1. A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019
- Author
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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, and Jordana Cohen
- 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.
- Published
- 2022
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