Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD.
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 microg qd, plus formoterol, 12 microg bid, to salmeterol, 50 microg bid, plus fluticasone, 500 microg 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 FEV(1) area under the curve for the time period 0 to 12 h (AUC(0-12)) and peak FEV(1).


RESULTS
A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV(1), 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 FEV(1) 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 FEV(1), 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV(1) and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV(1) 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.


BACKGROUND
Clinicaltrials.gov Identifier: NCT00239421.
Rabe
Klaus F
KF
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: k.f.rabe@lumc.nl.
Timmer
Wolfgang
W
Boehringer Ingelheim Pharma, Ingelheim, Germany.
Sagkriotis
Alexandros
A
Boehringer Ingelheim Pharma, Ingelheim, Germany.
Viel
Klaus
K
Boehringer Ingelheim Pharma, Ingelheim, Germany.
D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
D000730:Androstadienes; D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide