Remimazolam Matches Propofol In Postoperative ICU Sedation Trial

A paper reports results from a multicenter, randomized, single-blind, actively controlled phase 3 non-inferiority trial comparing remimazolam tosylate with propofol, with sedation success rates of 98.1% and 96.2%, respectively (difference 1.9%, 95% CI −3.3% to 7.8%). Researchers enrolled 211 mechanically ventilated ICU patients between March 12 and September 24, 2024, who required sedation for at least 6 hours; most were postoperative (99.1%). The treated cohort had a mean age of 61.1 years, 63.5% were male, and 99.1% were postoperative. Patients were assigned 1:1, with 106 receiving remimazolam tosylate and 105 receiving propofol, for short-term sedation during postoperative intensive care management.

Investigators defined sedation success as maintaining the target sedation range for at least 70% of drug administration time without rescue sedation; the protocol target range corresponded to a Richmond Agitation-Sedation Scale (RASS) of −2 to 1. The primary endpoint was the proportion of patients meeting this definition, and the protocol specified a non-inferiority margin of -8%. Success rates were reported as 98.1% with remimazolam tosylate and 96.2% with propofol for the prespecified comparison, for a between-group difference of 1.9% (95% CI −3.3% to 7.8%). In their conclusion, the authors characterized remimazolam as having non-inferior efficacy versus propofol, with target-sedation attainment described as closely comparable between groups during drug administration.

The investigators used intravenous remimazolam tosylate with a 0.08 mg/kg loading dose and a maintenance infusion of 0 to 2.0 mg/kg/h. Propofol was given with a 0.3 to 0.5 mg/kg loading dose and a maintenance infusion of 0.3 to 4.0 mg/kg/h. Both regimens allowed infusion adjustments or additional doses to maintain the target sedation range during active drug administration. Maximum treatment duration was 24 hours, and mean treatment duration was 11.5±3.6 hours with remimazolam tosylate and 11.1±3.1 hours with propofol. Mean total administered dose was 187.1±134.4 mg versus 593.7±530.9 mg, and overall treatment exposure was short-term in both study arms.

Researchers observed adverse events among treated patients in 76.4% of those receiving remimazolam tosylate and 73.3% receiving propofol. Events were described as mainly mild to moderate, except for one severe event in the propofol group. The investigators report a mean terminal half-life of 1.97±1.62 hours for remimazolam tosylate. The authors concluded that remimazolam showed non-inferior efficacy and good tolerability compared with propofol for this short-term sedation period in postoperative mechanically ventilated ICU patients. Several authors reported being employees of Jiangsu Hengrui Pharmaceuticals, while the remaining authors reported no competing interests.

Key Takeaways

• The authors concluded that remimazolam tosylate demonstrated non-inferior efficacy versus propofol for short-term sedation in largely postoperative mechanically ventilated ICU patients.
• Target sedation was defined by maintaining a RASS range of -2 to 1 without rescue sedation, and mean treatment exposure was about 11 hours in both groups.
• Adverse events were reported at similar overall rates, were mostly mild to moderate, and a mean terminal half-life was reported for remimazolam tosylate.