Study design (if review, criteria of inclusion for studies)
This was a randomised, open-label, crossover, dose response study.
Participants
48 CF patients with a mean (SD) FEV(1) % predicted of 64 (13.2)
Interventions
Following a 2-week treatment with mannitol 400mg b.i.d., patients received a further 3 treatments with 40mg, 120mg or 240mg b.i.d. for 2weeks each, in random order.
Outcome measures
FEV(1) and FVC.
Main results
The study demonstrated a dose dependent increase in FEV(1) and FVC. The 400mg dose showed the greatest improvement and the 40mg 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 40mg, 120mg, 240mg and 400mg treatments. There was a statistically significant change in FEV(1) for 400mg compared to 40mg (p<0.0001) but the difference with 120mg and 240mg did not reach significance. The mean % change in FVC was -0.90, 1.74, 3.07 and 8.14, for the 40mg, 120mg, 240mg and 400mg treatment arms, with p=0.0001, p=0.0037 and p=0.0304 respectively when compared to 400mg. The highest tested dose of 400mg had a similar safety profile to the other doses tested. The change in FEV(1) and FVC by dose in the paediatric age group (<18years) was similar to the results in the adult population.
Authors' conclusions
Based on these results the 400mg b.i.d. dose has been further studied in phase III trials.