title: Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study.
abstract: BACKGROUND
  New treatment strategies are needed to improve airway clearance and reduce the morbidity and the time burden associated with cystic fibrosis (CF).
  
  
  OBJECTIVE
  To determine whether long-term treatment with inhaled mannitol, an osmotic agent, improves lung function and morbidity.
  
  
  METHODS
  Double-blind, randomized, controlled trial of inhaled mannitol, 400 mg twice a day (n = 192, "treated" group) or 50 mg twice a day (n = 126, "control" group) for 26 weeks, followed by 26 weeks of open-label treatment.
  
  
  RESULTS
  The primary endpoint was absolute change in FEV(1) from baseline in treated versus control groups, averaged over the study period. Secondary endpoints included other spirometric measurements, pulmonary exacerbations, and hospitalization. Clinical, microbiologic, and laboratory safety were assessed. The treated group had a mean improvement in FEV(1) of 105 ml (8.2% above baseline). The treated group had a relative improvement in FEV(1) of 3.75% (P = 0.029) versus the control group. Adverse events and sputum microbiology were similar in both treatment groups. Exacerbation rates were low, but there were fewer in the treated group (hazard ratio, 0.74; 95% confidence interval, 0.42-1.32; P = 0.31), although this was not statistically significant. In the 26-week open-label extension study, FEV(1) was maintained in the original treated group, and improved in the original control group to the same degree.
  
  
  CONCLUSIONS
  Inhaled mannitol, 400 mg twice a day, resulted in improved lung function over 26 weeks, which was sustained after an additional 26 weeks of treatment. The safety profile was also acceptable, demonstrating the potential role for this chronic therapy for CF. Clinical trial registered with www.clinicaltrials.gov (NCT 00630812).
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195-6522, USA. moira@u.washington.edu
authors.forename: Moira L
authors.initials: ML
authors.lastname: Aitken
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bellon
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Flume
authors.forename: Howard G
authors.initials: HG
authors.lastname: Fox
authors.forename: David E
authors.initials: DE
authors.lastname: Geller
authors.forename: Eric G
authors.initials: EG
authors.lastname: Haarman
authors.forename: Helge U
authors.initials: HU
authors.lastname: Hebestreit
authors.forename: Allen
authors.initials: A
authors.lastname: Lapey
authors.forename: I Manjula
authors.initials: IM
authors.lastname: Schou
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Zuckerman
authors.forename: Brett
authors.initials: B
authors.lastname: Charlton
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004234:Diuretics, Osmotic / Q000008:administration & dosage; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D011208:Powders; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004234:Diuretics, Osmotic; D011208:Powders; D008353:Mannitol