Clinical efficacy and safety of fluticasone propionate 1 mg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with severe asthma

A randomized, double-blind, cross-over study was conducted to assess the efficacy and safety of fluticasone propionate 1 mg twice daily administered via a pressurized metered dose inhaler (pMDI) containing the new non-chlorofluorocarbon (CFC) propellant (HFA 134a), or the established CFC propellants 11 and 12 in patients with severe asthma. The study comprised a 2-week run-in period followed by two 6-week treatment periods, with no washout period in between. One hundred and nineteen symptomatic adult patients with severe asthma, who were receiving inhaled beclomethasone 2–4 mg day−1 or equivalent, were randomized to treatment.Patients were randomized to one of two sequence groups (sequence 1: HFA 134a pMDI then CFC pMDI or sequence 2: CFC pMDI then HFA 134a pMDI). The sequence groups differed with respect to mean peak expiratory flow (PEF) at baseline; however, the magnitude of the increase in PEF from baseline during treatment was similar in the two sequence groups. Mean PEF at baseline was 334 l min−1 in sequence group 1 (HFA 134a→CFC pMDI) and this increased to 357 l min−1 and 366 l min−1 during treatment with the HFA 134a and CFC pMDI, respectively. In sequence group 2 (CFC→HFA 134a pMDI) mean PEF at baseline was 297 l min−1 and this increased to 336 l min−1 and 328 l min−1 during treatment with the HFA 134a and CFC pMDI, respectively.Based on an overall analysis of the two treatment groups at week 6, equivalence was demonstrated; the mean treatment difference (HFA 134a-CFC pMDI) in morning PEF was 0 l min−1 (90% confidence interval (CI), for difference between groups: −7, 6 l min−1). There was a comparable improvement in secondary efficacy variables, including clinic lung function measurements, in the two treatment groups. The incidence and type of most adverse events were similar in the two treatment groups. There was no difference in the adjusted geometric mean morning serum cortisol levels after treatment with the HFA 134a and CFC pMDI.Therefore, the fluticasone propionate HFA 134a pMDI constitutes a suitable replacement for the established CFC pMDI at a microgram equivalent dose