Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat Soft Mist Inhaler vs. a conventional metered dose inhaler plus spacer in children with asthma.

The objective of this study was to compare the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN; Berodual) delivered from the novel propellant-free Respimat Soft Mist Inhaler (SMI) with that from a chlorofluorocarbon (CFC) metered-dose inhaler (MDI) plus spacer in children with asthma. The study followed a multicenter, randomized, double-blind (within Respimat SMI), parallel-group design. During the 2-week run-in period, patients received two actuations of CFC-MDI tid (IB 20 microg/FEN 50 microg per actuation) via a spacer (Aerochamber) (MDI 40/100). Patients (n=535) were then randomized to: Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50), one actuation tid or CFC-MDI containing IB 20 microg/FEN 50 microg per actuation (in total 1B 40 microg/FEN 100 microg), or two actuations tid via Aerochamber (MDI 40/100), for 4 weeks. The primary endpoint was the change in forced expiratory volume in 1 second (FEV1) during the first 60 min after dosing (area under the curve from 0-1 h [AUC(0-1 h)]) on day 29. Analysis of the primary endpoint demonstrated that the efficacy of Respimat SMI 10/25 and 20/50 was equivalent to or greater than that of MDI 40/100. Similar results indicating that Respimat SMI 10/25 and 20/50 were not inferior to MDI 40/100 were also found on days 1 and 15. Analyses of other secondary endpoints supported these results. The safety profile of Respimat SMI was comparable to that of the CFC-MDI plus spacer. In conclusion, IB/FEN delivered via Respimat SMI is at least as effective as, and is as safe as, when delivered via CFC-MDI plus Aerochamber in children with asthma. Use of Respimat SMI thus enables a 2-4-fold reduction in the nominal dose of IB/FEN, and obviates the need for a spacer.

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.

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

AIMS: Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). METHODS: In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). RESULTS: Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. CONCLUSION: Compared with placebo, tiotropium improved lung function in patients with mild COPD.