Improved delivery of ipratropium bromide/fenoterol from Respimat® Soft Mist™ Inhaler in patients with COPD

We performed a multicentre, randomised, double-blind (within-device), placebo- and active-controlled, parallel-group study to compare the efficacy and safety of ipratropium bromide plus fenoterol hydrobromide (IB/FEN; Berodual(R)) delivered via the novel, propellant-free Respimat(R) Soft Mist(TM) Inhaler (SMI) and from a chlorofluorocarbon (CFC)-metered-dose inhaler (MDI) in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. After 2-weeks' run-in (CFC-MDI [IB 20 mug/FEN 50 mug per actuation] two actuations q.i.d. [MDI 40/100]), 892 patients were randomised to Respimat(R) SMI containing IB 10 mug/FEN 25 mug (Respimat(R) SMI 10/25), IB 20 mug/FEN 50 mug (Respimat(R) SMI 20/50) or placebo (one actuation q.i.d.), or a CFC-MDI containing IB 20 mug/FEN 50 mug (MDI 40/100) or placebo (two actuations q.i.d.) for 12 weeks. Analysis of the primary endpoint (change in forced expiratory volume in 1 s [FEV1] in the first 60 min after dosing [area under the curve; AUC(0-1h)]) on day 85 showed that the efficacy of Respimat(R) SMI 20/50 (but not Respimat(R) SMI 10/25) was not inferior to that of MDI 40/100. The safety profile of Respimat(R) SMI was comparable to CFC-MDI. Switching from MDI 40/100 to Respimat(R) SMI was well tolerated. Respimat(R) SMI enables a 50% reduction of the nominal inhaled dose of IB/FEN in COPD patients white offering similar therapeutic efficacy and safety to the CFC-MDI. (C) 2004 Published by Elsevier Ltd.