The efficacy and safety of inhaled fluticasone propionate/salmeterol and ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease: an eight-week, multicenter, randomized, double-blind, double-dummy, parallel-group study

Clin Ther. 2005 May;27(5):531-42. doi: 10.1016/j.clinthera.2005.05.009.

Abstract

Background: The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components.

Objective: The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD.

Methods: We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations.

Results: Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively.

Conclusion: In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Albuterol / adverse effects
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacokinetics
  • Albuterol / therapeutic use*
  • Androstadienes / adverse effects
  • Androstadienes / pharmacokinetics
  • Androstadienes / therapeutic use*
  • Area Under Curve
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluticasone-Salmeterol Drug Combination
  • Forced Expiratory Volume / drug effects
  • Humans
  • Ipratropium / adverse effects
  • Ipratropium / therapeutic use*
  • Male
  • Middle Aged
  • Peak Expiratory Flow Rate / drug effects
  • Pulmonary Disease, Chronic Obstructive / drug therapy*

Substances

  • Androstadienes
  • Bronchodilator Agents
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • Ipratropium
  • Albuterol