Eur Respir J. 2011 Apr 8. [Epub ahead of print]
Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.
* Royal Brompton Hospital London United Kingdom.
This international phase III study of inhaled dry powder mannitol was a randomised double blind 26 week study, followed by a further 26 week open-label extension. 324 subjects were randomised 3:2 to mannitol (400 mg bid) or control. The primary efficacy endpoint was to determine the change in FEV1 over the double-blind phase. Secondary endpoints included changes in FVC and pulmonary exacerbations.
A significant improvement in FEV1 was seen over 26 weeks (p<0.001) and was apparent by 6 weeks irrespective of concomitant rhDNase use. At 26 weeks, there was a significant improvement of 92.9 mL in FEV1 for subjects receiving mannitol compared with control (change from baseline 118.9 mL [6.5%] vs. 26.0 mL [2.4%]; p<0.001). Improvements in FEV1 were maintained up to 52 weeks in the open-label part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045).
The incidence of adverse events (AE) was similar in both groups, though treatment related AEs were higher in the mannitol compared to the control group. The most common mannitol related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol shows sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.