Transplant Trial Watch

Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

Ruttens D, Verleden SE, et al.

American Journal of Transplantation 2016; 16(1): 254-261.

To evaluate the long-term effects of prophylactic azithromycin therapy post lung transplantation in view of the recently updated classification system for chronic lung allograft dysfunction (CLAD).

Participants were randomized to receive either azithromycin (250mg) three times per week, or placebo.

83 single-lung, bilateral lung or heart–lung transplant recipients >18 years of age, previously included in a randomized controlled trial of azithromycin versus placebo*

Outcomes measured were CLAD, graft loss, pulmonary function and functional exercise capacity.

7 years

CET Conclusions
This manuscript reports a long-term, retrospective analysis of an RCT comparing prophylactic azithromycin to placebo in lung transplant recipients. Azithromycin has anti-inflammatory and immunomodulatory properties and was shown in an earlier analysis to improve freedom from bronchiolitis obliterans early after lung transplant. Since then, the classification of chronic lung allograft dysfunction (CLAD) has been revised and the authors here provide a retrospective analysis of the 7-year follow-up of the patients in the trial, using the new CLAD classification. The analysis demonstrates a significant reduction in the incidence of CLAD (and improved CLAD free survival time) with prophylactic azithromycin. Long-term pulmonary function and functional exercise capacity were also significantly better in the treatment arm. Data regarding tacrolimus levels are missing from the manuscript – there are some case reports of interaction between azithromycin and tacrolimus, and erratic tacrolimus levels have been shown to be predictive for development of CLAD. This is a relatively small, retrospective analysis and so should be regarded as exploratory, but nonetheless provides some evidence of a role for prophylactic azithromycin in these patients.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Quality notes
Previously assessed as *Vos R, et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J 2011; 37: 164–172.

Trial registration - NCT01009619

Funding source
Non-industry funded