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Fenofibrate for Patients With COVID-19 Requiring Hospitalization (FENOC)

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ClinicalTrials.gov Identifier: NCT04661930
Recruitment Status : Recruiting
First Posted : December 10, 2020
Last Update Posted : December 10, 2020
Sponsor:
Collaborator:
Barzilai Medical Center
Information provided by (Responsible Party):
Yaakov Nahmias, Hebrew University of Jerusalem

Brief Summary:
This is an open-label run-in followed by a randomized, double-blind drug treatment study of COVID-19 infected patients requiring inpatient hospital admission.

Condition or disease Intervention/treatment Phase
Corona Virus Disease (COVID-19) Respiratory Distress Syndrome SARS-CoV-2 Infection Drug: TriCor® 145mg tablets Other: Usual Care Other: Placebo Phase 3

Detailed Description:
This is an open-label run-in followed by a randomized, double-blind drug treatment study of COVID-19 infected patients requiring inpatient hospital admission. Open-label patients will be matched at least 1:10 with observational retrospective Propensity score-matched (PSM) patients' medical files. The double-blinded step will be randomized 2:1 to daily Fenofibrate or placebo for 10 days or hospital discharge.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Controlled Trial of Fenofibrate for Patients With COVID-19 Requiring Hospitalization
Estimated Study Start Date : December 13, 2020
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : December 1, 2021


Arm Intervention/treatment
Experimental: Fenofibrate + Usual Care
Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.
Drug: TriCor® 145mg tablets
Fenofibrate; 145 mg daily (1/day); oral administration; 10 days
Other Name: Lipanthyl NT 145mg tablets

Other: Usual Care
All participants will otherwise receive usual medical care

Placebo Comparator: Placebo + Usual Care
Participants in this arm will receive a placebo treatment, in combination with usual care.
Other: Usual Care
All participants will otherwise receive usual medical care

Other: Placebo
Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration




Primary Outcome Measures :
  1. Difference in Plasma markers at 14 days [ Time Frame: 14 days ]

    Blood will be collected every third day for the duration of study participation.

    • D-dimer
    • Neutrophils
    • Lymphocytes
    • Platelets (PLT)
    • Glucose
    • Lactate
    • C-Reactive Protein (CRP)
    • Cardiac Troponin (TRO)
    • Ferritin

  2. 14-Day Mortality [ Time Frame: 14 days ]
    Outcome reported as the number of participants who have expired at 14 days post enrollment.

  3. Difference in Estimated P/F Ratio at 14 days [ Time Frame: 14 days ]
    Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available.

  4. Viral Clearance by Nasopharyngeal Swab [ Time Frame: 14 days ]
    Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. as number of viral genetic copies per mL.


Secondary Outcome Measures :
  1. Number of Abnormal Biomarker Days [ Time Frame: 14 days ]

    Outcome reported as the mean number of days participants in each arm had 2 or more abnormal plasma levels of:

    • D-dimer
    • Neutrophils
    • Lymphocytes
    • Platelets (PLT)
    • Glucose
    • Lactate
    • C-Reactive Protein (CRP)
    • Cardiac Troponin (TRO)
    • Ferritin

  2. Difference in Estimated PEEP adjusted P/F Ratio at 14 days [ Time Frame: 14 days ]
    Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio) and Expiratory Pressure.

  3. Difference in Oxygenation at 14 days [ Time Frame: 14 days ]
    PaO2 or SaO2 and FiO2. Partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry. FiO₂ is estimated from oxygen flow/delivery rates

  4. Daily Hypotensive Episodes [ Time Frame: 14 days ]
    Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL, new treatment with pressures, increase in 50% pressure or fluid rate) per participant in each arm.

  5. Hypotension Requiring Vasopressors [ Time Frame: 14 days ]
    Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

  6. Acute Kidney Injury [ Time Frame: 14 days ]
    Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

  7. Sequential Organ Failure Assessment (SOFA) Total Score [ Time Frame: 14 days ]
    The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely available software. Total scores range from 0-24, with higher scores indicating greater risk of mortality.

  8. Oxygen Saturation / Fractional Inhaled Oxygen (F/S) [ Time Frame: 14 days ]
    Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

  9. 28-Day Mortality [ Time Frame: 28 days ]
    Outcome reported as the number of participants who have expired at 28 days post enrollment.

  10. 90-Day Mortality [ Time Frame: 90 days ]
    Outcome reported as the number of participants who have expired at 90 days post enrollment.

