Lindstedt Sandra, Silverborn Martin, Lannemyr Lukas, Pierre Leif, Larsson Hillevi, Grins Edgars, Hyllen Snejana, Dellgren Goran, Magnusson Jesper
Skane University Hospital, Lund, Sweden.
Sahlgrenska University Hospital, Gothenburg, Sweden.
JMIR Res Protoc. 2023 Dec 13;12:e52553. doi: 10.2196/52553.
Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO)/fraction of inspired oxygen (FiO). Increasing the PaO/FiO ratio is thus critical and has an 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. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289).
The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx 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 randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the posttransplantation course.
The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which was 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 PaO/FiO ratio achieved by patients within a 72-hour timeframe following their LTx procedure.
We propose that cytokine filtration could enhance the overall outcomes of LTx. Our hypothesis suggests potential improvements in LTx outcome and patient care.
ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52553.
肺移植（LTx）是终末期肺病的唯一治疗选择。尽管有所改善，但原发性移植肺功能障碍（PGD）仍然是早期死亡的主要原因，并促成慢性移植肺功能障碍，这是肺移植术后晚期死亡的主要因素。PGD在术后72小时内发生，并损害肺的氧合能力，以氧分压（PaO）/吸入氧分数（FiO）来衡量。因此，提高PaO/FiO比值至关重要，且对生存率有影响。目前普遍缺乏针对PGD的有效治疗方法。当移植肺不被受者免疫系统接受时，会引发全身炎症反应，细胞因子在引发、放大和维持导致PGD的炎症过程中起关键作用。细胞因子过滤可从循环中去除这些细胞因子，从而减轻炎症。在一项肺移植的概念验证临床前猪模型研究中，细胞因子过滤改善了氧合并降低了PGD发生率。在一项可行性研究中，我们成功地对接受肺移植的患者进行了细胞因子过滤治疗（ClinicalTrials.gov；NCT05242289）。
本临床试验的目的是证明与未进行细胞因子过滤的标准治疗相比，细胞因子过滤在改善肺移植结局方面的优越性，基于其对氧合比、炎症标志物血浆水平、PGD发生率和严重程度、肺功能、肾功能、生存率和生活质量的影响。
本研究是一项瑞典全国性介入性随机对照试验，涉及116名患者。其主要目的是研究细胞因子过滤与肺移植联合使用时的潜在益处。具体而言，本研究旨在确定在肺移植手术初始24小时内进行为期12小时的细胞因子过滤应用是否能改善患者结局。本研究旨在评估患者恢复和整体健康的各个方面，以确定该干预措施对移植后病程的潜在积极影响。
本研究的患者招募过程计划在2023年8月28日进行的现场启动访问之后开始。本研究将评估的主要结局指标是氧合比，该指标指患者在肺移植手术后72小时内达到的最高PaO/FiO比值。
我们认为细胞因子过滤可改善肺移植的总体结局。我们的假设表明肺移植结局和患者护理可能会得到改善。
ClinicalTrials.gov NCT05526950；https://www.clinicaltrials.gov/study/NCT05526950。
国际注册报告识别码（IRRID）：PRR1-10.2196/52553。
