FEnofibRate as a Metabolic INtervention for COVID-19
Condition: Covid19
MeSH terms: COVID-19
Intervention: Fenofibrate/fenofibric acid; Placebo; Usual care
Intervention description: 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.; The control intervention will be a placebo, for 10 days.; All participants will otherwise receive usual medical care
Intervention MeSH terms: Fenofibrate; Fenofibric acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 701.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.