{"title":"针对慢性排斥患者的吡非尼酮随机试验(STOP-CLAD 研究)结果","authors":"","doi":"10.1016/j.healun.2024.05.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Chronic lung allograft<span> dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone<span> on quantitative radiographic and pulmonary function assessment in patients with CLAD.</span></span></p></div><div><h3>Methods</h3><p><span><span><span>We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD. Randomization was stratified by CLAD phenotype. The primary outcome for this study was change in radiographic assessment of </span>small airways disease, quantified as percentage of lung volume using parametric response mapping analysis of </span>computed tomography scans (PRM</span><sup>fSAD</sup><span>); secondary outcomes included change in forced expiratory volume in 1 second (FEV</span><sub>1</sub><span>), change in forced vital capacity (FVC), and change in radiographic quantification of parenchymal disease (PRM</span><sup>PD</sup>). Linear mixed models were used to evaluate the treatment effect on outcome measures.</p></div><div><h3>Results</h3><p><span>The goal enrollment of 60 patients was not met due to the coronavirus disease of 2019 pandemic, with 23 patients included in the analysis. There was no significant difference over the study period between the pirfenidone vs placebo groups with regards to the observed change in PRM</span><sup>fSAD</sup> (+4.2% vs −0.4%; <em>p</em> = 0.22), FEV<sub>1</sub> (−3.5% vs −3.6%; <em>p</em> = 0.97), FVC (−1.9% vs −4.6%; <em>p</em> = 0.41), or PRM<sup>PD</sup> (−0.6% vs −2.5%; <em>p</em><span> = 0.30). The study treatment tolerance and adverse events were generally similar between the pirfenidone and placebo groups.</span></p></div><div><h3>Conclusions</h3><p>Pirfenidone had no apparent impact on radiographic evidence of allograft dysfunction or pulmonary function decline in a single-center randomized trial of CLAD patients that did not meet enrollment goals but had an acceptable tolerance and side-effect profile.</p></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study)\",\"authors\":\"\",\"doi\":\"10.1016/j.healun.2024.05.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Chronic lung allograft<span> dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone<span> on quantitative radiographic and pulmonary function assessment in patients with CLAD.</span></span></p></div><div><h3>Methods</h3><p><span><span><span>We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD. Randomization was stratified by CLAD phenotype. The primary outcome for this study was change in radiographic assessment of </span>small airways disease, quantified as percentage of lung volume using parametric response mapping analysis of </span>computed tomography scans (PRM</span><sup>fSAD</sup><span>); secondary outcomes included change in forced expiratory volume in 1 second (FEV</span><sub>1</sub><span>), change in forced vital capacity (FVC), and change in radiographic quantification of parenchymal disease (PRM</span><sup>PD</sup>). Linear mixed models were used to evaluate the treatment effect on outcome measures.</p></div><div><h3>Results</h3><p><span>The goal enrollment of 60 patients was not met due to the coronavirus disease of 2019 pandemic, with 23 patients included in the analysis. There was no significant difference over the study period between the pirfenidone vs placebo groups with regards to the observed change in PRM</span><sup>fSAD</sup> (+4.2% vs −0.4%; <em>p</em> = 0.22), FEV<sub>1</sub> (−3.5% vs −3.6%; <em>p</em> = 0.97), FVC (−1.9% vs −4.6%; <em>p</em> = 0.41), or PRM<sup>PD</sup> (−0.6% vs −2.5%; <em>p</em><span> = 0.30). The study treatment tolerance and adverse events were generally similar between the pirfenidone and placebo groups.</span></p></div><div><h3>Conclusions</h3><p>Pirfenidone had no apparent impact on radiographic evidence of allograft dysfunction or pulmonary function decline in a single-center randomized trial of CLAD patients that did not meet enrollment goals but had an acceptable tolerance and side-effect profile.</p></div>\",\"PeriodicalId\":15900,\"journal\":{\"name\":\"Journal of Heart and Lung Transplantation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Heart and Lung Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S105324982401684X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Heart and Lung Transplantation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S105324982401684X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景慢性肺移植功能障碍(CLAD)是导致移植后长期不良预后的主要原因,表现为小气道纤维化重塑和/或胸膜下纤维细胞增生。本研究评估了吡非尼酮对 CLAD 患者的定量放射学和肺功能评估的影响。根据 CLAD 表型进行了分层随机化。这项研究的主要结果是小气道疾病放射学评估的变化,使用计算机断层扫描参数反应映射分析(PRMfSAD)量化为肺容积的百分比;次要结果包括1秒用力呼气容积(FEV1)的变化、用力生命容量(FVC)的变化和实质疾病放射学量化(PRMPD)的变化。结果由于2019年冠状病毒病的大流行,60名患者的入组目标未能实现,23名患者被纳入分析。在研究期间,吡非尼酮组与安慰剂组在PRMfSAD(+4.2% vs -0.4%;p = 0.22)、FEV1(-3.5% vs -3.6%;p = 0.97)、FVC(-1.9% vs -4.6%;p = 0.41)或PRMPD(-0.6% vs -2.5%;p = 0.30)的观察变化方面无明显差异。结论在一项针对 CLAD 患者的单中心随机试验中,吡非尼酮对异体移植功能障碍的影像学证据或肺功能下降无明显影响,该试验未达到入组目标,但其耐受性和副作用情况可以接受。
Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study)
Background
Chronic lung allograft dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone on quantitative radiographic and pulmonary function assessment in patients with CLAD.
Methods
We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD. Randomization was stratified by CLAD phenotype. The primary outcome for this study was change in radiographic assessment of small airways disease, quantified as percentage of lung volume using parametric response mapping analysis of computed tomography scans (PRMfSAD); secondary outcomes included change in forced expiratory volume in 1 second (FEV1), change in forced vital capacity (FVC), and change in radiographic quantification of parenchymal disease (PRMPD). Linear mixed models were used to evaluate the treatment effect on outcome measures.
Results
The goal enrollment of 60 patients was not met due to the coronavirus disease of 2019 pandemic, with 23 patients included in the analysis. There was no significant difference over the study period between the pirfenidone vs placebo groups with regards to the observed change in PRMfSAD (+4.2% vs −0.4%; p = 0.22), FEV1 (−3.5% vs −3.6%; p = 0.97), FVC (−1.9% vs −4.6%; p = 0.41), or PRMPD (−0.6% vs −2.5%; p = 0.30). The study treatment tolerance and adverse events were generally similar between the pirfenidone and placebo groups.
Conclusions
Pirfenidone had no apparent impact on radiographic evidence of allograft dysfunction or pulmonary function decline in a single-center randomized trial of CLAD patients that did not meet enrollment goals but had an acceptable tolerance and side-effect profile.
期刊介绍:
The Journal of Heart and Lung Transplantation, the official publication of the International Society for Heart and Lung Transplantation, brings readers essential scholarly and timely information in the field of cardio-pulmonary transplantation, mechanical and biological support of the failing heart, advanced lung disease (including pulmonary vascular disease) and cell replacement therapy. Importantly, the journal also serves as a medium of communication of pre-clinical sciences in all these rapidly expanding areas.