Chest
Original ResearchBronchiectasisPhase 3 Randomized Study of the Efficacy and Safety of Inhaled Dry Powder Mannitol for the Symptomatic Treatment of Non-Cystic Fibrosis Bronchiectasis
Section snippets
Subjects
Table 1 lists the inclusion and exclusion criteria for study patients recruited from 22 sites, approved by the relevant ethics committees in Australia, New Zealand, and the United Kingdom (e-Appendix 1).
Treatment and Materials
Dry powder mannitol (Bronchitol; Pharmaxis) was supplied in 40-mg capsules. Placebo capsules (10 mg) (Roquette) consisted of nonrespirable (approximately 70 μm) United States Pharmacopeia/British Pharmacopoeia good manufacturing practice crystalline mannitol.
Mannitol and placebo were
Patient Disposition and Baseline Demographics
Patient disposition, ITT, and OLE safety populations are described in Figure 1. There were no statistically significant differences in patient demographics, baseline spirometry, or airway function between the groups (Table 3, e-Table 1). Similar numbers of patients in each group (46.4% mannitol; 43.7% placebo) were having regular physiotherapy to clear their secretions.
Sputum Weight
The change from baseline in the 24-h sputum weight after 12 weeks of treatment was significantly different between the mannitol
Discussion
Although bronchiectasis is a major contributor to chronic respiratory morbidity and mortality,2, 6 clinically relevant end points have not been established firmly with regulatory authorities. Consequently, a number of established and exploratory assessments were included in our study, to examine the efficacy of mannitol. However, because the problems in bronchiectasis arise from poor clearance of mucus and consequently poor health, and mannitol is known to facilitate mucus clearance,18 our
Conclusion
Mannitol inhaled bid for 12 weeks in patients with mild-to-moderate bronchiectasis led to a significant difference in expectorated sputum. In a substudy of patients having CT scans, there was a reduction in mucus plugging. Despite improvements in quality of life from baseline, these failed to reach statistical significance compared with placebo. Mannitol therapy was safe and well tolerated for over 3 to 12 months. A large 12-month study is underway to further investigate the effect of mannitol
Acknowledgments
Author contributions: Dr Charlton is the guarantor of the paper and takes responsibility for the integrity of the work as a whole, from inception to published article.
Dr Bilton: contributed to the interpretation of the data, writing of the manuscript, approval of the final version, and final submission of the manuscript for publication.
Dr Daviskas: contributed to the interpretation of the data, writing of the manuscript, and approval of the final version.
Dr Anderson: contributed to the
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Funding/Support: This study was funded by Pharmaxis Ltd.
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