Clinical studies

Kaessner F, Hodder R, Bateman ED. A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat® Soft Mist™ Inhaler in patients with asthma and chronic obstructive pulmonary disease. Drugs 2004; 64:167-182

This is a review of 5 clinical studies investigating dosages of Ipratropium bromide/ Fenoterol (IB/Fen) via Respimat® SMI in single and multi dose administration regimes. Four studies are conducted in patients with asthma and 1 study in COPD patients. The results of the trials demonstrate that IB/Fen via Respimat® SMI allows a reduction in the nominal dose while offering similar therapeutic efficacy and safety to the CFC-MDI formulation.

Von Berg A et al. 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. Ped Pulmonology 2004; 37: 264-272.

In a multi-centre, randomised, double-blind parallel-group study in paediatric patients (6-15 yrs), it was shown that ipratropium bromide/fenoterol was at least as effective and well tolerated when delivered via Respimat® SMI as when delivered via an MDI plus spacer. Respimat® SMI also allowed a reduction in the nominal dose.

Vincken W et al. Long-Term Efficacy and Safety of Ipratropium Bromide plus Fenoterol via Respimat® Soft Mist™ Inhaler in Asthma. Clin Drug Invest 2004; 24(1): 17-28

In a multi-centre, randomised, double-blind, placebo-controlled parallel-group study in 631 adult patients with stable asthma, fenoterol/ipratropium bromide delivered by Respimat® SMI at doses of 10/25 and 20/50 was therapeutically equivalent to doses of 40/100 delivered by pMDI. Safety profiles were comparable.

Kilfeather SA et al. Improved delivery of ipratropium bromide/fenoterol from Respimat® Soft Mist™ Inhaler in patients with COPD. Respir Med 2004; 98: 387-397.

In a twelve week, multi-centre, randomised, double-blind, parallel-group study, Ipratropium bromide/Fenoterol 20/50 delivered from Respimat® SMI was equivalent to ipratropium bromide/fenoterol 40/100 delivered from a pMDI. The safety profiles were comparable.

Goldberg J et al. Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler. Eur Respir J 2001; 17:Issue 2: 225-232.

In a five-period, cross-over design, the safety and efficacy of delivering Fenoterol/Ipratropium bromide via Respimat® SMI and the pMDI were compared.

Van Noord JA et al. Delivery of Fenoterol via Respimat®, a novel 'Soft Mist' Inhaler. Respiration 2000; 67: 672-678.

This study confirms that effective, well tolerated bronchodilatation can be achieved via Respimat® SMI at a much lower dose compared to an MDI. The test drug used was fenoterol.

Paula Anderson. Comprehensive review on "Use of Respimat® Soft Mist™ Inhaler in COPD patients" Int J of COPD 2006; 1(3) 251-259

In this comprehensive review key aspects of the cloud properties of the new generation inhaler Respimat® SMI are discussed as well as patient centred outcomes such as correct inhaler use, patient satisfaction and accacptability.

Rau JL. The inhalation of drugs: advantages and problems. Respir Care2005; 50: 367-82

This review summarises the full range of inhalation devices of the past, present and some potential future inhaler devices. It also looks into potential improvements in aerosol delivery including better standardization of function and use, greater reliability and reduction of drug loss.

Dalby K, Spallek M, Voshaar T. A review of the development of Respimat® Soft Mist™Inhaler. Int J. Pharm 2004; 283: 1-9.

This review article gives an overview of the concept, mode of action and the resulting clinical performance of the new generation inhaler Respimat® Soft Mist™ Inhaler (SMI). The aerosol cloud of Respimat® SMI is much slower and the cloud duration much longer compared to pMDIs and DPIs. It also contains a higher fine particle fraction. The combination of these features improves the delivered dose to the lungs. Due to the higher dose delivered to the lungs it was expected to achieve the same efficacy of drugs for a smaller nominal dose in the Respimat® SMI compared to pMDIs. This was confirmed for the combination product ipratropium bromide/ fenoterol (Berodual).

Denyer J, et al. New liquid drug aerosol devices for inhalation therapy. Eur Respir Rev 2000; 10: 187-191.

The development of new liquid drug aerosol delivery systems, including Respimat® SMI, is discussed, along with the need for the European Respiratory Society (ERS) to redefine the term nebuliser. The current definition is a device to generate an aerosol from an aqueous drug, which is supplied separately. Respimat® Soft Mist™ Inhaler does this, but is closer to an MDI. The ERS needs to expand the definition of a nebuliser and provide clear information about the differences between devices.

