Treatment failure may be significantly reduced by a 3-month course of azithromycin for acute chronic obstructive pulmonary disease (COPD) exacerbations that require hospitalization, according to a study published in the American Journal of Respiratory and Critical Care Medicine. Clinical benefits appear to be sustained only with prolonged treatment.
The double-blind, placebo-controlled, multi-center BACE (Belgian Trial With Azithromycin for Acute COPD; ClinicalTrials.gov Identifier: NCT02135354) study included 301 individuals hospitalized for acute exacerbations in COPD. All participants had ≥1 exacerbation in the prior year treated with systemic corticosteroids and/or antibiotics, were ≥18 years old, and had a smoking history of ≥10 pack-years. Participants were randomly assigned 1:1 to either azithromycin 500 mg daily (3 day loading dose) or placebo within 2 days of admission. The intervention drug accompanied standard treatment with antibiotics and systemic corticosteroids, then was continued for 3 months at 250 mg every 2 days. Follow-up lasted for 6 months after the initial 3 month period.
The primary end point was time-to-first-event analysis to evaluate the 3-month treatment failure rate. Treatment failure was defined as a combination of step-up in hospital care or readmission for respiratory reasons, treatment intensification with medication, or all-cause mortality. A log-rank test with proportional hazards was used for survival analysis, while a Kaplan-Meier survival analysis was used to examine mortality and treatment failure, which were compared with a log-rank test between groups. Safety outcomes included assessing serious adverse events, the Speech, Spatial, and Qualities of Hearing Scale – 5 items questionnaire; and macrolide-resistant pathogens in sputum samples.
Among the study population, 147 were assigned to azithromycin and 154 to placebo. Treatment failure within 3 months in participants who received azithromycin was 49% and in those who received placebo was 60%, yielding a hazard ratio of 0.73 (95% CI, 0.53-1.01; P =.0526). Treatment intensification with medication occurred in 47% of the intervention group compared with 60% of the placebo group (P =.0272), all-cause mortality in 2% of the intervention group vs 4% of the placebo group (P =.5075), and step-up in hospital care or readmission for respiratory reasons in 13% of the intervention group compared with 28% of the placebo group (P =.0024). After 6 months of withdrawal, clinical benefits disappeared.
Limitations to this study included failure to meet target enrollment, limited generalizability and external validity, the inclusion of acute COPD exacerbations of bacterial and viral etiology, potential inhomogeneity between sites, a lack of audiometry, and a low rate of sputum samples.
“A careful and individualized approach to the selection of patients, with regards to pro‐arrhythmic effects and the development of antibiotic resistance, would be recommended,” the researchers concluded.
Disclosures: Several authors report financial associations with pharmaceutical companies. For a full list of disclosures, please visit the reference.
Vermeersch K, Gabrovska M, Aumann J, et al; on behalf of the BACE trial investigators. Azithromycin during acute COPD exacerbations requiring hospitalization (BACE): a multicentre, randomized, double-blind, placebo-controlled trial [published online May 3, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201901-0094OC