Study objectives: To compare the efficacy of
adding formoterol or salbutamol to regular ipratropium bromide
treatment in COPD patients whose conditions were suboptimally
controlled with ipratropium bromide alone.
randomized, double-blind, double-dummy, two-period, crossover clinical
Setting: Twenty-four clinics and university
medical centers in nine countries.
hundred seventy-two patients with baseline FEV1 ≤ 65%
predicted, with FEV1 reversibility to salbutamol not
exceeding the normal variability of the measurement, and symptomatic
despite regular treatment with ipratropium bromide.
Interventions: Each patient received two treatments in
random order: either inhaled formoterol dry powder, 12 μg bid, in
addition to ipratropium bromide, 40 μg qid for 3 weeks, followed by
salbutamol, 200 μg qid, in addition to ipratropium, 40 μg qid for 3
weeks, or vice versa.
Measurements and results:
Efficacy end points included morning premedication peak expiratory flow
(PEF) during the last week of treatment (primary end point), the area
under the curve (AUC) for FEV1 measured for 6 h after
morning dose on the last day of treatment, and symptom scores (from
daily diary recordings). Morning PEF and the AUC for FEV1
were significantly better for formoterol/ipratropium than for
salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively).
The formoterol/ipratropium combination also induced a greater
improvement in mean total symptom scores (p = 0.0042). The safety
profile of the two treatments was comparable.
Conclusions: In COPD patients requiring combination
bronchodilator treatment, the addition of formoterol to regular
ipratropium treatment is more effective than the addition of