title: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, University of Buffalo, State University of New York, Buffalo, NY, USA. ssethi@buffalo.edu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.forename: Marlize Schmitt
authors.initials: MS
authors.lastname: Theron
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
authors.forename: Ethan
authors.initials: E
authors.lastname: Rubinstein
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage; D001372:Aza Compounds / Q000008:administration & dosage*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D011804:Quinolines / Q000008:administration & dosage*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin