Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial

Introduction: 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 6-17 years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400 mg every 12 h or matching placebo for 8 weeks, followed by an 8 week washout and an 8 week 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 12 years 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) (C) 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.