Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial

Kristina Vermeersch, Maria Gabrovska, Joseph Aumann, Ingel K. Demedts, Jean Louis Corhay, Eric Marchand, Hans Slabbynck, Christel Haenebalcke, Michiel Haerens, Shane Hanon, Paul Jordens, Rudi Peché, Antoine Fremault, Tine Lauwerier, Anja Delporte, Bert Vandenberk, Rik Willems, Stephanie Everaerts, Ann Belmans, Kris BogaertsGeert M. Verleden, Thierry Troosters, Vincent Ninane, Guy G. Brusselle, Wim Janssens

Research output: Contribution to journalArticle

Abstract

Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of anAECOPDrequiring hospitalization remains to be defined. Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for anAECOPDand had a smoking history of>10 packyears and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated theTF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or allcause mortality. Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P=0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal. Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.

Original languageEnglish
Pages (from-to)857-868
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume200
Issue number7
DOIs
Publication statusPublished - 1 Oct 2019

Keywords

  • Composite
  • Macrolide
  • Readmission
  • Time to event
  • Treatment failure

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    Vermeersch, K., Gabrovska, M., Aumann, J., Demedts, I. K., Corhay, J. L., Marchand, E., Slabbynck, H., Haenebalcke, C., Haerens, M., Hanon, S., Jordens, P., Peché, R., Fremault, A., Lauwerier, T., Delporte, A., Vandenberk, B., Willems, R., Everaerts, S., Belmans, A., ... Janssens, W. (2019). Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization (BACE) a multicenter, randomized, double-blind, placebo-controlled trial. American Journal of Respiratory and Critical Care Medicine, 200(7), 857-868. https://doi.org/10.1164/rccm.201901-0094OC