Bermudo-Peloche Guadalupe, Del Rio Belén, Vicens-Zygmunt Vanesa, Bordas-Martinez Jaume, Hernández Marta, Valenzuela Claudia, Laporta Rosalía, Rigual Bobillo Juan, Portillo Karina, Millán-Billi Paloma, Balcells Eva, Badenes-Bonet Diana, Bolivar Santi, Rodríguez-Portal José-Antonio, López Ramirez Cecilia, Tomás Laura, Fernández de Roitegi Koral, Sellarés Jacobo, Castillo Diego, González Jessica, Barril Silvia, Gutiérrez-Rodríguez Yasmina, Caballero Paloma, Alarcon Javier, Peñafiel Judith, Sanz-Santos Jose, Blavia Rosana, Caupena Cristina, Segovia Pilar, Santos-Pérez Salud, Ferrer-Artola Anna, Badia Maria B, Hereu Pilar, Fuentes Mireya, Montes-Worboys Ana, Franquet Tomás, Luburich Patricio, Molina-Molina María
Interstitial Lung Disease Unit, Respiratory Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain.
National Network of Research in Respiratory Diseases (CIBERES), Barcelona, Spain.
Eur Respir J. 2025 Apr 24;65(4). doi: 10.1183/13993003.02249-2024. Print 2025 Apr.
Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia were evaluated.
This was a phase 2, double-blind, placebo-controlled, Spanish multicentre clinical trial. Patients were randomised to receive pirfenidone or placebo (2:1) for 24 weeks. The primary end-point was the proportion of patients that improved, considered when percentage change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score on chest high-resolution computed tomography (HRCT). Secondary end-points included health-related quality of life (HRQoL), exercise capacity and drug safety profile.
From 119 eligible patients, 113 were randomised and 103 were analysed (pirfenidone n=69 and placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and mean body mass index was 29 kg·m. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% 82.3%, respectively). The mean predicted FVC increased by 12.74±20.6% with pirfenidone and 4.35±22.3% with placebo (p=0.071), and the HRCT (%) fibrotic score decreased by 5.44±3.69% with pirfenidone and 2.57±2.59% with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in the pirfenidone group and 39.4% in the placebo group). Exercise capacity, adverse events and hospitalisations were similar between groups. No deaths were reported.
The overall improvements in lung function and HRCT fibrotic score after 6 months with pirfenidone were not significantly different than with placebo.
重症新型冠状病毒肺炎（COVID-19）患者可能会发展为肺纤维化。吡非尼酮是一种被批准用于特发性肺纤维化的抗纤维化药物。本研究评估了吡非尼酮对重症COVID-19肺炎康复后出现纤维化间质性肺改变患者的疗效和安全性。
这是一项2期、双盲、安慰剂对照、西班牙多中心临床试验。患者被随机分为接受吡非尼酮或安慰剂（2:1）治疗24周。主要终点是病情改善的患者比例，定义为用力肺活量（FVC）百分比变化≥10%和/或胸部高分辨率计算机断层扫描（HRCT）纤维化评分有任何降低。次要终点包括健康相关生活质量（HRQoL）、运动能力和药物安全性。
119例符合条件的患者中，113例被随机分组，103例接受分析（吡非尼酮组n = 69，安慰剂组n = 34）。大多数患者为男性（73.5%），正在接受低剂量泼尼松治疗；平均年龄为63.7岁，平均体重指数为29kg·m²。吡非尼酮组和安慰剂组病情改善的患者百分比相似（分别为79.7%和82.3%）。吡非尼酮组平均预测FVC增加12.74±20.6%，安慰剂组增加4.35±22.3%（p = 0.071）；吡非尼酮组HRCT纤维化评分降低5.44±3.69%，安慰剂组降低2.57±2.59%（p = 0.52）。HRQoL的临床意义改善在两组间无统计学差异（吡非尼酮组为55.2%，安慰剂组为39.4%）。两组间运动能力、不良事件和住院情况相似。未报告死亡病例。
吡非尼酮治疗6个月后肺功能和HRCT纤维化评分的总体改善与安慰剂相比无显著差异。
