Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via Respimat((R)) Soft Misttrade mark Inhaler (SMI) versus a Pressurised Metered-Dose Inhaler in Asthma.

Objective: Respimat((R)) Soft Misttrade mark Inhaler (SMI) is a novel, propellant-free device that significantly increases lung deposition compared with pressurised metered-dose inhalers (pMDIs). The aim of this study was to compare the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN; Berodual((R))) delivered via Respimat((R)) SMI and via a chlorofluorocarbon (CFC)-driven pMDI (CFC-MDI) in patients with asthma.

Design: Multicentre, randomised, double-blind, placebo-controlled, parallel- group study.

Patients: 631 patients (18-65 years old) with stable asthma.

Interventions: After a 2-week run-in period (IB/FEN 20mug/50mug via CFC-MDI, two actuations four times a day), patients were randomised to 12 weeks' treatment with one of five treatments: IB/FEN 10mug/25mug, 20mug/50mug or placebo via Respimat((R)) SMI (one actuation four times a day), or IB/FEN 20mug/50mug or placebo via CFC-MDI (two actuations four times a day). The main efficacy measure was lung function (assessed on days 1, 29, 57 and 85); safety was assessed by monitoring adverse events.

Results: Bronchodilator responses to IB/FEN were much greater than those to placebo (mean peak increases in forced expiratory volume in 1 second [FEV(1)] on day 85: 0.498-0.521L, active treatment; 0.215 and 0.240L, placebo). According to the primary endpoint, i.e. the average change in FEV(1) from test-day baseline over the 6 hours after dosing on day 85, neither IB/FEN dosage via Respimat((R)) SMI was inferior to IB/FEN via pMDI (p < 0.001). Non-inferiority of the two Respimat((R)) SMI dosages was supported by analyses of other lung function measures, e.g. average change in FEV(1) from test-day baseline over the 6 hours after dosing on the other 3 test days, and peak FEV(1) on all test days. Overall, the safety profile of IB/FEN via Respimat((R)) SMI was comparable to that via CFC-MDI.

Conclusion: IB/FEN from Respimat((R)) SMI is as effective and safe as from CFC-MDI and enables a 2- to 4-fold daily dose reduction of IB/FEN.