Reply

We greatly appreciate the interest of Park1 in our article2 as well as their comments. We have responded to these points here. First, Park stated that comparing remimazolam with other drugs rather than a placebo would have been better. We agree with that opinion. However, the purpose of this investigator-initiated clinical trial was to have remimazolam covered by insurance for gastrointestinal endoscopy. As a result, we demonstrated that remimazolam can be used safely at an initial dose of 3 mg and additional doses of 1 mg per dose.2-4 Until now, there have been no drugs covered by insurance in Japan5 and the usage and dosage of the drugs to be compared in gastrointestinal endoscopy were unclear, so it was not possible to compare it with benzodiazepine drugs such as midazolam or propofol. As the next step in this study, we plan a comparative study with midazolam. We conducted a retrospective study comparing this investigator-initiated clinical trial with midazolam and demonstrated high safety by shortening recovery time without increasing adverse events compared to midazolam.6 However, retrospective studies have several limitations, such as selection bias. Therefore, a multicenter prospective study of remimazolam and midazolam is planned to be conducted. Next, Park suggested that there are concerns regarding the safety of remimazolam in long-term procedures. We are also conducting investigator-initiated clinical trials to verify the efficacy and safety of remimazolam in endoscopic procedures such as endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and enteroscopy and were able to demonstrate efficacy and safety (jRCT2031220129). In conclusion, after it becomes widely used in Japan, it will be necessary to accumulate more cases and detailed evidence regarding the efficacy and safety of remimazolam. Author H.I. received honoraria for his lectures from FUJIFILM Corporation, Mitsubishi Tanabe Pharma Corporation, and Olympus Corporation. The other authors declare no conflict of interest for this article.