FEnofibRate as a Metabolic INtervention for COVID-19

NCT04517396 | Completed Phase 2 Results DMC

• 1 other identifier: 843729
• Study Type: interventional
• Target: 701
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

  Up to 30 days

• Seven-category Ordinal Scale

  At 15 days

• Secondary Hierarchical Composite Endpoint

  Up to 30 days

Other Outcomes (3)

• All-Cause Death

  Up to 30 days

• Number of Days Alive and Out of the Hospital During the 30 Days Following Randomization

  Up to 30 days

• Exploratory Hierarchical Composite Endpoint

  Up to 30 days

Study Arms (2)

Fenofibrate + Usual Care

EXPERIMENTAL

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; Other: Usual care

Placebo + Usual Care

PLACEBO COMPARATOR

The randomized intervention will a matching placebo, in combination with usual care.

Other: Placebo; Other: Usual care

Interventions

Fenofibrate/fenofibric acid OTHER

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.

Fenofibrate + Usual Care

Placebo OTHER

The control intervention will be a placebo, for 10 days.

Placebo + Usual Care

Usual care OTHER

All participants will otherwise receive usual medical care

Fenofibrate + Usual Care; Placebo + Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• University of Arizona: collaborator
• Universidad Católica de Santa María: collaborator
• Hospital Nacional Adolfo Guevara Velasco: collaborator
• Hospital Nacional Edgardo Rebagliati Martins: collaborator
• Hospital Nacional Alberto Sabogal Sologuren: collaborator
• Hospital Nacional Guillermo Almenara Irigoyen: collaborator
• Hospital Nacional Carlos Alberto Seguin Escobedo - EsSalud: collaborator
• Universidad de Santander: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Hospital Civil de Guadalajara: collaborator
• Hospital Nacional Dos De Mayo: collaborator
• Hospital Central Fuerza Aérea del Perú: collaborator
• Hospital Militar Central.Coronel Luis Arias Schereiber: collaborator
• Hospital Victor Lazarte Echegaray: collaborator
• University Hospital, Ioannina: collaborator
• AHEPA University Hospital: collaborator
• Sotiria Thoracic Diseases Hospital of Athens: collaborator
• Thriasio General Hospital of Elefsina: collaborator
• University Hospital, Alexandroupolis: collaborator
• G.Gennimatas General Hospital: collaborator
• Biomelab S.A.S.: collaborator
• Fundación Oftalmológica de Santander. Santander, Colombia: collaborator
• IPS Centro Científico Asistencial. Barranquilla, Colombia: collaborator
• Fundación Cardiomet. Quindio, Colombia: collaborator
• ClÍnica de Marly: collaborator
• Clínica Internacional: collaborator

Study Sites (1)

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

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• Chirinos J, Lopez-Jaramillo P, Giamarellos-Bourboulis E, Davila-Del-Carpio G, Bizri A, Andrade-Villanueva J, Salman O, Cure-Cure C, Rosado-Santander N, Giraldo MC, Gonzalez-Hernandez L, Moghnieh R, Angeliki R, Saldarriaga MC, Pariona M, Medina C, Dimitroulis I, Vlachopoulos C, Gutierrez C, Rodriguez-Mori J, Gomez-Laiton E, Pereyra R, Hernandez JR, Arbanil H, Accini-Mendoza J, Perez-Mayorga M, Milionis H, Poulakou G, Sanchez G, Valdivia-Vega R, Villavicencio-Carranza M, Ayala-Garcia R, Castro-Callirgos C, Carrasco RA, Danos WL, Sharkoski T, Greene K, Pourmussa B, Greczylo C, Chittams J, Katsaounou P, Alexiou Z, Sympardi S, Sweitzer N, Putt M, Cohen J. A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019. Res Sq [Preprint]. 2022 Aug 10:rs.3.rs-1933913. doi: 10.21203/rs.3.rs-1933913/v1.

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MeSH Terms

Conditions

COVID-19

Interventions

Fenofibrate; fenofibric acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones

Limitations and Caveats

The study enrolled participants over an 18-month period where several different SARS-CoV-2 variants dominated, and national interventions and vaccine availability varied at different timepoints. Additionally, components of the hierarchical endpoints may be subjective.

Results Point of Contact

• Title: Katherine Greene
• Organization: University of Pennsylvania

katherine.greene@pennmedicine.upenn.edu

215-662-7580

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine at the Hospital of the University of Pennsylvania

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 18, 2020
• Study Start: August 18, 2020
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: March 24, 2023
• Results First Posted: February 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)