A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy

• Published in: Chest Vol. 135; no. 1; p. 41
• Main Authors: Silvestri, Gerard A, Vincent, Brad D, Wahidi, Momen M, Robinette, Emory, Hansbrough, James R, Downie, Gordon H
• Format: Journal Article
• Language: English
• Published: United States 01.01.2009
• Subjects: Adult; Aged; Aged, 80 and over; Bronchoscopes; Bronchoscopy; Conscious Sedation; Double-Blind Method; Female; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - adverse effects; Injections, Intravenous; Male; Middle Aged; Patient Satisfaction; Propofol - administration & dosage; Propofol - adverse effects; Propofol - analogs & derivatives; Treatment Outcome; Young Adult
• ISSN: 1931-3543
• DOI: 10.1378/chest.08-0623

Fospropofol disodium is a water-soluble prodrug of propofol with unique pharmacokinetic/pharmacodynamic properties. This randomized, double-blind, multicenter study evaluated the use of fospropofol in patients undergoing flexible bronchoscopy. Patients >or= 18 years of age were randomized (2:3) to receive fospropofol, 2 mg/kg or 6.5 mg/kg, after pretreatment with fentanyl, 50 microg. Supplemental doses of each were given per protocol. The primary end point was sedation success, which was defined as follows: three consecutive Modified Observer's Assessment of Alertness/Sedation scores of <or= 4 plus procedure completion without alternative sedative medication and/or mechanical ventilation. Other end points included treatment success, patient/physician satisfaction, and safety. Of 252 patients, 150 were randomized to receive 6.5 mg/kg fospropofol; 102 were randomized to receive 2 mg/kg fospropofol. Sedation success rates were 88.7% and 27.5%, respectively (p < 0.0001). Treatment successes (91.3% vs 41.2%, respectively; p < 0.001), willingness to be treated again (94.6% vs 78.2%, respectively; p < 0.001), and absence of procedural recall (83.3% vs 55.4%, respectively; p < 0.001) were significantly better with the administration of 6.5 mg/kg fospropofol. The median time to full alertness was slightly longer for the 6.5 mg/kg dose (5.5 vs 3.0 min, respectively). The proportion of patients requiring supplemental therapy with analgesics (16.7% vs 37.3%, respectively) and the use of alternative sedative medications (8.0% vs 58.8%, respectively) were lower for patients in the 6.5 mg/kg dose group (all comparisons, p < 0.001). The most frequent adverse events (AEs) were transient and self-limited paresthesias and pruritus of mild-to-moderate severity. Hypoxemia (predominantly mild-to-moderate) was the most common sedation-related AE, and occurred in 15.4% and 12.6% of patients, respectively, in the 6.5 and 2 mg/kg fospropofol dose groups. Fospropofol provided safe and effective sedation for patients undergoing flexible bronchoscopy. Clinical Trials.gov Identifier: NCT00306722.