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

Chest. 2001 May;119(5):1347-56. doi: 10.1378/chest.119.5.1347.


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 FEV(1) < or = 65% predicted, with FEV(1) 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 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg 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 FEV(1) 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 FEV(1) 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albuterol / administration & dosage*
  • Bronchodilator Agents / administration & dosage*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ethanolamines / administration & dosage*
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate
  • Humans
  • Ipratropium / administration & dosage*
  • Lung Diseases, Obstructive / complications
  • Lung Diseases, Obstructive / drug therapy*
  • Lung Diseases, Obstructive / physiopathology
  • Male
  • Middle Aged
  • Peak Expiratory Flow Rate
  • Vital Capacity


  • Bronchodilator Agents
  • Ethanolamines
  • Ipratropium
  • Albuterol
  • Formoterol Fumarate