Efficacy of Fenofibrate for COVID-19: A phase II randomized controlled trial

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PROJECT SUMMARY Aging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydrate metabolism are risk factors for death in Coronavirus disease 2019 (COVID-19). Recent studies suggest that COVID-19 infection of human lung primary bronchial epithelial cells is dependent on metabolic mechanisms including a marked shift in cellular metabolism that leads to excessive intracellular lipid generation. In this cell culture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple other regulatory agencies around the world to treat dyslipidemias) at concentrations that can be achieved clinically, markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may be beneficial in the setting of COVID-19. We propose an international multicenter randomized placebo-controlled trial to assess the impact of fenofibrate on outcomes in patients with COVID-19. We will administer fenofibrate (145 mg/d of Tricor or dose- equivalent preparations for 10 days, with dose adjustment in chronic kidney disease [CKD]) will be tested. Our primary endpoint will be a global score that ranks patient outcomes according to 5 clinically important patient- centric outcomes. Out hierarchical endpoint achieves high statistical power and thus maximized the likelihood of productive phase II trials that can readily identify potential therapies for advance into phase III trials. We will assess various secondary and exploratory endpoints. Finally, we aim to consolidate an international network that can rapidly execute phase II trials in COVID-19, leveraging established collaborations with COVID-19 clinical researchers in Latin America. This network can readily execute this trial and support other NIH-funded trials. Our proposal has the potential to advance a novel therapy (fenofibrate), a widely available, generic and inexpensive drug with a proven track record of safety. If fenofibrate is effective for COVID-19, our trial could have a major public health impact on the COVID-19 pandemic.