Current state of clinical trials regarding lung transplant rejection

Background: Over the last several decades, the field of lung transplantation has made significant advances. Despite these advancements, morbidity and mortality rates are still high when compared to other solid organ transplants. Clinical trials have a significant role bringing new medications with better effects than their pre-decessors. Our study is critical in evaluating and tracking clinical trials involving rejection of lung transplant, with a focus on interventional therapeutic trials. Methods: On November 3, 2021, we searched clinicaltrial.gov for interventional clinical trials related to lung transplant rejection. A total of 39 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus, and their content reviewed and summarized. Results: The majority of trials were divided into completed (15 out of 39) and recruiting (12 out of 39). 17 trials had between 11 and 50 participants, and 8 had above 100. Only 1 trial lasted >10 years, and the average length of all trials was 3.6 years. The majority of trials were conducted in Europe/UK/Russia and the United States/ Canada (17 and 18 trials, respectively). The results were provided in 3 trials, and also published in 3, showing a decrease in the rate of patients reaching an endpoint after chronic rejection with liposomal aerosol cyclosporine, a decrease in their cytokines level, and an increase in their 5-year-survival rate compared to the oral conven-tional immunosuppressant, the benefit of sirolimus in decreasing the acute rejection rate and severity in com-parison to azathioprine, and its efficacy against cytomegalovirus infections. Other trials revealed the benefits of azithromycin in remarkably decreasing airways and systemic inflammation, with a concomitant decline in the risk of both BOS and CLAD; highlighting the deleterious effects of air pollution after transplantation surgery; and using the grading biopsy as a post-transplantation assessment tool. Conclusion: This study is a descriptive analysis of clinical trials targeting lung transplant rejection. This study shows the low number of trials, lack of variety in location and low publishing rates. Although focus of published trials was mainly towards azithromycin, bronchiolitis obliterans syndrome, air pollution, and biopsy in grading, a remarkable progress was realized concerning therapies, leading to less complications with a delay of chronic rejection onset, and an increase in overall survival. This sheds the light on the need for managing research efforts to fulfill any lack in specific domain, leading to new, effective therapies, and providing thereby much more benefit.