PURPOSE: Fospropofol disodium (FP) is a water-soluble prodrug of propofol with unique pharmacokinetic and pharmacodynamic properties. This double-blind, multicenter study was designed to evaluate FP in patients undergoing flexible bronchoscopy.
METHODS: Patients (ASA P1 to P4, age >/=18 years) were randomly assigned at a 2:3 ratio to FP 2.0 mg/kg (low dose; LD) or FP 6.5 mg/kg (standard dose; SD), after fentanyl citrate (50 mcg). Supplemental doses of FP were given per protocol. Primary endpoint was sedation success, defined by 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores >/=4, and procedure completion without alternative sedative and/or manual/mechanical ventilation. Other endpoints included additional measures of clinical benefit and safety.
RESULTS: 252 patients were enrolled. 150 patients received FP 6.5 mg/kg; 102 patients received FP 2.0 mg/kg. 42.5% of patients were ASA P3/ P4. Sedation success rates were 88.7% for SD versus 27.5% of LD patients. Mean time to sedation was 5.7+/-4.2 minutes for SD and 14.5+/-6.5 minutes for LD. Mean time to fully alert was 8.3+/-10.1 minutes for SD and 9.1+/-15.3 minutes for LD. Supplemental analgesics were used in 16.7% of SD versus 37.3% of LD patients. Percent of patients with a MOAA/S score of <1 during the procedure was 14% in the SD group versus 6% in the LD group. Sedation-related adverse events occurred in 20.1% of SD patients compared to 12.6% of LD patients. All of these were easily managed using maneuvers commonly employed during moderate sedation. The most common treatment-related adverse reactions were perineal paresthesias, which were transient, mild and self-limiting (47.6%), pruritus (14.7%), and hypoxemia (9.9%). No drug-related serious adverse events or deaths occurred during the study. One patient with ongoing hypoxemia history in the SD group required bag valve mask ventilation.
CONCLUSION: FP 6.5 mg/kg dosing regimen is safe and effective in providing titratable sedation for flexible bronchoscopy in a patient population with significant comorbid illnesses.
CLINICAL IMPLICATIONS: FP is a promising agent for sedation in bronchoscopy.
DISCLOSURE: Brad Vincent, Grant monies (from industry related sources) This researched was funded with an unrestricted grant from MGI Pharma, Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Fospropofol Disodium is an investigational drug and is not yet FDA approved. This abstract represents preliminary findings of a Phase III investigation.