Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD.
OBJECTIVE
To compare the efficacy, tolerability, and safety of therapy with formoterol and oral slow-release theophylline (THEO) in patients with COPD.


METHODS
A randomized, parallel-group study, with double-blind arms for formoterol and placebo (PL) and an open arm for oral slow-release THEO administered in individual doses on the basis of plasma concentrations.


METHODS
Eighty-one centers worldwide.


METHODS
Eight hundred fifty-four patients with symptomatic COPD.


METHODS
Comparison of twice-daily inhaled formoterol dry powder (12 or 24 microg), PL, and THEO (individualized doses) over 12 months.


RESULTS
Compared to PL, doses of formoterol and THEO both significantly improved the area under the curve for FEV(1) measured over a period of 12 h following the morning dose of study medication at 3 and 12 months (p < 0.001 for all comparisons). Therapy with formoterol, 12 microg, was significantly more effective than that with THEO (p < or = 0.026). Formoterol significantly reduced the percentage of "bad days" (i.e., days with at least two individual symptom scores > or = 2 and/or a reduction in peak expiratory flow from a baseline of > 20%; p < or = 0.035 vs. PL and THEO), and the use of salbutamol rescue medication (p < or = 0.003 vs PL) over the whole treatment period, while the effect of THEO was similar to that of PL. Therapy with formoterol and THEO was more effective than PL at improving quality of life for > 12 months (p < or = 0.030). Treatment-related adverse events and discontinuations were more frequent among patients receiving THEO than among those receiving formoterol.


CONCLUSIONS
Long-term treatment with inhaled formoterol dry powder is more effective and better tolerated than treatment with therapeutically appropriate doses of oral slow-release THEO in symptomatic patients with COPD.
Rossi
Andrea
A
Respiratory Division, Bergamo General Hospital, Bergamo, Italy.
Kristufek
Peter
P
Levine
Bernard E
BE
Thomson
Moira H
MH
Till
Denise
D
Kottakis
John
J
Della Cioppa
Giovanni
G
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D013806:Theophylline / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D004983:Ethanolamines; D011208:Powders; D013806:Theophylline; D000068759:Formoterol Fumarate