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 beta(2)-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 6h. SABA were withheld for 8h, ICS and LABA for 24h. RESULTS: A total of 113 patients were randomized, 106 completed the study (males n=47; mean+/-SD age=51+/-13 years). Mean+/-SD baseline FEV(1)=1.4+/-0.5 L (49+/-12% predicted). IB+ALB resulted in significantly greater improvements over ALB in the average improvement over baseline in FEV(1) as approximated from the area under the curve from 0 to 6h after drug administration (72 ml, p<0.01) and mean peak FEV(1) response (55 ml, p<0.01) as well as higher FEV(1) responses at individual time points from 0.5 to 6h 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 FEV(1) and longer duration of response compared to ALB alone in patients with moderate-to-severe persistent asthma (Trial number: 1012.50; ClinicalTrial.gov NCT00096616).