Bronchodilator efficacy of the fixed combination of ipratropium and albuterol compared to albuterol alone in moderate-to-severe persistent asthma

Background: The potential of anticholinergics to provide bronchodilatory benefits over short-acting β₂-agonists (SABA) alone in patients with moderate-to-severe persistent asthma has not been well defined. Methods: An outpatient, randomized, double-blind, single-dose, crossover study in adult asthmatics with moderate-to-severe obstruction despite treatment with inhaled corticosteroids (ICS) was conducted comparing the fixed combination of ipratropium and albuterol (IB+ALB) to albuterol alone (ALB). Serial spirometry was performed over 6 h. SABA were withheld for 8 h, ICS and LABA for 24 h. Results: A total of 113 patients were randomized, 106 completed the study (males n=47; mean±SD age=51±13 years). Mean±SD baseline FEV₁=1.4±0.5 L (49±12% predicted). IB+ALB resulted in significantly greater improvements over ALB in the average improvement over baseline in FEV₁ as approximated from the area under the curve from 0 to 6 h after drug administration (72 ml, p<0.01) and mean peak FEV₁ response (55 ml, p<0.01) as well as higher FEV₁ responses at individual time points from 0.5 to 6 h postdose (p<0.01 for all). Time to onset of response was similar between groups but time to peak and duration of response were longer with IB+ALB versus ALB (120 versus 60 min and 245 versus 106 min, respectively). Conclusion: IB+ALB resulted in significantly greater improvement in FEV₁ and longer duration of response compared to ALB alone in patients with moderate-to-severe persistent asthma (Trial number: 1012.50; ClinicalTrial.gov NCT00096616).