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Original Research: Bronchiectasis |

Phase 3 Randomized Study of the Efficacy and Safety of Inhaled Dry Powder Mannitol for the Symptomatic Treatment of Non-Cystic Fibrosis BronchiectasisMannitol for Non-Cystic Fibrosis Bronchiectasis

Diana Bilton, MD; Evangelia Daviskas, MBiomedE, PhD; Sandra D. Anderson, PhD, DSc; John Kolbe, MBBS; Gregory King, MBChB, PhD; Rob G. Stirling, MBBCh(Hons); Bruce R. Thompson, PhD; David Milne, MBChB; Brett Charlton, PhD; for the B301 Investigators
Author and Funding Information

From the Department of Respiratory Medicine (Dr Bilton), Royal Brompton Hospital, London, England; the Department of Respiratory and Sleep Medicine (Drs Daviskas and Anderson), Royal Prince Alfred Hospital, Sydney, NSW, Australia; the Department of Respiratory Medicine (Dr King), The Royal North Shore Hospital, Sydney, NSW, Australia; the Medical Department (Dr Charlton), Pharmaxis, Sydney, NSW, Australia; the Department of Allergy Immunology and Respiratory Medicine (Dr Stirling and Prof Thompson), The Alfred Hospital, Melbourne, VIC, Australia; the Department of Medicine (Dr Kolbe), University of Auckland, Auckland, New Zealand; and the Department of Radiology (Dr Milne), Auckland District Health Board, Auckland, New Zealand.

Correspondence to: Diana Bilton, MD, Department of Respiratory Medicine, Royal Brompton Hospital, Sydney St, London, SW3 6NP, England; e-mail: D.Bilton@rbht.nhs.uk


Funding/Support: This study was funded by Pharmaxis Ltd.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):215-225. doi:10.1378/chest.12-1763
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Background:  Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis. This study’s objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks.

Methods:  Patients with bronchiectasis confirmed by high-resolution CT (HRCT) scan, aged 15 to 80 years, with FEV1 ≥ 50% predicted and ≥ 1 L participated in a randomized, placebo-controlled, double-blind study. Patients with a negative mannitol provocation test were randomized to inhale 320 mg mannitol (n = 231) or placebo (n = 112) bid for 12 weeks. To further assess safety, the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks. Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George’s Respiratory Questionnaire (SGRQ) score.

Results:  There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks (95% CI, 1.64-7.00; P = .002) between mannitol and placebo; however, this was largely driven by a decrease in sputum weight in the placebo group. This was associated, in turn, with more antibiotic use in the placebo group (50 of 112 [45%]) than in the inhaled mannitol group (85 of 231 [37%]). There was no statistical difference between the groups (P = .304) in total SGRQ score (mannitol, −3.4 points [95% CI, −4.81 to −1.94] vs placebo, −2.1 points [95% CI, −4.12 to −0.09]). In a subgroup study (n = 82), patients receiving mannitol showed less small airway mucus plugging on HRCT scan at 12 weeks compared with patients receiving placebo (P = .048). Compliance rates were high, and mannitol was well tolerated with adverse events similar to those of placebo.

Conclusion:  Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group, a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use.

Trial registry:  ClinicalTrials.gov; No.: NCT0027753; URL: www.clinicaltrials.gov

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