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

Abstract

BackgroundAcute 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.MethodsStable 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.ResultsAt 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%).ConclusionsIntermittent 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 registrationClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).

Chronic Obstructive Pulmonary Disease: Official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care

“…Antibiotic therapy (ABT) may have a positive effect during stable disease in selected phenotypes: in patients with an increased production of phlegm -bronchitic phenotype; in patients with frequent exacerbations; and also in the COPD with bronchiectasis. Some positive effects were observed, particularly with macrolides, most prominently azithromycin, but also with the respiratory fluoroquinolone moxifloxacin 3,[95][96][97][98][99][100][101][102][103] . Long-term application of muco-active agents (erdosteine, carbocysteine, N-acetylcysteine) may be considered for symptomatic persons with the bronchitic phenotype and COPD patients with bronchiectasis 3,104,105 .…”

Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

“…Изучены эффекты интермитти рующих повторных курсов моксифлоксацина на снижение частоты обострений ХОБЛ [133]. Пациен ты с ХОБЛ в течение 5 дней получали либо мокси флоксацин 400 мг в сутки per os, либо плацебо, всего 6 курсов с интервалом в 8 нед.…”

“…Пациен ты с ХОБЛ в течение 5 дней получали либо мокси флоксацин 400 мг в сутки per os, либо плацебо, всего 6 курсов с интервалом в 8 нед. [133].…”

Acute exacerbation in COPD and asthma

“…Mart 2013 yılında FDA azitromisinin kalbin elektrik aktivitesini bozduğunu ve ölümcül ritm kusurlarına sebep olabileceğini belirten bir güvenlik duyurusu yayınladı (135). Bir solunum kinolonu olan moksifloksasinin 400 mg/gün, beş gün, sekiz haftada bir, bir yılda altı kez uygulamasının da KOAH ataklarında %25 azalma yaptığı, özellikle pürülen-mukopürülan balgamı olan hastalarda %45 atak azalmasına sebep olduğu doğrulanmıştır (136).…”