Study objective: To compare the efficacy and safety of
ipratropium bromide reformulated with the chlorofluorocarbon (CFC)-free
propellant hydrofluoroalkane (HFA)-134a (ipratropium bromide HFA) to
that of the marketed ipratropium bromide inhalation aerosol (containing
CFC) in patients with COPD.
Design: This was a
randomized, double-blind, parallel-group, placebo-controlled,
multicenter trial. The primary efficacy parameter was acute
bronchodilator response. The primary end points were peak change in
FEV1 from baseline and area under the response-time
Setting: Thirty-one clinical centers in the
United States participated in this project.
A total of 507 patients with moderate-to-severe COPD were randomized,
and 444 patients completed the trial.
Twelve weeks of treatment four times daily with one of the following:
ipratropium bromide HFA, 42 μg; ipratropium bromide HFA, 84 μg; HFA
placebo; ipratropium bromide inhalation aerosol, 42 μg; or CFC
Measurements and results: Patients in all
active treatment groups had significant bronchodilator responses as
shown by increases in mean FEV1 from baseline of at least
15%. Bronchodilator response in all active treatment groups was also
significantly more than their respective placebo treatments based on
FEV1, area under the time-response curve from 0 to 6
h, and peak response. FVC results were similar to those seen with
FEV1. There were no significant differences in adverse
events, laboratory findings, or ECG findings among the treatment
Conclusions: Ipratropium bromide HFA, 42 μg,
provided bronchodilation comparable to the marketed ipratropium bromide
CFC, 42 μg, over 12 weeks of regular use.