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Thorax doi:10.1136/thoraxjnl-2012-202059
  • Cystic fibrosis
  • Original article

Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study

Open Access
  1. for the Freedom Study Group
  1. 1Department of Paediatrics, University of Düsseldorf, Düsseldorf, Germany
  2. 2Hartington Data Management and Statistics, London, UK
  3. 3Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany
  4. 4Forest Laboratories, Dartford, UK
  1. Correspondence to Dr Antje Schuster, Zentrum für Kinder und Jugendmedizin, Moorenstrasse 5, Düsseldorf 40225, Germany; schuster{at}med.uni-duesseldorf.de
  • Received 17 April 2012
  • Accepted 11 October 2012
  • Published Online First 7 November 2012

Abstract

Purpose To assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis (CF) aged ≥6 years with chronic Pseudomonas aeruginosa lung infection.

Study design and methods A prospective, centrally randomised, phase III, open-label study in patients with stable CF aged ≥6 years with chronic P aeruginosa lung infection. Patients were randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24 weeks.

Results 380 patients were randomised. After logarithmic transformation of data due to a non-normal distribution, adjusted mean difference between treatment groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV1% predicted) at week 24 was −0.97% (95% CI −2.74% to 0.86%) in the intention-to-treat population (n=374) and −0.56% (95% CI −2.71% to 1.70%) in the per protocol population (n=261). The proportion of colistin-resistant isolates in both groups was ≤1.1%. The number of adverse events was similar in both groups. Significantly more patients receiving CDPI rated their device as ‘very easy or easy to use’ (90.7% vs 53.9% respectively; p<0.001).

Conclusion CDPI demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment. There was no emergence of resistance of P aeruginosa to colistin. Overall, CDPI was well tolerated.

Trial Reg No EudraCT 2004-003675-36.

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