Pirfenidone to prevent fibrosis in acute respiratory distress syndrome: The PIONEER study protocol.

Summary

This ongoing multicenter, double-blind RCT will randomize 130 invasively ventilated ARDS patients to pirfenidone versus placebo for up to 28 days, with ventilator-free days at day 28 as the primary outcome. Secondary endpoints include ICU/hospital-free days, mortality, HRCT fibroproliferation markers, and quality of life.

Key Findings

• First multicenter, double-blind, placebo-controlled RCT testing pirfenidone in ARDS (N=130).
• Primary outcome: ventilator-free days at day 28; secondary outcomes include ICU/hospital-free days and mortality.
• Fibroproliferation assessed by HRCT at ICU discharge; trial registered (NCT05075161) with intention-to-treat analysis.

Clinical Implications

Clinicians should be aware of ongoing enrollment and avoid off-trial pirfenidone use; if efficacy is demonstrated, early antifibrotic therapy may become part of ARDS management, guided by HRCT and clinical endpoints.

Limitations

• Protocol paper: no clinical results yet; actual effect size and safety are unknown.
• Modest sample size (N=130) may limit power for mortality and subgroup analyses; ARDS heterogeneity may dilute treatment effect.

Future Directions

If efficacy signals emerge, proceed to larger phase III trials, enrich for fibroproliferative phenotypes using imaging/biomarkers, and explore timing, dosing, and combination strategies with lung-protective ventilation.