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.

TRIAL REGISTRATION:

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

• Authors: Sanjay Sethi, Paul W Jones, Marlize Schmitt Theron, Marc Miravitlles, Ethan Rubinstein, Jadwiga A Wedzicha, Robert Wilson, PULSE Study group
• Journal: Respiratory research (Respir Res) Vol. 11 Pg. 10 (Jan 28 2010) ISSN: 1465-993X [Electronic] England
• PMID: 20109213 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Aza Compounds
• Fluoroquinolones
• Quinolines
• Moxifloxacin

Topics

• Aged
• Aged, 80 and over
• Anti-Infective Agents (administration & dosage)
• Aza Compounds (administration & dosage)
• Chronic Disease
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Fluoroquinolones
• Humans
• Male
• Middle Aged
• Moxifloxacin
• Placebo Effect
• Pulmonary Disease, Chronic Obstructive (diagnosis, drug therapy)
• Quinolines (administration & dosage)
• Secondary Prevention
• Treatment Outcome