title: Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial.
abstract: BACKGROUND
  Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF).
  
  
  METHODS
  The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1).
  
  
  RESULTS
  A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group.
  
  
  CONCLUSIONS
  In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531).
authors.affiliation: KUL Leuven, Leuven, Belgium. Electronic address: christiane.deboeck@uz.kuleuven.ac.be.
authors.forename: K
authors.initials: K
authors.lastname: De Boeck
authors.affiliation: VU University Medical Center, Amsterdam, Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Haarman
authors.affiliation: Paediatric Respiratory Medicine, Oxford Children's Hospital, Oxford, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Hull
authors.affiliation: McGill University, Montreal, QC, Canada.
authors.forename: L C
authors.initials: LC
authors.lastname: Lands
authors.affiliation: University Children's Hospital, Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Moeller
authors.affiliation: Hôpital Robert Debré, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Munck
authors.affiliation: University Children's Hospital, Tuebingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Riethmüller
authors.affiliation: Erasmus Medical Centre, Rotterdam, Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Tiddens
authors.affiliation: Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Volpi
authors.affiliation: Pharmaxis Ltd, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Leadbetter
authors.affiliation: Pharmaxis Ltd, Sydney, NSW, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Charlton
authors.affiliation: UZ Brussel, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Malfroot
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects; D009079:Mucociliary Clearance / Q000187:drug effects*; D011788:Quality of Life; D013183:Sputum / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D004234:Diuretics, Osmotic; D008353:Mannitol
keywords: Cystic fibrosis; FEV1; Mannitol; Paediatric; Randomised