Efficacy of remimazolam versus midazolam for outpatient dental sedation: a multicenter, randomized, controlled, non-inferiority trial

Abstract Purpose Intravenous sedation is commonly used in routine dental procedures, however, existing agents are associated with limitations in recovery profiles and postoperative complications. Remimazolam has emerged as a promising alternative to address these clinical challenges. This study aimed to establish the non-inferiority of titrated remimazolam compared to midazolam concerning both efficacy and safety endpoints in dental extraction procedures. Methods This randomized, single-blind, parallel-controlled, non-inferiority study was conducted across 13 centers in China from September 2021 to July 2023. A total of 612 eligible patients scheduled for dental extraction were randomized to receive either remimazolam (group R, initial dose of 0.1 mg/kg with 2 mg top-ups; n = 307) or midazolam (group M, initial dose of 0.05 mg/kg with 1 mg top-ups; n = 305). The primary endpoint was the sedation success rate, with a predefined non-inferiority margin of 6%. Secondary outcomes included recovery time, discharge readiness, adverse events, and 24-h postoperative complications. Results Remimazolam demonstrated non-inferior efficacy, achieving success rates of 99.0% compared to 96.1% for midazolam (adjusted risk difference, 95% confidence interval, 2.81 −1.29 to 6.91; adjusted P = 0.179). Patients in group R recovered faster and were discharged earlier than patients in group M (5 3, 6 vs. 7 4, 10 min, P < 0.001; and 46 38, 53 vs. 52 44, 60 min, P < 0.001). Additionally, patients in group R exhibited a significantly lower incidence of 24-h postoperative adverse reactions (4.6% vs. 12.1%; adjusted P = 0.030). Conclusions Titrated remimazolam demonstrates non-inferior sedation success when compared to midazolam while offering a superior recovery profile and improved postoperative safety. These findings indicate that remimazolam may serve as a more advantageous sedative option for outpatient dental procedures, especially in environments requiring rapid patient turnover. Trial registration The trial was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2100050822, URL: https://www.chictr.org.cn/showproj.html?proj=133251 , Principal investigator: Hui Zhang, date of registration: September 4, 2021).