Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium.
BACKGROUND
Indacaterol is the first once-daily, long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD).


OBJECTIVE
To demonstrate greater efficacy of indacaterol versus placebo on FEV(1) 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.


METHODS
Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 microg or placebo, or open-label tiotropium 18 microg, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV(1) 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 FEV(1), 56% predicted; FEV(1)/FVC, 0.53) were randomized to the four treatment arms. Trough FEV(1) 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 microg, 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. Clinical trial registered with clinicaltrials.gov (NCT 00463567).
Donohue
James F
JF
University of North Carolina, 4125 BioInformatics Building, 130 Mason Farm Road, CB 7020, Chapel Hill, NC, USA. james_donohue@med.unc.edu
Fogarty
Charles
C
Lötvall
Jan
J
Mahler
Donald A
DA
Worth
Heinrich
H
Yorgancioglu
Arzu
A
Iqbal
Amir
A
Swales
James
J
Owen
Roger
R
Higgins
Mark
M
Kramer
Benjamin
B
D000280:Administration, Inhalation; D001786:Blood Glucose / Q000032:analysis; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000188:drug therapy; D004562:Electrocardiography; D005260:Female; D005541:Forced Expiratory Volume; D006304:Health Status; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage*; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013147:Spirometry; D000069447:Tiotropium Bromide
D001786:Blood Glucose; D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C510790:indacaterol; D011188:Potassium; D000069447:Tiotropium Bromide