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

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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/mu L, 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.
Keywords
Recurrent event, Readmission, Macrolide, CRP, Eosinophil count, OBSTRUCTIVE PULMONARY-DISEASE, THERAPY

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MLA
Vermeersch, Kristina, et al. “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, vol. 20, no. 1, 2019.
APA
Vermeersch, K., Belmans, A., Bogaerts, K., Gyselinck, I., Cardinaels, N., Gabrovska, M., … Janssens, W. (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).
Chicago author-date
Vermeersch, Kristina, Ann Belmans, Kris Bogaerts, Iwein Gyselinck, Nina Cardinaels, Maria Gabrovska, Joseph Aumann, et al. 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).
Chicago author-date (all authors)
Vermeersch, Kristina, 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 Brusselle, and Wim Janssens. 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).
Vancouver
1.
Vermeersch K, Belmans A, Bogaerts K, Gyselinck I, Cardinaels N, Gabrovska M, et al. 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. 2019;20(1).
IEEE
[1]
K. Vermeersch et al., “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, vol. 20, no. 1, 2019.
@article{8645810,
  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/mu L, 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.}},
  articleno    = {{237}},
  author       = {{Vermeersch, Kristina and Belmans, Ann and Bogaerts, Kris and Gyselinck, Iwein and Cardinaels, Nina and Gabrovska, Maria and Aumann, Joseph and Demedts, Ingel K. and Corhay, Jean-Louis and Marchand, Eric and Slabbynck, Hans and Haenebalcke, Christel and Vermeersch, Stefanie and Verleden, Geert M. and Troosters, Thierry and Ninane, Vincent and Brusselle, Guy and Janssens, Wim}},
  issn         = {{1465-993X}},
  journal      = {{RESPIRATORY RESEARCH}},
  keywords     = {{Recurrent event,Readmission,Macrolide,CRP,Eosinophil count,OBSTRUCTIVE PULMONARY-DISEASE,THERAPY}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{12}},
  title        = {{Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - a post-hoc analysis of the BACE randomized controlled trial}},
  url          = {{http://dx.doi.org/10.1186/s12931-019-1208-6}},
  volume       = {{20}},
  year         = {{2019}},
}

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