Diana Bilton1, Gregory Tino2, Alan F Barker3, Daniel C Chambers4, Anthony De Soyza5, Lieven J A Dupont6, Conor O'Dochartaigh7, Eric H J van Haren8, Luis Otero Vidal9, Tobias Welte10, Howard G Fox11, Jian Wu11, Brett Charlton11. 1. Department of Respiratory Medicine, Royal Brompton Hospital, London, UK. 2. Department of Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Medical Centre, Philadelphia, Pennsylvania, USA. 3. Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA. 4. Queensland Lung Transplant Service, The Prince Charles Hospital, Chermside, Queensland, Australia School of Medicine, The University of Queensland, Herston, Queensland, Australia. 5. Institute of Cellular Medicine Newcastle University & Sir William Leech Centre, Freeman Hospital, Newcastle-upon-Tyne, UK. 6. UZL University Hospital Leuven, Leuven, Belgium. 7. Department of Respiratory Medicine, Middlemore Hospital, Auckland, New Zealand. 8. Atrium MC Pulmonology Department, Heerlen, The Netherlands. 9. Hospital Interzonal Especializado en Agudos y Cronicos "Dr Antonio A. Cetrangolo", Partido de Vicente Lopez Provincia de Buenos Aires, Buenos Aires, Argentina. 10. Medizinische Hochschule Hannover, Klinik fur Pneumologie, Hannover, Germany. 11. Pharmaxis Ltd, Frenchs Forest, Sydney, NSW, Australia.
Abstract
RATIONALE: Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. OBJECTIVES: To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). METHODS:Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. MAIN RESULTS:461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. CONCLUSIONS:Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. TRIAL REGISTRATION NUMBER: NCT00669331. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
RCT Entities:
RATIONALE: Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. OBJECTIVES: To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). METHODS:Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. MAIN RESULTS: 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. CONCLUSIONS:Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. TRIAL REGISTRATION NUMBER: NCT00669331. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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