A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019
Julio A Chirinos, Patricio Lopez-Jaramillo, Evangelos J Giamarellos-Bourboulis, Gonzalo H Dávila-Del-Carpio, Abdul Rahman Bizri, Jaime F Andrade-Villanueva, Oday Salman, Carlos Cure-Cure, Nelson R Rosado-Santander, Mario P Cornejo Giraldo, Luz A González-Hernández, Rima Moghnieh, Rapti Angeliki, María E Cruz Saldarriaga, Marcos Pariona, Carola Medina, Ioannis Dimitroulis, Charalambos Vlachopoulos, Corina Gutierrez, Juan E Rodriguez-Mori, Edgar Gomez-Laiton, Rosa Cotrina Pereyra, Jorge Luis Ravelo Hernández, Hugo Arbañil, José Accini-Mendoza, Maritza Pérez-Mayorga, Charalampos Milionis, Garyfallia Poulakou, Gregorio Sánchez, Renzo Valdivia-Vega, Mirko Villavicencio-Carranza, Ricardo J Ayala-García, Carlos A Castro-Callirgos, Rosa M Alfaro Carrasco, Willy Garrido Lecca Danos, Tiffany Sharkoski, Katherine Greene, Bianca Pourmussa, Candy Greczylo, Juan Ortega-Legaspi, Douglas Jacoby, Jesse Chittams, Paraskevi Katsaounou, Zoi Alexiou, Styliani Sympardi, Nancy K Sweitzer, Mary Putt, Jordana B Cohen, FERMIN Investigators, Ciro Barrantes Alarcón, Denisse Marylyn Mendoza Sanchez, Eduardo Francisco Bernales Salas, Claudia Jesús Chamby Díaz, Ursula Milagros Vargas Gómez, Cynthia Daniela Salinas Herrera, Naldy Lidia Barriga Triviños, Johanna Carolina Coacalla Guerra, Evelyn Marrón Veria, Preethi William, Hugo Espinoza-Rojas, Irwing Renato Benites-Flores, Pedro Antonio Segura-Saldaña, Julio A Chirinos, Patricio Lopez-Jaramillo, Evangelos J Giamarellos-Bourboulis, Gonzalo H Dávila-Del-Carpio, Abdul Rahman Bizri, Jaime F Andrade-Villanueva, Oday Salman, Carlos Cure-Cure, Nelson R Rosado-Santander, Mario P Cornejo Giraldo, Luz A González-Hernández, Rima Moghnieh, Rapti Angeliki, María E Cruz Saldarriaga, Marcos Pariona, Carola Medina, Ioannis Dimitroulis, Charalambos Vlachopoulos, Corina Gutierrez, Juan E Rodriguez-Mori, Edgar Gomez-Laiton, Rosa Cotrina Pereyra, Jorge Luis Ravelo Hernández, Hugo Arbañil, José Accini-Mendoza, Maritza Pérez-Mayorga, Charalampos Milionis, Garyfallia Poulakou, Gregorio Sánchez, Renzo Valdivia-Vega, Mirko Villavicencio-Carranza, Ricardo J Ayala-García, Carlos A Castro-Callirgos, Rosa M Alfaro Carrasco, Willy Garrido Lecca Danos, Tiffany Sharkoski, Katherine Greene, Bianca Pourmussa, Candy Greczylo, Juan Ortega-Legaspi, Douglas Jacoby, Jesse Chittams, Paraskevi Katsaounou, Zoi Alexiou, Styliani Sympardi, Nancy K Sweitzer, Mary Putt, Jordana B Cohen, FERMIN Investigators, Ciro Barrantes Alarcón, Denisse Marylyn Mendoza Sanchez, Eduardo Francisco Bernales Salas, Claudia Jesús Chamby Díaz, Ursula Milagros Vargas Gómez, Cynthia Daniela Salinas Herrera, Naldy Lidia Barriga Triviños, Johanna Carolina Coacalla Guerra, Evelyn Marrón Veria, Preethi William, Hugo Espinoza-Rojas, Irwing Renato Benites-Flores, Pedro Antonio Segura-Saldaña
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).
Conflict of interest statement
In the last 2 years, J.B.C. has received research grants from the National Institutes of Health and American Heart Association. In the last 2 years, J.A.C. has received consulting honoraria from Sanifit, Bristol Myers Squibb, Merck, Edwards Lifesciences, Bayer, JNJ, the University of Delaware, and research grants from the National Institutes of Health, Abbott, Microsoft, Fukuda-Denshi and Bristol Myers Squibb. J.A.C. has received compensation from the American Heart Association and the American College of Cardiology for editorial roles, and visiting speaker honoraria from Washington University, University of Utah, the Japanese Association for Cardiovascular Nursing and the Korean Society of Cardiology. E.J.G. has received honoraria from Abbott CH, bioMérieux, Brahms, GSK, InflaRx, Sobi and XBiotech; independent educational grants from Abbott CH, AxisShield, bioMérieux, InflaRx, Johnson & Johnson, MSD, Sobi and XBiotech; and funding from the Horizon 2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis). In the last 2 years, N.K.S. has received compensation from the American Heart Association for editorial duties. The remaining authors declare no competing interests.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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Source: PubMed