Ganderton D. Targeted delivery of inhaled drugs: current challenges and future goals. J Aerosol Med 1999; 12 (Suppl 1): S3-S8.

A brief review of the advantages and disadvantages of MDIs, DPIs and nebulisers, highlighting the continuing need to effectively target drugs to the lungs. The characteristics of the 'ideal' inhaler device required to achieve this are discussed, along with a brief description of Respimat® Soft Mist™ Inhaler, a propellant-free inhaler in advanced development.

Dolovich M. New propellant-free technologies under investigation. J Aerosol Med 1999; 12 (Suppl 1): S9-S17.

A review of the propellant-free technologies under investigation for the delivery of aerosolized solutions- (adaptive aerosol delivery devices, metered dose liquid inhalers including Respimat® Soft Mist™ Inhaler, and breath-actuated nebulizers) and dry powders (single capsule, bulk reservoir, or multidose devices) to the lung.

Agnew JE. Introduction: Towards better delivery of inhaled medication J Aerosol Med 1999; 12 (Suppl 1): S1-S2.

A short overview of the characteristics associated with current inhalation devices, including their propellants, and the pressure from patients for better ways to manage their respiratory problems. A brief introduction to current research in the area, including the search for alternative energy sources, using Respimat® SMI as
an example.

S.P. Newman et al. An In Vitro Study to Assess Facial and Ocular Deposition from Respimat® Soft Mist™ inhaler J Aerosol Med, Vol 20, Nr 1, 2007, Pp 7-12

This studie investigated facial and eye deposition from Respimat® Soft Mist™ Inhaler in several potential missuse situation ( e.g. potential accidental firing of Respimat® outside the body). Deposition was quantified by gamma camera on a removable face mask that was fitted to a maniquin after firing a radiolabbed aqueous placebo formulation from the Respimat® Soft Mist™ Inhaler in three pre-defined positions outside the head. The eyes were simulated by adhesive plaster patches.Total face deposition averaged between 7.3% abnd 9.1%; eye deposition averaged between 0.1% and 0.6% respectively. It is concluded that there is little potential for unwanted side effects due to the very low deposition figures if Respimat® is accedentally fired outside the body or fired at the same time when the patient exhales.

Patel KR, Pavia D, Lowe L, Spiteri M Inhaled Ethanolic and Aqueous Solutions via Respimat® Soft Mist ™ Inhaler Are Well-Tolerated in Asthma Patients Respiration 2006; 73:434–440

The objective of this randomized, double-blind, three-period, cross-over study was to establish comparable safety of inhaled ethanolic and aqueous placebo solution to saline solution when inhaled from asthmatic patients via Respimat® SMI. The study did show that ehtanolic and aqueous solutions administered via Respimat® SMI are safe with regards to paradoxical bronchoconstriction in asthma patients with airway hyper-reactivity.

Hodder R et al. Low incidence of paradoxical bronchoconstriction in asthma and COPD patients during chronic use of Respimat® soft mist inhaler. Respir Med 2005; 99:1087-95

Bronchodilators administered via Respimat® SMI are preserved and stabilised with low concentrations of benzalkonium chloride and ethylene diamin e tetra acetic acid. These substances have been reported to cause dose-related paradoxical bronchoconstriction. In total , 631 asthma and 1538 COPD patients participated for 12 weeks in three different clinical trials . No occurrences of bronchospasm were reported with Respimat® SMI on any test day.

Hodder R et al. Comparison of the safety relating to paradoxical bronchoconstriction of ipratropium bromide (IB) alone or combined with fenoterol hydrobromide (FEN) inhaled from a new soft mist inhaler (SMI) and from a conventional metered dose inhaler (CFC-MDI) in asthma and COPD patients Eur Respir J 2002; 20 (Suppl 38): P1594

In three phase III studies with Respimat® SMI in a total of 2169 asthma and COPD patients, no paradoxical bronchoconstriction was observed. These studies demonstrate a good safety profile of Respimat® SMI with regard to paradoxical bronchoconstriction.

Kohler D, Pavia D, Dewberry H, Hodder R. Low incidence of paradoxical bronchoconstriction with bronchodilator drugs administered by Respimat® Soft Mist™ inhaler:results from phase II single-dose crossover studies. Respiration ew; 71: 469-476.

This paper compares the incidence of paradocical bronchonconstriction when administering bronchodilator drugs via Respimat® SMI of a CFC-MDI in asthma and COPD patients. Pooled data from 9 phase II studies show a low incidence of adverse events indicative for paradoxical bronchoconstriction in patients using Respimat® SMI and similar in nature to that seen when administering drugs to patients from pMDIs.