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

Area of Science:

• Virology
• Pharmacology
• Clinical Medicine

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may be linked to peroxisome proliferator-activated receptor alpha (PPARα) inhibition.
• Fenofibrate, a PPARα activator, has demonstrated in vitro inhibition of SARS-CoV-2 replication.
• The potential therapeutic role of fenofibrate in human coronavirus disease 2019 (COVID-19) infection requires clinical investigation.

Purpose of the Study:

• To evaluate the efficacy of fenofibrate in treating COVID-19 patients.
• To assess the impact of fenofibrate on a composite severity score in COVID-19.

Main Methods:

• A double-blind, randomized trial was conducted involving 701 inpatients and outpatients with COVID-19 within 14 days of symptom onset.
• Participants received either 145 mg of oral fenofibrate nanocrystal formulation or a placebo daily for 10 days.
• The primary endpoint was a hierarchical severity score including mortality, mechanical ventilation, oxygenation, hospitalization, and symptom duration.

Main Results:

• Fenofibrate showed no significant effect on the primary severity endpoint compared to placebo (median rank 345 vs. 347, P=0.819).
• No differences were observed in secondary endpoints, including all-cause mortality, between the fenofibrate and placebo groups.
• Adverse events were lower in the fenofibrate group (13%) compared to placebo (17%), though gastrointestinal side effects were slightly more common with fenofibrate.

Conclusions:

• Fenofibrate did not demonstrate a significant clinical benefit for patients with COVID-19 in this randomized trial.
• The findings suggest that fenofibrate is not an effective treatment for improving outcomes in COVID-19 patients.
• Further research may explore alternative therapeutic strategies for COVID-19 management.