  11. ICU Admission [ Time Frame: 14 days ]
    Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

  12. Number of Ventilator-Free Days [ Time Frame: 14 days ]
    Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

  13. Number of Therapeutic Oxygen-Free Days [ Time Frame: 14 days ]
    Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

  14. Number of Vasopressor-Free Days [ Time Frame: 14 days ]
    Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

  15. Length of ICU Stay [ Time Frame: 14 days ]
    Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

  16. Length of Hospital Stay [ Time Frame: 14 days ]
    Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

  17. Incidence of Respiratory Failure [ Time Frame: 14 days ]
    Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

  18. Change in PROMIS Dyspnea Functional Limitations [ Time Frame: 14 days ]
    The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

  19. Change in PROMIS Dyspnea Severity [ Time Frame: 14 days ]
    The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

  20. Disease Severity Rating [ Time Frame: 14 days ]
    Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

  21. Viral Load by Nasopharyngeal Swab [ Time Frame: 14 days ]
    Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

  22. Viral Load by Blood [ Time Frame: 14 days ]
    Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

  23. Viral Clearance by Blood [ Time Frame: 14 days ]
    Blood will be collected every third day for viral load assessment for the duration of study participation. clearance is measured as fold change in viral genetic copies per mL.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Presumptive positive laboratory test for SARS-CoV-2 based on local laboratory standard
  • Age greater than or equal to 18 years of age
  • Admission to the hospital with a respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2
  • Enrollment within 72 hours of presentation of hospital admission or within 72 hours of a positive test result, whichever is later

Exclusion Criteria:

  • Enrollment > 72 hours of admission order or positive test result, whichever is later
  • Admission to the hospital with a respiratory SOFA >=5 or Disease Severity Score >=5 (requiring noninvasive mechanical ventilation, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or all)
  • Known hypersensitivity to fenofibrate
  • For female subjects:

    1. Breastfeeding
    2. Undergoing fertility treatments
  • Patient-reported history or electronic medical record history of kidney disease, defined as:

    1. Any history of dialysis
    2. History of chronic kidney disease stage IV
    3. Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 at the time of enrollment
  • Acute pre-renal azotemia at the time of enrollment in the opinion of the investigator or bedside clinician
  • Most recent mean arterial blood pressure prior to enrollment <65 mmHg
  • Patient-reported history or electronic medical record history of severe liver disease, defined as:

    1. Cirrhosis
    2. History of hepatitis B or C
    3. Documented AST or ALT > 10 times the upper limit of normal measured within 24 hours prior to enrollment
  • Patient-reported history or electronic medical record history of gallbladder disease
  • Potassium >5.0 within 24 hours prior to enrollment unless a repeat value was <=5.0
  • Treatment with coumarin anticoagulants, immunosuppressants, or bile acid resins
  • Inability to obtain informed consent from participant or legally authorized representative
  • Enrollment in another blinded randomized clinical trial for COVID-19

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04661930


Contacts
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Contact: Yaakov Nahmias, PhD +972-2-5494640 ynahmias@cs.huji.ac.il
Contact: Avner Ehrlich +972-54-3181422 avner.ehrlich@mail.huji.ac.il

Locations
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Israel
Barzilai Medical Center Recruiting
Ashkelon, Israel, 7830604
Contact: Shlomo Maayan, MD         
Sponsors and Collaborators
Hebrew University of Jerusalem
Barzilai Medical Center
Investigators
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Principal Investigator: Shlomo Mayaan, MD Barzilai Medical Center
Study Director: Mahram Nassar, MD Barzilai Medical Center
Principal Investigator: Yaakov Nahmias, PhD Hebrew University of Jerusalem
Publications:
Ehrlich, A., Uhl, S., Ioannidis, K., Hofree, M., tenOever, B., and Nahmias, Y. (2020). The SARS-CoV-2 Transcriptional Metabolic Signature in Lung Epithelium. SSRN Electronic Journal.

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Responsible Party: Yaakov Nahmias, Controlled Trial of Fenofibrate for Patients With COVID-19 Requiring Hospitalization, Hebrew University of Jerusalem
ClinicalTrials.gov Identifier: NCT04661930    
Other Study ID Numbers: 0105-20-BRZ
First Posted: December 10, 2020    Key Record Dates
Last Update Posted: December 10, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Virus Diseases
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Fenofibrate
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents