title: A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations.
abstract: Fospropofol is a sedative hypnotic with a slower onset and longer duration of action. Fospropofol has demonstrated successful dose-dependent sedation at 6.5 mg/kg. This study evaluated the efficacy and safety of a lower weight-adjusted dose compared with the approved dose (4.875 or 6.5 mg/kg depending on patient subgroup) in high-risk elderly patients undergoing colonoscopy. In this study, 153 subjects were classified into 3 subgroups based on the following: age, weight, and American Society of Anesthesiologist (ASA) physical status criteria. The patients were randomized to the approved dose or weight-adjusted dose of fospropofol in a 1:1 ratio. Subgroup 1 (n = 50) consisted of patients weighing <60 kg, age 18-65 years, and ASA I or II; subgroup 2 (n = 50) consisted of patients weighing <60 kg; age 65 years and above, and ASA I-IV; and subgroup 3 (n = 53) consisted of patients weighing ≥60 kg, age 65 years and above, and ASA I-IV. Sedation, modified sedation and treatment success, and safety parameters were assessed. The approved dose had a significantly higher sedation success compared with the weight-adjusted dose: 96% versus 72% for subgroup 1; 84% versus 72% for subgroup 2; and 96% versus 67.9% for subgroup 3. There was a decreased need for alternative sedatives in subgroups 1 and 3 and fewer sedation- and treatment-emergent adverse events in all the subgroups for the approved dose. Additionally, sedation success data pooled across subgroups and examined based on age, weight, and ASA categories showed a significantly higher rate of sedation success in the approved dose arm across all the subgroups. The rate of sedation, modified sedation, and treatment success were higher in patients administered the approved dose for all the subgroups. No clinically significant advantage was demonstrated using a lower modified dose in this study population. The approved dose is recommended in the elderly, more obese, and high-risk patients when used for moderate sedation.
authors: Department of Anesthesiology and Neurological Surgery, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA. sergio.bergese@osumc.edu
authors: Sergio D
authors: SD
authors: Bergese
authors: Poorvi
authors: P
authors: Dalal
authors: Rashmi
authors: R
authors: Vandse
authors: Andrew
authors: A
authors: Satlin
authors: Zhengning
authors: Z
authors: Lin
authors: Keith
authors: K
authors: Candiotti
authors: Larry
authors: L
authors: Cohen
authors: Tong-Joo
authors: TJ
authors: Gan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001835:Body Weight; D003113:Colonoscopy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; C472965:fospropofol; D015742:Propofol