Current state of clinical trials on xenograft.

BACKGROUND: Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field. METHODS: In December 2022, we searched clinicaltrial.gov for interventional clinical trials related to xenograft of skin, pancreas, bone marrow, aortic valve and kidney. A total of 14 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus. Content of trials was reviewed and summarized. RESULTS: Only 14 clinical trials met our study's criteria. The majority were completed, and most of the trials' enrolment was between 11 and 50 participants. Nine trials used a xenograft of porcine origin. Six trials targeted skin xenotransplantation, four targeted ß-cells, two targeted bone marrow and one trial targeted each of the kidney and aortic valve. The average length of trials was 3.38 years. Four trials were conducted in the United States and two trials in each of Brazil, Argentina and Sweden. Of all the included trials, none had any results provided and only three had published work. Phases I, III, and IV had only one trial each. A total of 501 participants were enrolled in these trials. CONCLUSION: This study sheds the light on the current state of clinical trials on xenograft. Characteristically, trials on this field are of low number, low enrolment, short duration, few related publications and no published results. Porcine organs are the most used in these trials, and skin is the most studied organ. An extension of the literature is highly needed due to the variety of conflicts mentioned. Overall, this study sheds the light on the necessity of managing research efforts, leading to the initiation of more trials targeting the field of xenotransplantation.

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 predecessors. 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 conventional immunosuppressant, the benefit of sirolimus in decreasing the acute rejection rate and severity in comparison 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.