TY - JOUR
T1 - A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019
AU - the FERMIN Investigators
AU - Chirinos, Julio A.
AU - Lopez-Jaramillo, Patricio
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Dávila-del-Carpio, Gonzalo H.
AU - Bizri, Abdul Rahman
AU - Andrade-Villanueva, Jaime F.
AU - Salman, Oday
AU - Cure-Cure, Carlos
AU - Rosado-Santander, Nelson R.
AU - Cornejo Giraldo, Mario P.
AU - González-Hernández, Luz A.
AU - Moghnieh, Rima
AU - Angeliki, Rapti
AU - Cruz Saldarriaga, María E.
AU - Pariona, Marcos
AU - Medina, Carola
AU - Dimitroulis, Ioannis
AU - Vlachopoulos, Charalambos
AU - Gutierrez, Corina
AU - Rodriguez-Mori, Juan E.
AU - Gomez-Laiton, Edgar
AU - Cotrina Pereyra, Rosa
AU - Ravelo Hernández, Jorge Luis
AU - Arbañil, Hugo
AU - Accini-Mendoza, José
AU - Pérez-Mayorga, Maritza
AU - Milionis, Charalampos
AU - Poulakou, Garyfallia
AU - Sánchez, Gregorio
AU - Valdivia-Vega, Renzo
AU - Villavicencio-Carranza, Mirko
AU - Ayala-García, Ricardo J.
AU - Castro-Callirgos, Carlos A.
AU - Alfaro Carrasco, Rosa M.
AU - Garrido Lecca Danos, Willy
AU - Sharkoski, Tiffany
AU - Greene, Katherine
AU - Pourmussa, Bianca
AU - Greczylo, Candy
AU - Ortega-Legaspi, Juan
AU - Jacoby, Douglas
AU - Chittams, Jesse
AU - Katsaounou, Paraskevi
AU - Alexiou, Zoi
AU - Sympardi, Styliani
AU - Sweitzer, Nancy K.
AU - Putt, Mary
AU - Cohen, Jordana B.
AU - Barrantes Alarcón, Ciro
AU - Mendoza Sanchez, Denisse Marylyn
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/12
Y1 - 2022/12
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85141517883&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141517883&partnerID=8YFLogxK
U2 - 10.1038/s42255-022-00698-3
DO - 10.1038/s42255-022-00698-3
M3 - Article
C2 - 36344766
AN - SCOPUS:85141517883
SN - 2522-5812
VL - 4
SP - 1847
EP - 1857
JO - Nature Metabolism
JF - Nature Metabolism
IS - 12
ER -