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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Fospropofol provided safe and effective sedation for patients undergoing flexible bronchoscopy.


BACKGROUND
Clinical Trials.gov Identifier: NCT00306722.
Silvestri
Gerard A
GA
Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC. Electronic address: silvestri@musc.edu.
Vincent
Brad D
BD
Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC.
Wahidi
Momen M
MM
Duke University School of Medicine, Durham, NC.
Robinette
Emory
E
Pulmonary Research, Johnston Memorial Hospital, Abingdon, VA.
Hansbrough
James R
JR
Graves-Gilbert Clinic, Bowling Green, KY.
Downie
Gordon H
GH
Brody School of Medicine, East Carolina University, Greenville, NC.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020680:Bronchoscopes; D001999:Bronchoscopy; D016292:Procedural Sedation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D055815:Young Adult
D006993:Hypnotics and Sedatives; C472965:fospropofol; D015742:Propofol