Optimising Azithromycin prevention treatment in COPD to reduce Exacerbation

Visit the OPACE website 

Research summary

Prophylactic azithromycin is recommended as a treatment to reduce the risk of COPD exacerbations on people with COPD at high risk of exacerbations. In clinical practice, there is much uncertainty in how to optimally use this valuable antibiotic in managing COPD. It is unknown whether azithromycin is effective beyond one-year of treatment; what happens when azithromycin is discontinued following a period of use; or temporarily discontinued over the summer when there are fewer exacerbations. Although, we do undertake these interventions in clinical practice, we currently have no evidence about their effects. We also don't know if there are differences in treatment responsiveness to azithromycin between subgroups of people with COPD.

The aim of the trial is to evaluate the benefits and risks of complete or seasonal discontinuation of azithromycin chemoprophylaxis vs continued treatment in people with stable COPD on ling-term azithromycin.

OPACE is randomised double-blinded, non-inferiority, adaptive-design pragmatic trial of 3 parallel arms:

  • complete discontinuation of prophylactic azithromycin
  • seasonal discontinuation (discontinue over the summer, active over the winter)
  • continued azithromycin prophylaxis as standard of care

During the OPACE trial, neither the participants nor the trial team will know which intervention (trial arm) the participant is allocated to. This will help to avoid any bias in the data collected.

Trial medication is delivered to participants' homes. Trial medication can be stopped if needed and participants restart their usual azithromycin if advised to. All participants will still be followed up in the trial. Participants are monitored during the trial with a combination of face-to-face appointments and telephone follow up. Face to face appointment can be conducted by telephone or video if facilities available.

Target recruitment is at least 1311 participants involving GP practices and hospitals across the UK.   

Main inclusion criteria

  • Be able and willing to provide informed consent.
  • Have an established clinical diagnosis of COPD and be receiving prophylactic azithromycin (or equivalent macrolide) for ≥ (at least) 3 months to reduce COPD exacerbations.
  • Have a self-reported smoking history of ≥ (at least) 10 pack years.
  • Be aged ≥ 40 years.
  • Have clinically stable COPD, i.e. no COPD exacerbation for at least 6 weeks.

Main exclusion criteria

  • Known hypersensitivity to any of the trial drugs or excipients.
  • Current breast feeding, pregnancy or planned pregnancy during trial.
  • Any medical history or clinically relevant abnormality that makes patient ineligible for inclusion because of a safety concern relating to continuing or discontinuing azithromycin or other considerations.
  • Known immunodeficiency requiring immunoglobulin/specific antibody therapy.
  • Azithromycin (or equal macrolide) prophylaxis prescribed for non-COPD condition.
  • Active participation in COPD CTIMP.

Chief investigator

Professor Ian Wilkinson


Contact details

Senior Clinical Trials Coordinator: Dr Zehra Yilmaz

Tel: 01223 336 806         Email: [email protected]