Pirfenidone in post-COVID-19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomised clinical trial
Guadalupe Bermudo, Belén del Río, Vanesa Vicens‐Zygmunt, Jaume Bordas-Martínez, Marta Hernández, Claudia Valenzuela, Rosalía Laporta, Juan Rigual Bobillo, Karina Portillo, Paloma Millan‐Billi, Eva Balcells, Diana Badenes‐Bonet, Santiago Bolívar, José-Antonio Rodríguez-Portal, Cecilia López Ramirez, Laura Tomás, Koral Fernández de Roitegi, Jacobo Sellarés, Diego Castillo, Jessica González, Silvia Barril, Yasmina Gutiérrez-Rodríguez, Paloma Caballero, Javier Alarcón, Judith Peñafiel, José Sanz‐Santos, Rosana Blavia, Cristina Caupena, Pilar Segovia, Salud Santos, Anna Ferrer, M. Badia, Pilar Hereu, Mireya Fuentes, Ana Montes‐Worboys, Tomás Franquet, Patricio Luburich, María Molina‐Molina
Abstract
Background 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. Methods 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. Results 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 −2 . The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% versus 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. Conclusions The overall improvements in lung function and HRCT fibrotic score after 6 months with pirfenidone were not significantly different than with placebo.