Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD.
OBJECTIVE
Current guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD.


METHODS
COPD patients (mean FEV(1) 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15microg BID [n=76] or tiotropium 18microg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15microg BID and tiotropium 18microg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes.


RESULTS
Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values <0.005). Peak FEV(1), peak FVC, 24-h trough FEV(1), and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events.


CONCLUSIONS
In this study, the combination of nebulized arformoterol 15microg BID plus tiotropium 18microg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.
Tashkin
D P
DP
David Geffen School of Medicine UCLA, Los Angeles, CA 90095-1690, USA. dtashkin@mednet.ucla.edu
Donohue
J F
JF
Mahler
D A
DA
Huang
H
H
Goodwin
E
E
Schaefer
K
K
Hanrahan
J P
JP
Andrews
W T
WT
D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity
D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide