Respiratory Trials·org

Asthma · Long-term macrolides

AMAZES

Asthma and Macrolides: the Azithromycin Efficacy and Safety study

AMAZES trial design and results
Design Randomised, double-blind, placebo-controlled, parallel-group trial
Treatment Azithromycin 500 mg three times per week for 48 weeks
Control Placebo
Population 420 adults with symptomatic asthma despite inhaled steroid and long-acting bronchodilator
Inclusion criteria Aged 18 or over, symptomatic asthma despite inhaled corticosteroid and long-acting bronchodilator, no hearing impairment and no prolongation of the corrected QT interval.
Follow-up 48 weeks
Primary endpoint Rate of total (severe and moderate) asthma exacerbations, and asthma-related quality of life
Result Exacerbations 1.07 per patient-year (95% CI 0.85 to 1.29) with azithromycin versus 1.86 (1.54 to 2.18) with placebo — incidence rate ratio 0.59 (0.47 to 0.74), p<0.0001. At least one exacerbation occurred in 44% versus 61% (p<0.0001). Quality of life improved by 0.36 units (0.21 to 0.52, p=0.001). Diarrhoea affected 34% versus 19% (p=0.001).
Secondary endpoints Proportion exacerbating, asthma-related quality of life, adverse effects

Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks. Azithromycin might be a useful add-on therapy in persistent asthma.

The trial authors, in the published abstract

How it has aged

The strongest evidence for macrolides in asthma, and it works across eosinophilic and non-eosinophilic disease — which makes it one of the few options for the neutrophilic patient no biologic will help. Its enrolment criteria are the practical caveat: hearing and QT interval were screened, and should be in practice too, as in MACRO for COPD.

Publications

Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial

Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet 2017 Aug 12;390(10095):659-668.

  • 41% reduction in the rate of moderate and severe exacerbations
  • Proportion having any exacerbation fell from 61% to 44%
  • Clinically meaningful gain in asthma quality of life
  • Diarrhoea nearly doubled