Once-Daily Bronchodilators for Chronic Obstructive Pulmonary Disease Indacaterol Versus Tiotropium

Rationale. Indacaterol is the first once-daily, long-acting inhaled fir agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD). Objectives: To demonstrate greater efficacy of indacaterol versus placebo on FEV1 at 24 hours post dose (trough) after 12 weeks, to compare efficacy with placebo and tiotropium, and to evaluate safety and tolerability over 26 weeks. Measurements: Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 mu g or placebo, or open-label tiotropium 18 mu g, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV1 at 12 weeks. Additional analyses (not adjusted for multiplicity) included transition dyspnea index (TDI), health status (St George's Respiratory Questionnaire [SGRQ]), and exacerbations. Serum potassium, blood glucose, and QTc interval were measured. Results: A total of 1,683 patients (age, 63.3 yr; post-bronchodilator FEV1, 56% predicted; FEV1/FVC, 0.53) were randomized to the four treatment arms. Trough FEV1 at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium (all P < 0.001 vs. placebo). At Week 26, for indacaterol 150/300 mu g, respectively, versus placebo, TDI increased (1.00/1.18, P < 0.001) and SGRQ total score decreased (-3.3/-2.4, P < 0.01); corresponding results with tiotropium were 0.87 (P < 0.001) for TDI and (-1.0, P = not significant) for SGRQ total score. The incidence of adverse events, low serum potassium, high blood glucose, and prolonged QTc interval was similar across treatments. Conclusions: Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD.