Pirfenidone in post-COVID-19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomised clinical trial

Eur Respir J. 2025 Apr 24;65(4):2402249. doi: 10.1183/13993003.02249-2024. Print 2025 Apr.

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.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • COVID-19 Drug Treatment*
  • COVID-19* / complications
  • Double-Blind Method
  • Exercise Tolerance
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Lung / diagnostic imaging
  • Male
  • Middle Aged
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / etiology
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Quality of Life
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vital Capacity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • pirfenidone
  • Pyridones