Original Research INTERVENTIONAL PULMONOLOGY
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* Gerard A. Silvestri, MD, FCCP; Brad D. Vincent, MD, FCCP; Momen M. Wahidi, MD, FCCP; Emory Robinette, MD, FCCP; James R. Hansbrough, MD, FCCP; and Gordon H. Downie, MD, PhD, FCCP
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 > 18 years of age were randomized (2:3) to receive fospropofol, 2 mg/kg or 6.5 mg/kg, after pretreatment with fentanyl, 50 !g. 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 < 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. Trial registration: Clinical Trials.gov Identifier: NCT00306722 (CHEST 2009; 135:41– 47) Key words: bronchoscopy; conscious sedation; fospropofol disodium Abbreviations: AE ! adverse event; ASA ! American Society of Anesthesiologists; HVLT-R ! Hopkins Verbal Learning Test-Revised; MOAA/S ! Modified Observer’s Assessment of Alertness/Sedation
ver 500,000 flexible bronchoscopies are perO formed yearly in the United States. Sedative 1
medications decrease bronchoscopy-related anxiety, For editorial comment see page 4
pain, oropharyngeal irritation, cough, and chest discomfort, thus increasing the tolerability of the procedure.2–6 Benzodiazepines combined with opioids are the most frequently used sedative agents.7,8 Benzodiazepines may produce prolonged sedation and cogni-
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