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 μg/FEN 50 μg per actuation) via a spacer (Aerochamber®) (MDI 40/100). Patients (n = 535) were then randomized to: Respimat® SMI containing IB 10 μg/FEN 25 μg (Respimat® SMI 10/25), IB 20 μg/FEN 50 μg (Respimat® SMI 20/50), one actuation tid or CFC‐MDI containing IB 20 μg/FEN 50 μg per actuation (in total 1B 40 μg/FEN 100 μg), 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 (FEV 1 ) 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. Pediatr Pulmonol. 2004; 37:264–272. © 2004 Wiley‐Liss, Inc.