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Randomized Controlled Trial
. 2024 Sep;43(9):1468-1477.
doi: 10.1016/j.healun.2024.05.013. Epub 2024 May 23.

Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study)

Michael P Combs  1 , Elizabeth A Belloli  1 , Nicolas Gargurevich  2 , Kevin R Flaherty  1 , Susan Murray  2 , Craig J Galbán  3 , Vibha N Lama  4
Affiliations
Randomized Controlled Trial

Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study)

Michael P Combs et al. J Heart Lung Transplant. 2024 Sep.

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.

Keywords: CLAD; antifibrotic therapy; chronic lung allograft dysfunction; clinical trial; pirfenidone.

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Conflict of interest statement

Disclosure statement The authors report the following financial conflicts of interest: Consulting fees from Roche/Genentech, Bellerophon, Respivant, Shionogi, DevPro, AstraZeneca, Pure Health, Horizon, FibroGen, Sun Pharmaceuticals, Pliant, United Therapeutics, Arrowhead, Lupin, Polarean, PureTech, Trevi, CSL Behring, Daewoong, Dispersol, Immunet, NeRRe Therapeutics, Insilco, Vicore, Glaxo Smith Kline, and Merck (all K.R.F.), RRD International LLC (S.M.), Coinventor of PRM currently licensed to Imbio (C.J.G.). We thank all the patients who generously participated in this research, to the University of Michigan research coordinator team, and Dennis M. Lyu, MD, who served as the data safety monitor for the study. This investigator-initiated clinical trial was funded by Genentech Inc. (San Francisco, CA). The funders did not participate in data collection, analysis, or preparation of the manuscript, tables, or figures.

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