Remimazolam safe, effective for outpatient colonoscopy sedation
LAS VEGAS — Remimazolam was a safe and effective agent for conscious sedation during outpatient colonoscopy in a multicenter randomized controlled trial, according to data presented at ACG 2016.
Remimazolam (Paion) is a novel, ultra-short acting benzodiazepine with potential benefits for use in procedural sedation.
Douglas K. Rex
“Remimazolan is modified with a carboxylic ester linkage so that it is metabolized by non-specific tissue esterases and has an elimination half-life of 45 minutes,” Douglas K. Rex, MD, MACG, from Indiana University Hospital, said during his presentation. “The purpose of this study was to evaluate the efficacy and safety of remimazolam for colonoscopy.”
Rex and colleagues randomly assigned 461 colonoscopy patients (mean age, 54.5 years; 52.5% women; ASA class I-III) recruited from 13 sites in the U.S. to receive remimazolam (n = 298; 5 mg initial dose, 2.5 mg top-up doses), placebo (n = 60) or open-label midazolam (n = 103). All participants also received an initial dose of 50 mg to 75 mcg fentanyl, and all the agents were administered by the endoscopist or under their supervision without an anesthesiologist.
Colonoscopy completion without requirement of alternative sedative and no more than a defined number of additional doses served as the composite primary endpoint.
Successful colonoscopy occurred in significantly more participants who received remimazolam (91.3%) compared with placebo (1.7%) and midazolam (25%). For individual components of the composite score, procedure completion was achieved in almost all of the patients in all three groups, while adequate sedation was achieved in 94% of the remimazolam group, 27% of the placebo group and 46% of the midazolam group, and the requirement of not receiving any rescue medication was achieved in 97%, 5% and 35%, respectively.
Fentanyl dosing was lower with remimazolam, with a mean dose of 89 mcg, which was 17% lower than mean dose for midazolam, and there were 44% lower total numbers of fentanyl doses.
Time to reach adequate sedation was 3.5 to 4 minutes in the remimazolam group, and the mean time to full alertness was 7.2 minutes, which was 54% lower than with midazolam. Time to patient assessment of feeling “completely normal” was 39% lower with remimazolam than with midazolam. Neuropsychiatric recovery based on the Hopkins verbal learning test was also faster with remimazolam.
Treatment emergent adverse events were 19% lower with remimazolam vs. midazolam, and the difference was largely accounted for by differences in hypotension (44% vs. 67%). Hypoxia incidence was 1% in both groups. No treatment-emergent serious adverse events occurred.
“Remimazolam given under the supervision of an endoscopist is a safe and effective sedative for use in colonoscopy patients with short recovery times and fast restoration of neuropsychiatric function,” Rex said. – by Adam Leitenberger
Rex DK, et al. Abstract #45. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 17-19, 2016; Las Vegas, NV.
Disclosures: Rex reports he serves on the advisory committee or board for Colonary Concepts, is a consultant for Boston Scientific, Ironwood Pharmaceuticals, Novo Nordisk Inc. and Olympus, and has received grant/research support from Boston Scientific, Covidien/Medtronic, EndoAid, EndoChoice, Olympus and Paion.