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

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.

Overview of the study.

FIGURE 1

Patient flowchart. From 119 subjects initially screened, six subjects were excluded: withdrawal of consent (n=3), abnormal biochemical blood analysis (n=2) and history of angioedema (n=1). Finally, 113 subjects were randomised. Patients discontinued the study prematurely due to the following reasons: toxicity in four patients (3.5%) in the pirfenidone group and in three patients (2.7%) in the placebo group, and consent withdrawal in three patients (3.5%) in the pirfenidone group. FVC: forced vital capacity; ITT: intention-to-treat; mITT: modified intention-to-treat.

FIGURE 2

Mean difference in forced vital capacity (FVC) between visits 1 and 3. Error bars represent 95% confidence intervals.