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

Kristina Vermeersch, Ann Belmans, Kris Bogaerts, Iwein Gyselinck, Nina Cardinaels, Maria Gabrovska, Joseph Aumann, Ingel K. Demedts, Jean Louis Corhay, Eric Marchand, Hans Slabbynck, Christel Haenebalcke, Stefanie Vermeersch, Geert M. Verleden, Thierry Troosters, Vincent Ninane, Guy G. Brusselle, Wim Janssens, Vincent Ninane, Joseph AumannIngel K. Demedts, Hans Slabbynck, Christel Haenebalcke, Rudi Peché, Guy G. Brusselle, Walter Vincken, Jean Louis Corhay, Michiel Haerens, Antoine Fremault, Tine Lauwerier, Alix Debrock, Jan Lamont, Geert Tits, Paul Jordens, Alain Delobbe, Jean Benoît Martinot

Research output: Contribution to journalArticle

Abstract

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 .

Original languageEnglish
Article number237
Pages (from-to)237
JournalRespiratory Research
Volume20
Issue number1
DOIs
Publication statusPublished - 29 Oct 2019

Keywords

  • CRP
  • Eosinophil count
  • Macrolide
  • Readmission
  • Recurrent event

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    Vermeersch, K., Belmans, A., Bogaerts, K., Gyselinck, I., Cardinaels, N., Gabrovska, M., Aumann, J., Demedts, I. K., Corhay, J. L., Marchand, E., Slabbynck, H., Haenebalcke, C., Vermeersch, S., Verleden, G. M., Troosters, T., Ninane, V., Brusselle, G. G., Janssens, W., Ninane, V., ... Martinot, J. B. (2019). Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - A post-hoc analysis of the BACE randomized controlled trial. Respiratory Research, 20(1), 237. [237]. https://doi.org/10.1186/s12931-019-1208-6