The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD

Author(s): Hanania NA, Darken P, Horstman D, Reisner C, Lee B, et al.


Study objectives: To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting beta(2)-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD.

Design: Randomized, double-blind, multicenter, placebo-controlled study.

Setting: Seventy-six investigative sites in the United States.

Patients: Seven hundred twenty-three patients > or =40 years of age with COPD and a mean baseline FEV(1) of 42% predicted.

Interventions: FP (250 microg), SM (50 microg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks.

Measurements: Primary efficacy measures were morning predose (ie, trough FEV(1)) for FSC compared with SM and 2-h postdose FEV(1) for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures.

Results: At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p < or = 0.012) increased the morning predose FEV(1) (165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p < or = 0.001) increased the 2-h postdose FEV(1) (281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p < or = 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups.

Conclusions: Treatment with FSC (FP, 250 microg, and SM, 50 microg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.

Similar Articles

Chronic obstructive pulmonary disease surveillance - United States, 1971-2000

Author(s): Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC

Bronchodilators in chronic air-flow limitation

Author(s): Guyatt GH, Townsend M, Pugsley SO, Keller JL, Short HD, et al.

Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD

Author(s): Man WD, Mustfa N, Nikoletou D, Kaul S, Hart N, et al.

Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease

Author(s): Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, et al.

Contemporary management of chronic obstructive pulmonary disease: scientific review

Author(s): Sin DD, McAlister FA, Man SF, Anthonisen NR

Oral theophylline for chronic obstructive pulmonary disease

Author(s): Ram FS, Jones PW, Castro AA, DeBerito JA, Atallah AN, et al.

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease

Author(s): Szafranski W, Cukier A, Ramirez A, Menga G, Sansores R, et al.

Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease

Author(s): Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, et al.

Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study

Author(s): Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, et al.

Withdrawal of chronic systemic corticosteroids in patients with COPD: a randomized trial

Author(s): Rice KL, Rubins JB, Lebahn F, Parenti CM, Duane PG, et al.

Corticosteroids contribute to muscle weakness in chronic airflow obstruction

Author(s): Decramer M, Lacquet LM, Fagard R, Rogiers P

Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials

Author(s): Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, et al.

Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations

Author(s): Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, et al.

Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients

Author(s): Wongsurakiat P, Lertakyamanee J, Maranetra KN, Jongriratanakul S, Sangkaew S

Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease

Author(s): Granger R, Walters J, Poole PJ, Lasserson TJ, Mangtani P, et al.

Marked sympathetic activation in patients with chronic respiratory failure

Author(s): Heindl S, Lehnert M, Criee CP, Hasenfuss G, Andreas S

Appropriateness of domiciliary oxygen delivery

Author(s): Guyatt GH, McKim DA, Austin P, Bryan R, Norgren J, et al.

Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial

Author(s): Griffiths TL, Burr ML, Campbell IA, Lewis-Jenkins V, Mullins J, et al.

Controlled trial of oral prednisone in outpatients with acute COPD exacerbation

Author(s): Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ

Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease

Author(s): Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, et al.

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

Author(s): Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, et al.

Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis

Author(s): Jorgensen AF, Coolidge J, Pedersen PA, Peterson KP, Waldorff S, et al.