg/(kg·h) with the same loading dose (0.08 mg/kg) and maintenance range (0-2.0 mg/(kg·h)). The primary outcome was sedation success rate, defined as the percentage of time maintaining targeted sedation for ≥70% of the drug administration period without rescue sedation.

A total of 59 patients completed the study (LAR, n=30; HAR, n=29). Within the limited sample, all patients achieved sedation success. The median percentage of time within the target sedation maintenance relative to remimazolam administration duration was 97.9% (IQR: 93.8%-99.7%) for LAR group and 98.1% (IQR: 93.6%-99.8%) for HAR group (P=0.7617). No patients required rescue sedation with propofol, and only one patient (3.3%) in LAR group required rescue analgesia with sufentanil. Most treatment-emergent adverse events (TEAEs) were mild or moderate, with hypotension (18.6%), hypertension (18.6%), and anemia (16.9%) being the most common. One serious TEAE (3.4%, disease progression) and one death were reported in HAR group, both were assessed as unrelated to remimazolam tosylate.

Remimazolam tosylate demonstrated high efficacy with manageable safety profile for short-term sedation in mechanically ventilated ICU patients at both 0.1 mg/(kg·h) and 0.2 mg/(kg·h) adjustment rates.Trial registration: ClinicalTrials.gov, NCT05152303.