A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation

Eur Respir J. 2011 Jan;37(1):164-72. doi: 10.1183/09031936.00068310. Epub 2010 Jun 18.

Abstract

Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s (FEV₁) in chronic rejection or bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Azithromycin prophylaxis might prevent BOS. A double-blind randomised controlled trial of azithromycin (n = 40) or placebo (n = 43), initiated at discharge and administered three times a week for 2 yrs, was performed in 2005-2009 at the Leuven University Hospital (Leuven, Belgium). Primary end-points were BOS-free and overall survival 2 yrs after LTx; secondary end-points were acute rejection, lymphocytic bronchiolitis and pneumonitis rate, prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux, and change in FEV₁, airway and systemic inflammation over time. Patients developing BOS were assessed for change in FEV₁ with open-label azithromycin. BOS occurred less in patients receiving azithromycin: 12.5 versus 44.2% (p = 0.0017). BOS-free survival was better with azithromycin (hazard ratio 0.27, 95% CI 0.092-0.816; p = 0.020). Overall survival, acute rejection, lymphocytic bronchiolitis, pneumonitis, colonisation and reflux were comparable between groups. Patients receiving azithromycin demonstrated better FEV₁ (p = 0.028), and lower airway neutrophilia (p = 0.015) and systemic C-reactive protein levels (p = 0.050) over time. Open-label azithromycin for BOS improved FEV₁ in 52.2% patients. No serious adverse events were noted. Azithromycin prophylaxis attenuates local and systemic inflammation, improves FEV₁ and reduces BOS 2 yrs after LTx.

Trial registration: ClinicalTrials.gov NCT01009619.

Publication types

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

MeSH terms

  • Adult
  • Azithromycin / therapeutic use*
  • Bronchiolitis Obliterans / prevention & control
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation
  • Lung Transplantation / methods*
  • Male
  • Middle Aged
  • Placebos
  • Proportional Hazards Models
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Placebos
  • Azithromycin

Associated data

  • ClinicalTrials.gov/NCT01009619
  • ISRCTN/ISRCTN36220396