Study objectives: The primary objective was to determine whether high-dose formoterol, 24 mug bid, was associated with more asthma exacerbations compared with lower formoterol doses in patients with stable persistent asthma. Serious asthma exacerbations (life threatening or requiring hospitalization) were the primary end point. Secondary end points included significant exacerbations requiring systemic corticosteroids, all exacerbations, and changes in FEV1.
Design: In a multicenter, placebo-controlled, parallel-group study, patients were randomized to 16 weeks of treatment with formoterol, 24 microg bid; formoterol, 12 microg bid, with up to two additional 12-microg doses daily on demand for worsening symptoms (12 microg bid plus on demand); formoterol, 12 microg bid; or placebo. The formoterol 12-microg-bid plus on-demand regimen was administered open label, while the other three regimens were double blind.
Setting: Outpatient clinics.
Patients: A total of 2,085 patients aged > or = 12 years with stable, persistent asthma were enrolled and treated; 65% (n = 1,347) received regular concomitant antiinflammatory therapy during the study.
Measurements and results: Nine patients had respiratory-related serious adverse events (SAEs) requiring hospitalization: two patients (0.4%) in the 24-microg-bid group; one patient (0.2%) in the 12-microg-bid plus on-demand group; five patients (0.9%) in the 12-microg-bid group; and one patient (0.2%) in the placebo group. All of these events were asthma related, except for two SAEs in the 12-microg-bid group that were later considered not to be asthma related by independent reviewers who were not associated with the conduct of the study. The proportions of patients with significant asthma exacerbations (requiring systemic corticosteroids) were similar in the 24-microg-bid group (6.3%, 33 of 527 patients), 12-microg-bid group (5.9%, 31 of 527 patients) and placebo group (8.8%, 45 of 514 patients) and lower in the 12-microg-bid plus on-demand group (4.4%, 23 of 517 patients; p = 0.0057 vs placebo). All treatments were well tolerated. All formoterol treatment regimens had a significant effect on FEV1 measured 2 h after dose during the study (p < 0.0001 vs placebo); and on predose trough FEV1 measured at all visits after baseline (p < 0.002 vs placebo).
Conclusions: Treatment with formoterol, 24 microg bid, was not associated with an increase in serious asthma exacerbations compared with the lower formoterol doses or placebo.