Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non‐inferiority, phase III trial

Abstract

Background and Aim Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. Methods This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. Results The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). Conclusion This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

Efficacy and Safety of Remimazolam in Endoscopic Sedation—A Systematic Review and Meta-Analysis

“…Remimazolam has been studied for use in sedation for endoscopic procedures such as gastroscopy, colonoscopy, and bronchoscopy. Several original studies have shown that remimazolam facilitates faster onset and recovery, has higher sedative efficacy than midazolam, and is associated with lower incidence of hypotension and hypoxemia when compared with propofol (13,14). This is consistent with the results of our meta-analysis, and this indicates that remimazolam has a better safety profile for sedation for endoscopic procedures.…”

“…Seven studies involving a total of 1,996 patients were included, and all of them were RCTs (published April 2005-Jan 2021); four involved 1,079 patients undergoing colonoscopy (13,(21)(22)(23), two involved 478 patients undergoing upper gastrointestinal endoscopy (14,20), and one involved 439 patients undergoing bronchoscopy (12). The age of the patients ranged from 18 to 95 years, and male patients accounted for 45.38% (Table 1).…”

“…Compared with midazolam, remimazolam has the advantages of rapid onset, rapid recovery, and a higher safety profile (12,13). Previous studies have found that remimazolam has the same success rate of sedation as propofol but is associated with a lower incidence of hypotension and hypoxemia, and faster awakening time when used for endoscopic sedation (14). However, it is a new drug, and its efficacy and safety for endoscopic sedation have not been established.…”

Sedation outcomes for remimazolam, a new benzodiazepine

“…Furthermore, as compared with propofol, remimazolam was significantly associated with a lower risk of pain on injection (P < 0.001), a lower risk of bilirubin elevation (P = 0.019), a higher respiratory rate (P < 0.001), and higher SpO 2 (P < 0.001) [19]. In a comparison of a remimazolam group and propofol group, the incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower in the remimazolam group [20].…”

Efficacy and Safety of Remimazolam Besylate Versus Propofol during Hysteroscopy: Single‐centre Randomized Controlled Trial

“…In another multicentre phase III trial, researchers also found that remimazolam (5.75 min) yielded a faster recovery from sedation than propofol did (6.71 min). This is a potential bene t of remimazolam over propofol [22]. It can be speculated that both remimazolam and propofol can meet the required sedation depth and maintenance time for uterine cavity examination but that the sedation of remimazolam can avoid the phenomenon of deep sedation in the propofol group and has little effect on the inhibition of the central nervous system of patients.…”