Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial

Am J Respir Crit Care Med. 2019 Oct 1;200(7):857-868. doi: 10.1164/rccm.201901-0094OC.


Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring 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 an AECOPD and had a smoking history of ≥10 pack-years 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 the TF 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 all-cause 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.

Keywords: composite; macrolide; readmission; time to event; treatment failure.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / therapeutic use
  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / therapeutic use*
  • Clindamycin / therapeutic use
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids / therapeutic use
  • Hospitalization
  • Humans
  • Macrolides / therapeutic use
  • Male
  • Middle Aged
  • Mortality
  • Muscarinic Antagonists / therapeutic use
  • Patient Readmission
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones / therapeutic use
  • Treatment Failure*
  • Vital Capacity
  • beta-Lactams / therapeutic use


  • Adrenergic beta-Agonists
  • Anti-Bacterial Agents
  • Glucocorticoids
  • Macrolides
  • Muscarinic Antagonists
  • Quinolones
  • beta-Lactams
  • Clindamycin
  • Azithromycin