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

Pediatr Pulmonol. 2004 Mar;37(3):264-72. doi: 10.1002/ppul.10428.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Bronchodilator Agents / pharmacology*
  • Child
  • Double-Blind Method
  • Drug Therapy, Combination
  • Equipment Design
  • Female
  • Fenoterol / administration & dosage
  • Fenoterol / adverse effects*
  • Fenoterol / pharmacology*
  • Humans
  • Ipratropium / administration & dosage
  • Ipratropium / adverse effects*
  • Ipratropium / pharmacology*
  • Male
  • Metered Dose Inhalers*
  • Treatment Outcome


  • Bronchodilator Agents
  • Fenoterol
  • Ipratropium