Inhaled mannitol in patients with cystic fibrosis: A randomised open-label dose response trial

Abstract

Background Cystic fibrosis (CF) is characterised by impaired mucociliary clearance (MCC), chronic inflammation and infection, and progressively deteriorating lung function. Inhaled mannitol (Bronchitol) has been shown to increase MCC and cough clearance and FEV 1 in CF patients, contributing to better lung hygiene and consequently a slower decline in lung function. This study was designed to determine the dose relationship of mannitol treatment and improvement in FEV 1 and FVC as well as safety. Methods This was a randomised, open-label, crossover, dose response study. Following a 2-week treatment with mannitol 400 mg b.i.d., 48 CF patients with a mean (SD) FEV 1 % predicted of 64 (13.2), received a further 3 treatments with 40 mg, 120 mg or 240 mg b.i.d. for 2 weeks each, in random order. Results The study demonstrated a dose dependent increase in FEV 1 and FVC. The 400 mg dose showed the greatest improvement and the 40 mg dose had no discernible effect. The mean percent change in FEV 1 was −1.57%, 3.61%, 3.87% and 8.75% respectively for the 40 mg, 120 mg, 240 mg and 400 mg treatments. There was a statistically significant change in FEV 1 for 400 mg compared to 40 mg (p < 0.0001) but the difference with 120 mg and 240 mg did not reach significance. The mean % change in FVC was −0.90, 1.74, 3.07 and 8.14, for the 40 mg, 120 mg, 240 mg and 400 mg treatment arms, with p = 0.0001, p = 0.0037 and p = 0.0304 respectively when compared to 400 mg. The highest tested dose of 400 mg had a similar safety profile to the other doses tested. The change in FEV 1 and FVC by dose in the paediatric age group (< 18 years) was similar to the results in the adult population. Conclusion Based on these results the 400 mg b.i.d. dose has been further studied in phase III trials.