title: A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy.
abstract: OBJECTIVE
  Remimazolam is an ultra-short-acting benzodiazepine currently being developed for procedural sedation and for induction and maintenance of anesthesia. This trial was the fourth study for procedural sedation. The aim was to compare the safety and efficacy profile of remimazolam and to refine suitable doses for subsequent phase III studies in this indication.
  
  
  METHODS
  This was a randomized, double-blind, parallel group, active controlled clinical trial with 162 male and female patients, aged 18 to 70, scheduled to undergo a routine colonoscopy. Patients were randomized to receive 1 of 3 remimazolam doses or midazolam for sedation. Supplemental oxygen and 100 μg of fentanyl was given before procedures were started, and the colonoscopy commenced as soon as suitable sedation had been achieved (Modified Observer's Assessment of Alertness/Sedation score ≤3). Top-up doses of the study drug and/or fentanyl were allowed to maintain suitable sedation and/or analgesia. Response was defined as sufficient sedation, no rescue sedative, and no ventilation required.
  
  
  RESULTS
  This study showed that a single dose of remimazolam or midazolam, followed by top-up doses to maintain suitable sedation, provided adequate sedation with a high success rate (>92%) for the remimazolam groups, compared with 75% for the midazolam group (P = .007). There was no requirement for mechanical ventilation in any group, and procedure failures were all due to use of rescue sedative.
  
  
  CONCLUSIONS
  The high success rates and good safety profile of remimazolam observed in this study warrants further investigation and confirmation in phase III trials. (
  
  
  BACKGROUND
  NCT01145222.).
authors.affiliation: Charlottesville Medical Research, Charlottesville, Virginia, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pambianco
authors.affiliation: PAION UK Ltd, Cambridge, United Kingdom.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Borkett
authors.affiliation: Advanced Clinical Research Institute, Anaheim, California, USA.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Riff
authors.affiliation: Advanced Clinical Research Institute, Anaheim, California, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Winkle
authors.affiliation: Miami Research Institute, Miami, Florida, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Schwartz
authors.affiliation: Helen Keller Hospital, Sheffield, Alabama, USA.
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Melson
authors.affiliation: PAION Deutschland GmbH, Aachen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Wilhelm-Ogunbiyi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D003113:Colonoscopy; D054810:Deep Sedation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008874:Midazolam / Q000009:adverse effects; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C522201:remimazolam; D008874:Midazolam