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

摘要

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.nnDesign: A randomized, double-blind, double-dummy, two-period, crossover clinical trial.nnSetting: Twenty-four clinics and university medical centers in nine countries.nnPatients: 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.nnInterventions: 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.nnMeasurements 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.nnConclusions: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.