Chandelier
Senior Member (Voting Rights)
Randomized controlled trial of pirfenidone XR for patients with COVID-19 and exploration of effects on long-COVID incidence
Long-term follow-up showed a numerically lower incidence of long COVID symptoms in 1, 2, 3 and 4 symptom domains in the pirfenidone-XR group: symptoms in ≥4 domains were reported in 5% vs 21% of hospitalized patients. There were no unexpected safety signals.
These findings support further investigation of pirfenidone-XR in patients infected with SARS-CoV-2 and similar post-infectious syndromes characterized by persistent immune activation and tissue remodeling.
Web | DOI | International Journal of Infectious Diseases | Open Access
M, Tamez-Torres Karla; Karina, Aguilar Laura; Alejandro, Díaz-Mejía Bruno; Maria de la Luz, Morales-Ortega; E, Ramírez-González Luis; Ren, Highstrete; S, González-Cruz Adalberto; Esteban, Pérez-García; Vanessa, Hernández-Martínez Ingrid; Alejandra, Hernández-Delgado; Nadiel, Hernández-Aldana; A, Gorgonio Pedro; A, Núñez-Álvarez Carlos; F, Hernández-Ramírez Diego; A, Lara-García Eunice; Alfonso, Rumoroso-García Jose; Angelica, Nava-Linares; Axel, Cervantes-Sánchez; Mónica, Chapa-Ibargüengoitia; R, Valdez-Vazquez Rafael; Alfredo, Ponce-de León; Estuardo, Aguilar-Cordova; K, Aguilar Laura; David, Kershenobich-Stalnikowitz; Jose, Sifuentes-Osornio
Abstract
Objective
Evaluate safety and efficacy of extended-release pirfenidone (pirfenidone-XR), an anti-inflammatory and anti-fibrotic agent, as an early treatment for acute and long-term effects of COVID-19.Methods
This double-blinded, placebo-controlled trial randomized hospitalized and ambulatory COVID-19 patients in Mexico City 2:1 to pirfenidone-XR or placebo. The primary endpoint was recovery dynamics using a clinical severity 7-point ordinal scale; secondary and exploratory endpoints included long COVID incidence and safety. Planned enrollment was 801 patients to detect a 50% relative-risk reduction in key clinical outcomes.Results
Between May 2020 and May 2021, 367 patients were enrolled, approximately 50% of the target. Evolving standards of care resulted in early termination and lower-than-anticipated event rates, limiting statistical power. Time-to-recovery analyses suggested improved dynamics with pirfenidone-XR: both groups had 53% full recovery by week 1; an additional 33% vs 21% achieved it during week 2, and 97% vs 90% by week 4.Long-term follow-up showed a numerically lower incidence of long COVID symptoms in 1, 2, 3 and 4 symptom domains in the pirfenidone-XR group: symptoms in ≥4 domains were reported in 5% vs 21% of hospitalized patients. There were no unexpected safety signals.
Conclusions
Pirfenidone-XR was well tolerated and, although underpowered, demonstrated numerical trends of improved recovery and reduced long COVID risk.These findings support further investigation of pirfenidone-XR in patients infected with SARS-CoV-2 and similar post-infectious syndromes characterized by persistent immune activation and tissue remodeling.
Highlights
- Randomized placebo-controlled trial of extended-release pirfenidone XR in COVID-19
- Extended-release pirfenidone XR was well tolerated
- Recovery dynamics numerically favored pirfenidone XR
- Four-year follow-up assessed Long COVID across multiple domains
- Finding support further study of anti-inflammatory/antifibrotic therapy for COVID-19
Web | DOI | International Journal of Infectious Diseases | Open Access
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