Design and Rationale of Cytokine filtration in lung transplantation – a randomised, controlled, multicentre clinical trial (GLUSorb) (Preprint)

Lung transplantation is the only treatment option for end stage lung disease. Despite improvements, in LTx, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the mainchief factor in late mortality after lung transplantationLtx. Primary graft dysfunctionPGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen/fraction of inspired oxygen (P/F ratio). Increasing the P/F ratio is thus critical and has an direct impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. Yet, treatments for PGD are lacking. In a proof-of-concept pre-clinical porcine model of lung transplantationLTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study we successfully treated lung transplantationLTx patients with cytokine filtration (NCT05242289).The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving lung transplantation outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration.This study is a Swedish national interventional randomised controlled study involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with lung transplantation. Specifically, the study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a lung transplantation procedure, can lead to improved patient outcomes. The study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the post-transplantation course.The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which is slated to take place on August 28, 2023. The primary outcome measure that will be assessed in this research endeavor is the oxygenation ratio, a metric denoted as the highest P/F (PaO2/FiO2) ratio achieved by patients within a 72-hour timeframe following their lung transplantation procedure.We propose that cytokine filtration could enhance the overall outcomes of lung transplantation. Our hypothesis suggests potential improvements in lung transplantation outcome and patient care.Clinicaltrials.gov: NCT05526950. Medical Products Agency, Sweden (Dnr 5.1- 2023-23105).