In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium: A 3-week, randomized, double-blind, within-patient, multicenter study

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. Design: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. Setting: Twenty-four clinics and university medical centers in nine countries. Patients: One 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 salbutamol.