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 (AUC0–12) 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 AUC0–12, 78 mL [p = 0.0006]; mean difference in FVC AUC0–12, 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.