Proventil HFA Provides Bronchodilation Comparable to Ventolin Over 12 Weeks of Regular Use in Asthmatics

¹ From the Department of Medicine, University of Maryland, Baltimore
² From the National Jewish Medical and Research Center, Denver
³ From the UCSD Medical Center, San Diego
⁴ From the 3M Pharmaceuticals, St. Paul, Minn.

Objective: To compare the bronchodilator effectiveness of albuterol reformulated 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-dummy, parallel group, placebo-controlled, multicenter trial of asthmatics requiring inhaled β-adrenergic bronchodilators for symptom control.

Interventions: Treatment qid with Proventil HFA, Ventolin, or HFA-134a placebo for 12 weeks.

Measurements: At weeks 0, 4, 8, and 12, spirometry was performed predose and serially over 6 h after dosing with study drug. Bronchodilator efficacy variables, based on FEV₁ response to 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 characteristics were similar for patients randomized to Proventil HFA (193), Ventolin (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 spirometry, at weeks 0, 4, 8, and 12. For all efficacy variables, except time to onset of effect, the Proventil HFA and Ventolin results were significantly greater than placebo. Time to onset of effect for the HFA-134a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results were found to be consistent across subgroup analyses of inhaled and nasal corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, weight (<60, 60 to 100, and >100 kg), and baseline FEV_l (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 comparable to Ventolin and superior effects to HFA-134a placebo over 12 weeks of regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use.

Key Words: albuterol • asthma • HFA-134a propellant

Submitted on March 18, 1997
Accepted on July 28, 1000

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