title: Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study.
abstract: OBJECTIVE
  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.
  
  
  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 -0.98% (95% CI -2.74% to 0.86%) in the intention-to-treat population (n=373) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics, University of Düsseldorf, Düsseldorf, Germany. schuster@med.uni-duesseldorf.de
authors.forename: Antje
authors.initials: A
authors.lastname: Schuster
authors.forename: Cynthia
authors.initials: C
authors.lastname: Haliburn
authors.forename: Gerd
authors.initials: G
authors.lastname: Döring
authors.forename: Martin Harris
authors.initials: MH
authors.lastname: Goldman
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents; D017326:Clinical Trials, Phase III as Topic; D003091:Colistin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011208:Powders; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000150:complications; D011550:Pseudomonas aeruginosa; D014031:Tobramycin / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; C004691:colistinmethanesulfonic acid; D014031:Tobramycin; D003091:Colistin