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Comparison of a Combination of Tiotropium Plus Formoterol to Salmeterol Plus Fluticasone in Moderate COPD^*

^* From the Department of Pulmonology (Dr. Rabe), Leiden University Medical Center, Leiden, the Netherlands; and Boehringer Ingelheim Pharma (Drs. Timmer and Viel, and Mr. Sagkriotis), Ingelheim, Germany.

Correspondence to: Klaus F. Rabe, PhD, MD, Department of Pulmonology C3-P, Leiden University Medical Center, Albinus-dreef 2 Postbus, NL-2300 Leiden, the Netherlands; e-mail: k.f.rabe{at}lumc.nl

Abstract

Background: A 6-week, multicenter, randomized, double-blind, parallel-group study was conducted in patients with COPD to compare lung function improvements of tiotropium, 18 µg qd, plus formoterol, 12 µg bid, to salmeterol, 50 µg bid, plus fluticasone, 500 µg bid.

Methods: Following a screening visit, subjects entered a run-in period in which they received regular ipratropium. At randomization, patients were assigned to either tiotropium plus formoterol or salmeterol plus fluticasone. After 6 weeks of treatment, a 12-h lung function profile was obtained. The coprimary end points were FEV₁ area under the curve for the time period 0 to 12 h (AUC_0–12) and peak FEV₁.

Results: A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV₁, 1.32 ± 0.43 L/min [±SD]) were included in the analysis. After 6 weeks, the 12-h lung function profiles in the group receiving tiotropium plus formoterol were superior to those in the group receiving salmeterol plus fluticasone (mean difference in FEV₁ AUC_0–12, 78 mL [p = 0.0006]; mean difference in FVC AUC_0–12, 173 mL, p < 0.0001). Also, peak responses were in favor of tiotropium plus formoterol (difference in peak FEV₁, 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV₁ and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV₁ and rescue medication use did not differ significantly between groups. Both treatments were well tolerated.

Conclusions: Tiotropium plus formoterol was superior in lung function over the day compared to salmeterol plus fluticasone in patients with moderate COPD. Long-term studies in patients with severe COPD are warranted to assess the relative efficacy of different treatment combinations.

Trial registration: Clinicaltrials.gov Identifier: NCT00239421 [ClinicalTrials.gov] .

Key Words: combination treatment • COPD • fluticasone • formoterol • lung function • salmeterol • tiotropium

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