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Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via Respimat® Soft Mist™ Inhaler (SMI) versus a Pressurised Metered-Dose Inhaler in Asthma

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Abstract

Objective

Respimat® Soft Mist™ 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®)delivered via Respimat® 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 20μg/50μg via CFC-MDI, two actuations four times a day), patients were randomised to 12 weeks’ treatment with one of five treatments: IB/FEN 10μg/25μg, 20μg/50μg or placebo via Respimat® SMI (one actuation four times a day), or IB/FEN 20μg/50μg 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 [FEV1] 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 FEV1 from test-day baseline over the 6 hours after dosing on day 85, neither IB/FEN dosage via Respimat® SMI was inferior to IB/FEN via pMDI (p < 0.001). Non-inferiority of the two Respimat® SMI dosages was supported by analyses of other lung function measures, e.g. average change in FEV1 from test-day baseline over the 6 hours after dosing on the other 3 test days, and peak FEV1 on all test days. Overall, the safety profile of IB/FEN via Respimat® SMI was comparable to that via CFC-MDI.

Conclusion

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

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Notes

  1. The use of tradenames is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This study was sponsored by Boehringer Ingelheim. The sponsor and principal author declare that the study has not been biased as a result of the support so given.

The authors would like to thank their fellow investigators from Belgium, the Netherlands and South Africa for their help with this study:

Belgium: Dr JL Aumann, Dr P Driesen, Dr P Gris, Dr J Machiels, Dr H Slabbynck, Dr I Stappaerts, Dr J Verhaert and Prof. P Vermeire.

The Netherlands: Dr R Aalbers, Dr JPHM Creemers, Dr ME Eland, Dr WBM Evers, Dr SJM Gans, Dr APM Greefhorst, Dr AJ van Harreveld, Dr JLM van Helmond, Dr JHLM van Kasteren, Dr AF Kuipers, Dr J van Noord, Dr HR Pasma, Dr J Prins, Dr R Rammeloo, Dr AJM Schreurs, Dr H Sinnighe Damsté, Dr AP Sips, Dr PI van Spiegel and Dr J Westbroek.

South Africa: Prof. ED Bateman, Dr LG Herbst, Prof. J Joubert, Dr MC Kamdar, Dr U Lalloo, Dr M van der Linden, Dr J Terblanché, and Dr JJ Viljoen.

The authors would also like to acknowledge the help of the following co-investigators: Dr PM van der Berg, Dr EJFM ten Berge, Dr AMG Hendriks, Dr I Roussouw, Dr E Janssens, Dr PB Luursema, Dr H Nell, Dr NJJ Schlösser, Dr FMJ Simons, Dr HH Timmer, Dr MW Verheul, Dr NC van Walree and Dr HJ van der Woude.

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Authors and Affiliations

  1. Respiratory Division, Academic Hospital, University of Brussels, 101 Laarbeeklaan, 1090, Brussels, Belgium

    Walter Vincken

  2. Department of Pneumology, Interconfessioneel Ziekenhuis De Baronie, Breda, The Netherlands

    Theo Bantje

  3. SA Clinical Trials (Pty) Ltd, George, South Africa

    Michelle V. Middle

  4. Boehringer Ingelheim Pharma KG, Ingelheim, Germany

    Fronke Gerken

  5. Boehringer Ingelheim, Brussels, Belgium

    Diane Moonen

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  1. Walter Vincken
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  2. Theo Bantje
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  4. Fronke Gerken
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  5. Diane Moonen
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Correspondence to Walter Vincken.

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Vincken, W., Bantje, T., Middle, M.V. et al. Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via Respimat® Soft Mist™ Inhaler (SMI) versus a Pressurised Metered-Dose Inhaler in Asthma. Clin. Drug Investig. 24, 17–28 (2004). https://doi.org/10.2165/00044011-200424010-00003

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