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Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Sanjay Sethi1*, Paul W Jones2, Marlize Schmitt Theron3, Marc Miravitlles4, Ethan Rubinstein5, Jadwiga A Wedzicha6, Robert Wilson7 and the PULSE Study group

Author Affiliations

1 Division of Pulmonary, Critical Care and Sleep Medicine, University of Buffalo, State University of New York, Buffalo, NY, USA

2 Division of Cardiac and Vascular Services, St George's, University of London, UK

3 Clinical Operations, Bayer Pty Ltd, Isando, Johannesburg, South Africa

4 Fundació Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

5 Section of Infectious Diseases, University of Manitoba Faculty of Medicine, Winnipeg, MB, Canada

6 Academic Unit of Respiratory Medicine, The Royal Free and University College Medical School, London, UK

7 Respiratory Medicine, Royal Brompton Hospital, London, UK

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Respiratory Research 2010, 11:10  doi:10.1186/1465-9921-11-10

Published: 28 January 2010

Abstract

Background

Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.

Methods

Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.

Results

At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).

There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).

Conclusions

Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.

Trial registration

ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).