Pirfenidone in post-COVID19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomized 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 was evaluated.

Methods: Phase 2, double-blind, placebo-controlled, Spanish multicenter clinical trial randomized to receive pirfenidone or placebo (2:1) for 24-weeks. The primary endpoint was the proportion of patients that improved, considered when percent change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score chest high-resolution computed tomography (HRCT). Secondary endpoints included health-related quality of life (HRQoL), exercise capacity, and drug safety profile.

Results: From 119 eligible patients, 113 were randomized and 103 were analyzed (pirfenidone n=69, placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and 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 12.74 (20.6) with pirfenidone and 4.35 (22.3) with placebo (p=0.071), and the HRCT (%) fibrotic score reduced 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 pirfenidone and 39.4% in placebo group, respectively). Exercise capacity, adverse events and hospitalizations were similar between groups. No deaths were reported.

Conclusions: The overall improvement in lung function and the HRCT fibrotic score after 6 months with pirfenidone was not significantly different than placebo.