Anke Van Herck1, Anna E Frick2, Veronique Schaevers1, Annelies Vranckx3, Eric K Verbeken4, Bart M Vanaudenaerde1, Annelore Sacreas1, Tobias Heigl1, Arne P Neyrinck5, Dirk Van Raemdonck6, Lieven J Dupont1, Jonas Yserbyt1, Stijn E Verleden1, Geert M Verleden1, Robin Vos7. 1. Lung Transplant Unit, Department of Chronic Diseases, Metabolism & Ageing. 2. Lung Transplant Unit, Department of Chronic Diseases, Metabolism & Ageing; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium. 3. University Hospital Clinical Pharmacy, Leuven, Belgium. 4. Department of Imaging & Pathology, KU Leuven, Leuven, Belgium. 5. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. 6. Lung Transplant Unit, Department of Chronic Diseases, Metabolism & Ageing; Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium. 7. Lung Transplant Unit, Department of Chronic Diseases, Metabolism & Ageing. Electronic address: robin.vos@uzleuven.be.
Abstract
BACKGROUND:Chronic lung allograft dysfunction (CLAD) is the single most important factor limiting long-term survival after lung transplantation (LTx). Azithromycin has been shown to improve CLAD-free and long-term survival, yet the possible impact on early lung allograft function is unclear. METHODS: A prospective, randomized, double-blind, placebo-controlled trial of pre-transplant and prompt post-transplant azithromycin treatment was performed at the University Hospitals Leuven. In each arm, 34 patients, transplanted between October 2013 and October 2015, were included for analysis. Study drug was added to standard of care and was administered once before LTx (1,000 mg of azithromycin or placebo) and every other day from Day 1 until Day 31 after LTx (250 mg of azithromycin or placebo). Primary outcome was an anticipated 15% improvement of forced expiratory volume in 1 second (FEV1, percent predicted) during the first 3 months post-LTx. Secondary end-points included length of intubation, days on ventilator, duration of intensive care unit and hospital stay, prevalence and severity of primary graft dysfunction, acute rejection, infection, and CLAD-free and overall survival. RESULTS:FEV1 was not significantly different between the 2 groups (p = 0.41). Patients treated with azithromycin demonstrated less airway inflammation, with lower bronchoalveolar lavage (BAL) neutrophilia and BAL interleukin-8 protein levels at Day 30 (p = 0.09 and p = 0.04, respectively) and Day 90 (p = 0.002 and p = 0.08, respectively) after LTx. Other secondary outcomes were not significantly different between placebo and azithromycin groups. CONCLUSIONS:Pre-transplant and prompt post-transplant azithromycin treatment was not able to improve early lung allograft function. However, the known anti-inflammatory properties of azithromycin were confirmed (NCT01915082).
RCT Entities:
BACKGROUND:Chronic lung allograft dysfunction (CLAD) is the single most important factor limiting long-term survival after lung transplantation (LTx). Azithromycin has been shown to improve CLAD-free and long-term survival, yet the possible impact on early lung allograft function is unclear. METHODS: A prospective, randomized, double-blind, placebo-controlled trial of pre-transplant and prompt post-transplant azithromycin treatment was performed at the University Hospitals Leuven. In each arm, 34 patients, transplanted between October 2013 and October 2015, were included for analysis. Study drug was added to standard of care and was administered once before LTx (1,000 mg of azithromycin or placebo) and every other day from Day 1 until Day 31 after LTx (250 mg of azithromycin or placebo). Primary outcome was an anticipated 15% improvement of forced expiratory volume in 1 second (FEV1, percent predicted) during the first 3 months post-LTx. Secondary end-points included length of intubation, days on ventilator, duration of intensive care unit and hospital stay, prevalence and severity of primary graft dysfunction, acute rejection, infection, and CLAD-free and overall survival. RESULTS: FEV1 was not significantly different between the 2 groups (p = 0.41). Patients treated with azithromycin demonstrated less airway inflammation, with lower bronchoalveolar lavage (BAL) neutrophilia and BAL interleukin-8 protein levels at Day 30 (p = 0.09 and p = 0.04, respectively) and Day 90 (p = 0.002 and p = 0.08, respectively) after LTx. Other secondary outcomes were not significantly different between placebo and azithromycin groups. CONCLUSIONS: Pre-transplant and prompt post-transplant azithromycin treatment was not able to improve early lung allograft function. However, the known anti-inflammatory properties of azithromycin were confirmed (NCT01915082).
Authors: Siddhartha G Kapnadak; Eric D Morrell; Travis Hee Wai; Christopher H Goss; Pali D Shah; Christian A Merlo; Ramsey R Hachem; Kathleen J Ramos Journal: J Heart Lung Transplant Date: 2021-10-22 Impact factor: 10.247