Respiratory Trials·org

Bronchiectasis · Long-term macrolides

BLESS randomised trial

Effect of long-term, low-dose erythromycin on pulmonary exacerbations in bronchiectasis

BLESS trial design and results
Design Randomised, double-blind, placebo-controlled trial
Treatment Erythromycin ethylsuccinate 400 mg twice daily
Control Placebo
Population 117 randomised patients with bronchiectasis, of 679 screened; 107 (91.5%) completed
Follow-up 48 weeks
Primary endpoint Protocol-defined pulmonary exacerbations
Result Erythromycin reduced exacerbations from 1.97 (95% CI 1.45 to 2.48) to 1.29 (0.93 to 1.65) per patient per year — incidence rate ratio 0.57 (95% CI 0.42 to 0.77, p=0.003) — and did so in the prespecified subgroup with Pseudomonas aeruginosa airway infection (mean difference 1.32, p=0.02). Twenty-four-hour sputum production fell by a median of 4.3 g.
Secondary endpoints Sputum volume, lung function, macrolide resistance in commensal organisms

Among patients with non-CF bronchiectasis, the 12-month use of erythromycin compared with placebo resulted in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance.

The trial authors, in the published abstract

How it has aged

The third of the macrolide trials, with BAT and EMBRACE, and the only one to demonstrate benefit specifically in Pseudomonas colonisation — the group most often assumed to need inhaled antibiotics instead. It also documented increased macrolide resistance among commensal organisms, which is the cost every one of these trials flags and none resolves.

Publications

Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial

Serisier DJ, Martin ML, McGuckin MA, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 2013 Mar 27;309(12):1260-7.

  • Exacerbations reduced from 1.97 to 1.29 per patient per year
  • Benefit retained in the Pseudomonas-infected subgroup
  • Reduced sputum production, with increased macrolide resistance in commensals