A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy

Douglas Rex, Raj Bhandari, Taddese Desta, Michael P. DeMicco, Cynthia Schaeffer, Kyle Etzkorn, Charles F. Barish, Ronald Pruitt, Brooks D. Cash, Daniel Quirk, Felix Tiongco, Shelby Sullivan, David Bernstein

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and Aims: Remimazolam is an ultrashort-acting benzodiazepine. Methods: We performed a randomized double-blind comparison of remimazolam to placebo for outpatient colonoscopy. This study design was a requirement of the U.S. Food and Drug Administration. An additional group was randomized to open-label midazolam administered according to its package insert instructions (the randomization ratio for remimazolam:placebo:midazolam was 30:6:10). Study medications were administered under the supervision of the endoscopist, without any involvement of an anesthesia specialist. Patients were given 50 to 75 μg of fentanyl before receiving study medications. Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator's discretion. The primary endpoint was a composite that required 3 criteria be met: completion of the colonoscopy, no need for rescue medication, and ≤5 doses of remimazolam or placebo in any 15-minute interval (≤3 doses of midazolam in any 12-minute interval in the open-label midazolam arm). Results: There were 461 randomized patients in 12 U.S. sites. The primary endpoint was met for remimazolam, placebo, and midazolam in 91.3%, 1.7%, and 25.2% of patients, respectively (P <.0001 for remimazolam vs placebo). Patients administered remimazolam received less fentanyl, had faster recovery of neuropsychiatric function, were ready for discharge earlier, and felt back to normal sooner than patients with both placebo and midazolam. Hypotension was less frequent with remimazolam, and hypoxia occurred in 1% of patients with remimazolam or midazolam. There were no treatment-emergent serious adverse events. Conclusion: Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.)

Original languageEnglish (US)
JournalGastrointestinal Endoscopy
DOIs
StateAccepted/In press - Jan 1 2018

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Midazolam
Colonoscopy
Placebos
Safety
Recovery of Function
Fentanyl
Outpatients
remimazolam
Product Labeling
United States Food and Drug Administration
Random Allocation
Benzodiazepines
Hypotension
Anesthesia
Research Personnel
Clinical Trials

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Gastroenterology

Cite this

A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. / Rex, Douglas; Bhandari, Raj; Desta, Taddese; DeMicco, Michael P.; Schaeffer, Cynthia; Etzkorn, Kyle; Barish, Charles F.; Pruitt, Ronald; Cash, Brooks D.; Quirk, Daniel; Tiongco, Felix; Sullivan, Shelby; Bernstein, David.

In: Gastrointestinal Endoscopy, 01.01.2018.

Research output: Contribution to journalArticle

Rex, D, Bhandari, R, Desta, T, DeMicco, MP, Schaeffer, C, Etzkorn, K, Barish, CF, Pruitt, R, Cash, BD, Quirk, D, Tiongco, F, Sullivan, S & Bernstein, D 2018, 'A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy', Gastrointestinal Endoscopy. https://doi.org/10.1016/j.gie.2018.04.2351
Rex, Douglas ; Bhandari, Raj ; Desta, Taddese ; DeMicco, Michael P. ; Schaeffer, Cynthia ; Etzkorn, Kyle ; Barish, Charles F. ; Pruitt, Ronald ; Cash, Brooks D. ; Quirk, Daniel ; Tiongco, Felix ; Sullivan, Shelby ; Bernstein, David. / A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. In: Gastrointestinal Endoscopy. 2018.
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abstract = "Background and Aims: Remimazolam is an ultrashort-acting benzodiazepine. Methods: We performed a randomized double-blind comparison of remimazolam to placebo for outpatient colonoscopy. This study design was a requirement of the U.S. Food and Drug Administration. An additional group was randomized to open-label midazolam administered according to its package insert instructions (the randomization ratio for remimazolam:placebo:midazolam was 30:6:10). Study medications were administered under the supervision of the endoscopist, without any involvement of an anesthesia specialist. Patients were given 50 to 75 μg of fentanyl before receiving study medications. Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator's discretion. The primary endpoint was a composite that required 3 criteria be met: completion of the colonoscopy, no need for rescue medication, and ≤5 doses of remimazolam or placebo in any 15-minute interval (≤3 doses of midazolam in any 12-minute interval in the open-label midazolam arm). Results: There were 461 randomized patients in 12 U.S. sites. The primary endpoint was met for remimazolam, placebo, and midazolam in 91.3{\%}, 1.7{\%}, and 25.2{\%} of patients, respectively (P <.0001 for remimazolam vs placebo). Patients administered remimazolam received less fentanyl, had faster recovery of neuropsychiatric function, were ready for discharge earlier, and felt back to normal sooner than patients with both placebo and midazolam. Hypotension was less frequent with remimazolam, and hypoxia occurred in 1{\%} of patients with remimazolam or midazolam. There were no treatment-emergent serious adverse events. Conclusion: Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.)",
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AU - DeMicco, Michael P.

AU - Schaeffer, Cynthia

AU - Etzkorn, Kyle

AU - Barish, Charles F.

AU - Pruitt, Ronald

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AU - Tiongco, Felix

AU - Sullivan, Shelby

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N2 - Background and Aims: Remimazolam is an ultrashort-acting benzodiazepine. Methods: We performed a randomized double-blind comparison of remimazolam to placebo for outpatient colonoscopy. This study design was a requirement of the U.S. Food and Drug Administration. An additional group was randomized to open-label midazolam administered according to its package insert instructions (the randomization ratio for remimazolam:placebo:midazolam was 30:6:10). Study medications were administered under the supervision of the endoscopist, without any involvement of an anesthesia specialist. Patients were given 50 to 75 μg of fentanyl before receiving study medications. Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator's discretion. The primary endpoint was a composite that required 3 criteria be met: completion of the colonoscopy, no need for rescue medication, and ≤5 doses of remimazolam or placebo in any 15-minute interval (≤3 doses of midazolam in any 12-minute interval in the open-label midazolam arm). Results: There were 461 randomized patients in 12 U.S. sites. The primary endpoint was met for remimazolam, placebo, and midazolam in 91.3%, 1.7%, and 25.2% of patients, respectively (P <.0001 for remimazolam vs placebo). Patients administered remimazolam received less fentanyl, had faster recovery of neuropsychiatric function, were ready for discharge earlier, and felt back to normal sooner than patients with both placebo and midazolam. Hypotension was less frequent with remimazolam, and hypoxia occurred in 1% of patients with remimazolam or midazolam. There were no treatment-emergent serious adverse events. Conclusion: Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.)

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