TY - JOUR
T1 - Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy
AU - PAION Investigators
AU - Pastis, Nicholas J.
AU - Yarmus, Lonny B.
AU - Schippers, Frank
AU - Ostroff, Randall
AU - Chen, Alexander
AU - Akulian, Jason
AU - Wahidi, Momen
AU - Shojaee, Samira
AU - Tanner, Nichole T.
AU - Callahan, Sean P.
AU - Feldman, Gregory
AU - Lorch, Daniel G.
AU - Ndukwu, Ikeadi
AU - Pritchett, Michael A.
AU - Silvestri, Gerard A.
N1 - Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. J. P. has received honoraria for consulting for Olympus and participated in Olympus EBUS bronchoscopy courses as an instructor. F. S. discloses that he is an employee of PAION and served as vice president of global clinical development during the trial. R. O. discloses that he is an employee of PAION and served as vice president of US medical affairs for PAION during the trial. A. C. has received research support from PAION. N. T. T. has received other grant funding from the American Cancer Society and the CHEST Foundation; received industry grant funding from Exact Sciences, Veracyte, Integrated Diagnostics, Oncimmune, Olympus, and Cook Medical; received consulting monies from Integrated Diagnostics, Olympus, Cook Medical, Veran, and Oncocyte; and participated in advisory board meetings for Veracyte. D. G. L. has served as a paid investigator for PAION. G. A. S. received grant support for this study from PAION Pharmaceuticals. None declared (L. B. Y., J. A., M. W., S. S., S. P. C., G. F., I. N., M. A. P.).
Publisher Copyright:
© 2018 American College of Chest Physicians
PY - 2019/1
Y1 - 2019/1
N2 - Background: While the complexity of flexible bronchoscopy has increased, standard options for moderate sedation medications have not changed in three decades. There is a need to improve moderate sedation while maintaining safety. Remimazolam was developed to address shortcomings of current sedation strategies. Methods: A prospective, double-blind, randomized, multicenter, parallel group trial was performed at 30 US sites. The efficacy and safety of remimazolam for sedation during flexible bronchoscopy were compared with placebo and open-label midazolam. Results: The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo arm (P <.0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner in the remimazolam arm (mean, 6.4 ± 5.82 min) compared with placebo (17.2 ± 4.15 min; P <.0001) and midazolam (16.3 ± 8.60 min). Time to full alertness after the end of bronchoscopy was significantly shorter in patients treated with remimazolam (median, 6.0 min; 95% CI, 5.2-7.1) compared with those treated with placebo (13.6 min; 95% CI, 8.1-24.0; P =.0001) and midazolam (12.0 min; 95% CI, 5.0-15.0). Remimazolam registered superior restoration of neuropsychiatric function compared with placebo and midazolam. Safety was comparable among all three arms, and 5.6% of the patients in the remimazolam group had serious treatment-emergent adverse events as compared with 6.8% in the placebo group. Conclusions: Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of action and faster neuropsychiatric recovery than midazolam.
AB - Background: While the complexity of flexible bronchoscopy has increased, standard options for moderate sedation medications have not changed in three decades. There is a need to improve moderate sedation while maintaining safety. Remimazolam was developed to address shortcomings of current sedation strategies. Methods: A prospective, double-blind, randomized, multicenter, parallel group trial was performed at 30 US sites. The efficacy and safety of remimazolam for sedation during flexible bronchoscopy were compared with placebo and open-label midazolam. Results: The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo arm (P <.0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner in the remimazolam arm (mean, 6.4 ± 5.82 min) compared with placebo (17.2 ± 4.15 min; P <.0001) and midazolam (16.3 ± 8.60 min). Time to full alertness after the end of bronchoscopy was significantly shorter in patients treated with remimazolam (median, 6.0 min; 95% CI, 5.2-7.1) compared with those treated with placebo (13.6 min; 95% CI, 8.1-24.0; P =.0001) and midazolam (12.0 min; 95% CI, 5.0-15.0). Remimazolam registered superior restoration of neuropsychiatric function compared with placebo and midazolam. Safety was comparable among all three arms, and 5.6% of the patients in the remimazolam group had serious treatment-emergent adverse events as compared with 6.8% in the placebo group. Conclusions: Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of action and faster neuropsychiatric recovery than midazolam.
KW - Modified Observer's Assessment of Alertness/Sedation Scale
KW - flexible bronchoscopy
KW - monitored anesthesia care
KW - remimazolam
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U2 - 10.1016/j.chest.2018.09.015
DO - 10.1016/j.chest.2018.09.015
M3 - Article
C2 - 30292760
AN - SCOPUS:85058685975
SN - 0012-3692
VL - 155
SP - 137
EP - 146
JO - CHEST
JF - CHEST
IS - 1
ER -