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A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019

2022; Nature Portfolio; Volume: 4; Issue: 12 Linguagem: Inglês

10.1038/s42255-022-00698-3

2522-5812

Julio A. Chirinos, Patricio López‐Jaramillo, Evangelos J. Giamarellos‐Bourboulis, Gonzalo Dávila-Del-Carpio, Abdul Rahman Bizri, Jaime Andrade‐Villanueva, Oday Salman, Carlos Cure-Cure, Nelson R. Rosado‐Santander, Mario P. Cornejo Giraldo, Luz Alicia González-Hernández, Rima Moghnieh, Rapti Angeliki, María Cruz, Marcos Pariona, C. Medina, J. Dimitroulis, Charalambos Vlachopoulos, Corina Gutierrez, Juan E. Rodríguez-Mori, Edgar Gomez-Laiton, Rosa Cotrina Pereyra, Jorge Luis Ravelo Hernández, Hugo Arbañil, José Accini-Mendoza, Maritza Pérez-Mayorga, Haralampos Milionis, Garyphallia Poulakou, Gregorio Sánchez, Renzo Valdivia-Vega, Mirko Villavicencio-Carranza, Ricardo Ayala, Carlos Augusto 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 Κatsaounou, Zoi Alexiou, Styliani Sympardi, Nancy K. Sweitzer, Mary Putt, Jordana B. Cohen, 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 R. Benites-Flores, Pedro Segura-Saldaña,

SARS-CoV-2 detection and testing

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 ). Fenofibrate has been shown to inhibit SARS-CoV-2 replication in vitro. Results from a randomized clinical trial show that treating patients with COVID-19 with fenofibrate has no significant effect on clinically relevant outcomes.