Chest
Volume 135, Issue 1, January 2009, Pages 41-47
Journal home page for Chest

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

https://doi.org/10.1378/chest.08-0623Get rights and content

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 μg. 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

Section snippets

Study Design

This was a phase 3, randomized, double-blind, dose-controlled study. The institutional review board at each study site approved the protocol. All patients provided oral and written informed consent.22

Patients

Patients ≥ 18 years of age and with an American Society of Anesthesiologists (ASA) Physical Classification System status of P1 to P4 were eligible for study enrollment. Female patients of child-bearing age had to have a negative pregnancy test result and to have used an acceptable method of birth

Patients

Twenty-four centers screened 290 patients, and 256 patients were randomized (Fig 1). Centers enrolled between 1 and 35 patients (mean, 11 patients). Four patients were eliminated from the study prior to drug administration due to abnormal laboratory test results, pharmacy delays, invalid consent, or bronchoscopy cancellation (each category, n = 1). Thus, 252 patients were included in the modified intent-to-treat population. Demographic and baseline characteristics were similar between the

Discussion

Most guidelines in the United States8, 29 and Europe30 recommend the sedation of patients when undergoing bronchoscopy. An ideal sedative should be easy to use and have a rapid onset, short duration, and quick recovery with a rapid return of cognition, as well as a predictable pharmacokinetic/pharmacodynamic profile. The most commonly used agents (benzodiazepines and opioids) have some of these properties, but each has limitations. Fospropofol may have certain advantages when compared to lipid

References (33)

  • BJ Ulmer et al.

    Propofol versus midazolam/fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists

    Clin Gastroenterol Hepatol

    (2003)
  • AM Jones et al.

    Do all patients require supplemental oxygen during flexible bronchoscopy?

    Chest

    (2001)
  • PJ Poi et al.

    Common fears of patients undergoing bronchoscopy

    Eur Respir J

    (1998)
  • GP Maguire et al.

    Patients prefer sedation for fibreoptic bronchoscopy

    Respirology

    (1998)
  • R Gonzalez et al.

    Should patients undergoing a bronchoscopy be sedated?

    Acta Anaesthesiol Scand

    (2003)
  • J Pickles et al.

    Is preparation for bronchoscopy optimal?

    Eur Respir J

    (2003)
  • Cited by (96)

    View all citing articles on Scopus

    This study was funded by a grant from MGI PHARMA, Inc (Bloomington, MN).

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    View full text