FEnofibRate as a Metabolic INtervention for COVID-19 (FERMIN)

FEnofibRate as a Metabolic INtervention for Coronavirus Disease 2019

The severe acute respiratory syndrome coronavirus 2 (SARS-CoC-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Aging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydrate metabolism are risk factors for death in COVID-19. Recent studies suggest that COVID-19 progression is dependent on metabolic mechanisms. Moreover, gene expression analyses in cultured human bronchial cells infected with SARS-CoV-2 and lung tissue from patients with COVID-19, indicated a marked shift in cellular metabolism, with 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 dyslipemias) 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. The aim of this trial is to assess the clinical impact of fenofibrate (145 mg/d of Tricor or dose-equivalent preparations for 10 days, with dose adjustment in chronic kidney disease ([CKD]) to improve clinical outcomes in patients with COVID-19.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Other: Fenofibrate/fenofibric acid; Other: Usual care; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 701
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A diagnosis of COVID-19, based on: (a) A compatible clinical presentation with a positive laboratory test for SARS-CoV-2, or (b) Considered by the primary team to be a Person Under Investigation undergoing testing for COVID-19 with a high clinical probability, in addition to compatible pulmonary infiltrates on chest x-ray (bilateral, intersticial or ground glass opacities) or chest CT.
• Able to provide informed consent.
• Fewer than 14 days since symptom onset.

Exclusion Criteria:

• Known pregnancy or breastfeeding
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 or undergoing dialysis (CKD stages 4-5).
• History of active liver disease, cholelithiasis, uncontrolled hypothyroidism, or rhabdomyolysis (suspected or confirmed). Patients with a history of hypothyroidism receiving a stable dose of thyroid replacement therapy for at least 6 weeks, with a documented normal TSH (primary hypothyroidism) or free thyroxine (secondary or tertiary hypothyroidism) level at least 6 weeks after the last dose change will be considered eligible for enrollment.
• Known hypersensitivity to fenofibrate or fenofibric acid.
• Ongoing treatment with fenofibrate, clofibrate, warfarin and other coumarin anticoagulants, glimepiride, cyclosporine, tacrolimus
• Use of statins other than simvastatin, pravastatin or atorvastatin ≤40 mg/d or rosuvastatin ≤20 mg/d
• Prisoners/incarcerated individuals
• Inability to read, write or no access to a smart phone, computer or tablet device
• Intubated patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenofibrate + Usual Care; The randomized intervention will be Fenofibrate, in combination with usual care. Dosing: 145 mg of Tricor or a dose-equivalent preparation	Other: Fenofibrate/fenofibric acid; The randomized intervention will be fenofibrate (Tricor) at a dose of 145 mg/d or dose-equivalent preparation of fenofibrate or fenofibric acid, for 10 days. In all cases, appropriate dose reductions will be implemented for patients with chronic kidney disease as per the approved preparation label. The intended duration of randomized treatment will be for 10 days.; Other: Usual care; All participants will otherwise receive usual medical care
Placebo Comparator: Placebo + Usual Care; The randomized intervention will a matching placebo, in combination with usual care.	Other: Usual care; All participants will otherwise receive usual medical care; Other: Placebo; The control intervention will be a placebo, for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Hierarchical Composite Endpoint	The primary endpoint of the trial is a global rank score that ranks patient outcomes according to 5 factors. The global rank score, or global severity score, is a nonparametric, hierarchically ranked outcome. The global rank score was generated by ranking all 701 participants on a scale of 1 to 701, from worst to best clinical outcomes. Participants were ranked by (1) time to death; (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) The inspired concentration of oxygen/percent oxygen saturation (FiO2/SpO2) ratio area under the curve; (4) For participants enrolled as outpatients who are subsequently hospitalized, the number of days out of the hospital during the 30 day-period following randomization; (5) For participants enrolled as outpatients who don't get hospitalized during the 30-day observation period, the modified Borg dyspnea scale	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days Alive, Out of the Intensive Care Unit, Free of Mechanical Ventilation/Extracorporeal Membrane Oxygenation, or Maximal Available Respiratory Support in the 30 Days Following Randomization	Number of days participants were alive, out of the intensive care unit, free of mechanical ventilation/extracorporeal membrane oxygenation, or maximal available respiratory support during the 30 days that followed randomization	Up to 30 days
Seven-category Ordinal Scale	A seven-category ordinal scale consisting of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and 7, death.	At 15 days
Secondary Hierarchical Composite Endpoint	The secondary global rank score, or global severity score, is a nonparametric, hierarchically ranked outcome. The global rank score was generated by ranking all 701 participants on a scale of 1 to 701, from worst to best clinical outcomes. Participants were ranked by (1) time to death; (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) The inspired concentration of oxygen/percent oxygen saturation (FiO2/SpO2) ratio area under the curve; (4) For participants enrolled as outpatients who are subsequently hospitalized, the number of days out of the hospital during the 30 day-period following randomization; (5) For participants enrolled as outpatients who don't get hospitalized during the 30-day observation period, a COVID-19 symptom scale rating fever, cough, dyspnea, muscle aches, sore throat, loss of smell or taste, headache, diarrhea, fatigue, nausea/vomiting, chest pain (each are rated from 0-10 then summed).	Up to 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Death	Death from any cause during the observation period	Up to 30 days
Number of Days Alive and Out of the Hospital During the 30 Days Following Randomization	Number of days that participants were alive and out of the hospital during the 30 days following randomization	Up to 30 days
Exploratory Hierarchical Composite Endpoint	The exploratory global rank score, or global severity score, is a nonparametric, hierarchically ranked outcome. The global rank score was generated by ranking all 701 participants on a scale of 1 to 701, from worst to best clinical outcomes. Participants were ranked by (1) time to death; (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) The inspired concentration of oxygen/percent oxygen saturation (FiO2/SpO2) ratio area under the curve; (4) The number of days out of the hospital during the 30 day-period following randomization.	Up to 30 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: University of Arizona; National Center for Advancing Translational Sciences (NCATS); G.Gennimatas General Hospital; Hospital Nacional Carlos Alberto Seguin Escobedo - EsSalud; Hospital Nacional Edgardo Rebagliati Martins; Universidad Católica de Santa María (National Sponsor in Perú); Hospital Nacional Adolfo Guevara Velasco, Peru; Hospital Nacional Alberto Sabogal Sologuren, Peru; Hospital Nacional Guillermo Almenara Irigoyen, Peru; Universidad de Santander, Bucaramanga, Colombia (National Sponsor in Colombia); Hospitales Civiles de Guadalajara, Mexico; Hospital 2 de Mayo. Lima, Peru; Hospital de la Fuerza Aérea del Perú. Lima, Peru; Hospital Militar Central "Coronel Luis Arias Schereiber"; Lima, Perú; Hospital Victor Lazarte Echegaray. Lima, Peru; Ioannina University General Hospital. Greece; AHEPA Thessaloniki University General Hospital. Greece; SOTIRIA Athens General University Hospital of Chest Diseases. Greece; THRIASIO Eleusis General Hospital. Greece; Alexandroupolis University General Hospital. Greece; Colombia Centro 1: BIOMELAB S.A.S. Barranquilla, Colombia; Fundación Oftalmológica de Santander. Santander, Colombia; IPS Centro Científico Asistencial. Barranquilla, Colombia; Fundación Cardiomet. Quindio, Colombia; Clínica de Marly. Bogotá, Colombia; Clinica Internacional. Lima, Peru

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibric acid; Fenofibrate
• Other Study ID Numbers: 843729

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not making it available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No