Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial

Sevim Uzun, RS (Remco) Djamin, JAJW (Jan) Kluytmans, PGH (Paul) Mulder, NE (Nils) Van't Veer, AAM (Anton) Ermens, AJ Pelle, Henk Hoogsteden, Joachim Aerts, Menno van der Eerden

Research output: Contribution to journalArticleAcademicpeer-review

183 Citations (Scopus)

Abstract

Background Macrolide resistance is an increasing problem; there is therefore debate about when to implement maintenance treatment with macrolides in patients with chronic obstructive pulmonary disease (COPD). We aimed to investigate whether patients with COPD who had received treatment for three or more exacerbations in the previous year would have a decrease in exacerbation rate when maintenance treatment with azithromycin was added to standard care. Methods We did a randomised, double-blind, placebo-controlled, single-centre trial in the Netherlands between May 19, 2010, and June 18, 2013. Patients (>= 18 years) with a diagnosis of COPD who had received treatment for three or more exacerbations in the previous year were randomly assigned, via a computer-generated randomisation sequence with permuted block sizes of ten, to receive 500 mg azithromycin or placebo three times a week for 12 months. Randomisation was stratified by use of long-term, low-dose prednisolone (<= 10 mg daily). Patients and investigators were masked to group allocation. The primary endpoint was rate of exacerbations of COPD in the year of treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00985244. Findings We randomly assigned 92 patients to the azithromycin group (n=47) or the placebo group (n=45), of whom 41 (87%) versus 36 (80%) completed the study. We recorded 84 exacerbations in patients in the azithromycin group compared with 129 in those in the placebo group. The unadjusted exacerbation rate per patient per year was 1.94 (95% CI 1.50-2.52) for the azithromycin group and 3.22 (2.62-3.97) for the placebo group. After adjustment, azithromycin resulted in a significant reduction in the exacerbation rate versus placebo (0.58, 95% CI 0.42-0.79; p=0.001). Three (6%) patients in the azithromycin group reported serious adverse events compared with five (11%) in the placebo group. During follow-up, the most common adverse event was diarrhoea in the azithromycin group (nine [19%] patients vs one [2%] in the placebo group; p=0.015). Interpretation Maintenance treatment with azithromycin significantly decreased the exacerbation rate compared with placebo and should therefore be considered for use in patients with COPD who have the frequent exacerbator phenotype and are refractory to standard care.
Original languageUndefined/Unknown
Pages (from-to)361-368
Number of pages8
JournalThe Lancet Respiratory Medicine
Volume2
Issue number5
DOIs
Publication statusPublished - 2014

Cite this