{"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}
引用次数: 0
Abstract
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.