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A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019

Authors :
Julio Chirinos
Patricio Lopez-Jaramillo
Evangelos Giamarellos-Bourboulis
Gonzalo Dávila-del-Carpio
Abdul Bizri
Jaime Andrade-Villanueva
Oday Salman
Carlos Cure-Cure
Nelson Rosado-Santander
Mario Cornejo Giraldo
Luz González-Hernández
Rima Moghnieh
Rapti Angeliki
María Cruz Saldarriaga
Marcos Pariona
Carola Medina
Ioannis Dimitroulis
Charalambos Vlachopoulos
Corina Gutierrez
Juan Rodriguez-Mori
Edgar Gomez-Laiton
Rosa Pereyra
Jorge Ravelo Hernández
Hugo Arbañil
José Accini-Mendoza
Maritza Pérez-Mayorga
Haralampos Milionis
Garyfallia Poulakou
Gregorio Sánchez
Renzo Valdivia-Vega
Mirko Villavicencio-Carranza
Ricardo Ayala-Garcia
Carlos Castro-Callirgos
Rosa Alfaro Carrasco
Willy Lecca Danos
Tiffany Sharkoski
Katherine Greene
Bianca Pourmussa
Candy Greczylo
Jesse Chittams
Paraskevi Katsaounou
Zoi Alexiou
Styliani Sympardi
Nancy Sweitzer
Mary Putt
Jordana Cohen
Publication Year :
2022
Publisher :
Research Square Platform LLC, 2022.

Abstract

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro. Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m2, and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....6251da34088b9d7ee7bed26c7bd590a5
Full Text :
https://doi.org/10.21203/rs.3.rs-1933913/v1