PROVENTIL HFA PROVIDES BRONCHODILATION COMPARABLE TO VENTOLIN OVER 12WEEKS OF REGULAR USE IN ASTHMATICS

Objective: To compare the bronchodilator effectiveness of albuterol re formulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing. Design: Randomized, double-blind, double-dum my, parallel group, placebo-controlled, multicenter trial of asthmatic s requiring inhaled beta-adrenergic bronchodilators for symptom contro l. Interventions: Treatment qid with Proventil HFA, Ventolin, or HFA-1 34a placebo for 12 weeks. Measurements: At weeks 0, 4, 8, and 12, spir ometry was performed predose and serially over 8 h after dosing with s tudy drug. Bronchodilator efficacy variables, based on FEV1 response t o study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve (AUC). Results: Demographic and baseline characterist ics were similar for patients randomized to Proventil HFA (193), Vento lin (186), and HFA-134a placebo (186). No significant differences were found between the Proventil HFA and Ventolin treatment groups for any FEV1 efficacy variable, either predose or during 6 h of serial spirom etry, at weeks 0, 4, 8, and 12. For all efficacy variables, except tim e to onset of effect, the Proventil HFA and Ventolin results were sign ificantly greater than placebo. Time to onset of effect for the HFA-13 4a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results we re found to be consistent across subgroup analyses of inhaled and nasa l corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, we ight (<60, 60 to 100, and >100 kg), and baseline FEV1 (less than or eq ual to 55% and >55% predicted). The peak FEV1 effect, duration of FEV1 effect, and AUC for FEV1 were all significantly smaller at weeks 4, 8 , and 12 than week 0 for both the Proventil HFA and Ventolin treatment groups. Conclusions: Proventil HFA provided bronchodilation comparabl e to Ventolin and superior effects to HFA-134a placebo over 12 weeks o f regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use.