Journal Article

Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo – a post-hoc analysis of the BACE randomized controlled trial

Vermeersch, Kristina, Gabrovska, Maria, Cardinaels, Nina, Brusselle, Guy G., Aumann, Joseph, Demedts, Ingel K., Corhay, Jean-Louis, Vermeersch, Stefanie, Haenebalcke, Christel, Belmans, Ann, Slabbynck, Hans, Janssens, Wim, Marchand, Eric, Troosters, Thierry, Bogaerts, Kris, Gyselinck, Iwein, Verleden, Geert M., Ninane, Vincent

2019

Overview

Background In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. Objectives (1) To investigate the intervention’s effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions. Methods Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time. Results Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p  = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p  = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p  = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p  = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p  = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. Conclusions This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy. Trial registration ClinicalTrials.gov number. NCT02135354 .

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aged / Anti-Bacterial Agents - therapeutic use / Azithromycin / Azithromycin - therapeutic use / Biological markers / Cardiovascular & respiratory systems / Care and treatment / Chronic obstructive lung disease / Clinical trials / CRP / Development and progression / Disease Progression / Double-Blind Method / Eosinophil count / Female / Forecasts and trends / Hospital admission and discharge / Human health sciences / Humans / Macrolide / Male / Medicine / Medicine & Public Health / Middle Aged / Mortality / Patient outcomes / Patient Readmission - trends / Pneumology/Respiratory System / Pulmonary Disease, Chronic Obstructive - diagnosis / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - epidemiology / Readmission / Recurrent event / Sciences de la santé humaine / Severity of Illness Index / Systèmes cardiovasculaire & respiratoire / Treatment Failure