PURPOSE: Indacaterol is a novel, inhaled, once-daily long-acting β2-agonist for COPD. This study was designed to demonstrate that indacaterol has a similar, and potentially superior, efficacy profile to the once-daily anticholinergic bronchodilator, tiotropium.
METHODS: In a blinded, double-dummy study, patients with moderate-to-severe COPD were randomized to 12 weeks’ treatment with once-daily indacaterol 150 μg or tiotropium 18 μg. The primary objective was to demonstrate non-inferiority of indacaterol to tiotropium for trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose measurements) after 12 weeks. Also assessed were rescue albuterol use over 12 weeks, transition dyspnea index (TDI) and health status (St George's Respiratory Questionnaire, SGRQ) at 12 weeks, and adverse events.
RESULTS: 1598 patients (mean age 63.5 years; post-bronchodilator FEV1 54.5% predicted, FEV1/FVC 51.1%) were randomized; 1477 (92%) completed. Trough FEV1 at 12 weeks (baseline-adjusted) was 1.44 L with indacaterol and 1.43 L with tiotropium (p<0.001 for non-inferiority); unadjusted increases from baseline were, respectively, 130 and 120 mL.
Indacaterol-treated patients used less rescue albuterol compared with tiotropium (least squares mean [LSM] changes from baseline of –1.40 versus −0.85 puffs/day, p<0.001) and had a higher percentage of days without rescue use (LSM 46.1 versus 41.4, p=0.004). Dyspnea improved from baseline significantly more with indacaterol than with tiotropium (LSM TDI total scores 2.01 and 1.43 respectively; p<0.001). SGRQ scores demonstrated significantly better health status with indacaterol than with tiotropium (raw mean changes from baseline −5.1 versus −3.0; treatment contrast p<0.001 by analysis of covariance).
Adverse events were reported for 39.7% and 37.2% of patients receiving indacaterol and tiotropium, respectively, and serious adverse events for 2.8% and 3.8%, respectively.
CONCLUSION: Both bronchodilators demonstrated spirometric efficacy. Once-daily indacaterol was superior to tiotropium for clinical outcomes, with significantly greater improvements in dyspnea, use of rescue albuterol and health status. The incidence of adverse events was similar between the treatments.
CLINICAL IMPLICATIONS: Indacaterol is an effective and well-tolerated once-daily bronchodilator, with clinical advantages over tiotropium as a maintenance bronchodilator for patients with COPD.
DISCLOSURE:This study (ClinicalTrials.gov Identifier: NCT00900731) did not complete until after the general abstract submission deadline. Grant monies (from sources other than industry): Roland Buhl: Deutsche Forschungsgemeinschaft (DFR, German Research Foundation; www.dfg.de) Grant monies (from industry related sources): Roland Buhl/Mainz University Hospital have received financial compensation for services as part of clinical trials Employee: Cheryl Lassen, Michelle Henley and Benjamin Kramer are employees of the study sponsor, Novartis Consultant fee, speaker bureau, advisory committee, etc: Roland Buhl has received fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Nycomed and Pfizer Other: This study was sponsored by Novartis Pharma AG. Product/procedure/technique that is considered research and is NOT yet approved for any purpose: Indacaterol is an investigational drug that has not yet been approved for the treatment of COPD.