Back to resultsFenofibrate for Patients With COVID-19 Requiring Hospitalization (FENOC)
Primary Purpose
Corona Virus Disease (COVID-19), Respiratory Distress Syndrome, SARS-CoV-2 Infection
Status
Recruiting
Phase
Phase 3
Locations
Israel
Study Type
Interventional
Intervention
TriCor® 145mg tablets
Placebo
Usual care
Sponsored by
About this trial
This is an interventional treatment trial for Corona Virus Disease (COVID-19)
Eligibility 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
Severe COVID-19, defined by:
- A disease severity score of 3 (Hospitalized, on non-invasive ventilation or high flow oxygen devices) to 4 (Hospitalized, requiring supplemental oxygen).
AND o A respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2, a blood oxygen saturation of 93% or less on room air, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) of less than 300 mm Hg, respiratory rate >30 breaths/min, or lung infiltrates >50% on chest CT
• 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 , Critical COVID-19, or Disease Severity Score >5 (requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or all)
- Known hypersensitivity to fenofibrate
For female subjects:
- Pregenant, determined by a human chorionic gonadotropin (HCG) rapid detection kit or a blood test
- Breastfeeding
- Undergoing fertility treatments
Patient-reported history or electronic medical record history of kidney disease, defined as:
- Any history of dialysis
- History of chronic kidney disease stage IV
- 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:
- Cirrhosis
- History of hepatitis B or C
- 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 (e.g., Warfarin), immunosuppressants (e.g. cisplatin), bile acid resins, or sulfonylurea.
- Inability to obtain informed consent from participant or legally authorized representative
- Enrollment in another blinded randomized clinical trial for COVID
Sites / Locations
- Barzilai Medical CenterRecruiting
- Rambam Health Care CampusRecruiting
- Nazareth Hospital EMMSRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
No Intervention
Arm Label
Fenofibrate + Usual Care
Placebo + Usual Care
Usual Care (Observetional)
Arm Description
Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.
Participants in this arm will receive placebo treatment, in combination with usual care.
Participants in this arm will receive the usual care and be compared by their medical records and laboratory results
Outcomes
Primary Outcome Measures
Number of Therapeutic Oxygen-Free 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.
Length of Hospital Stay
Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm
Viral Clearance by Nasopharyngeal Swab
Nasopharyngeal swabs will be collected every second day for the duration of study participation. Viral clearance is measured as fold change in viral genetic copies per mL
Difference in Estimated P/F Ratio at 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.
Difference in Plasma Neutrophils at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma Lymphocytes at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma Monocytes at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma C-Reactive Protein (CRP) at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma IL-6 at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma Procalcitonin (PCT) at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Plasma Ferritin at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in NLR (Neutrophils to Lymphocytes Ratio) at 14 days
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Secondary Outcome Measures
14-Day Mortality
Outcome reported as the number of participants who have expired at 14 days post enrollment.
Difference in Organ Injury Plasma markers at 14 days - Lactate
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - Cardiac Troponin (TRO)
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - Creatine Kinase (CK)
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - Alanine Aminotransferase (ALT)
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - Alkaline Phosphatase (ALP)
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - D-dimer
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Difference in Organ Injury Plasma markers at 14 days - Platelets (PLT)
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Number of Abnormal Biomarker Days - D-dimer
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Neutrophils
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Lymphocytes
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Platelets (PLT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Monocytes
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - C-Reactive Protein (CRP)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - IL-6
Outcome reported as the mean number of days participants in each arm had 2 or more abnormal plasma levels.
Number of Abnormal Biomarker Days - Procalcitonin (PCT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Lactate
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Cardiac Troponin (TRO)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Creatine Kinase (CK)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Alanine Aminotransferase (ALT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Alkaline Phosphatase (ALP)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Number of Abnormal Biomarker Days - Ferritin
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Difference in Oxygenation at 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
Difference in Estimated PEEP adjusted P/F Ratio at 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.
Daily Hypotensive Episodes
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.
Hypotension Requiring Vasopressors
Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Acute Kidney Injury
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.
Sequential Organ Failure Assessment (SOFA) Total Score
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.
Oxygen Saturation / Fractional Inhaled Oxygen (F/S)
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.
28-Day Mortality
Outcome reported as the number of participants who have expired at 28 days post enrollment.
90-Day Mortality
Outcome reported as the number of participants who have expired at 90 days post enrollment.
ICU Admission
Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Number of Ventilator-Free Days
Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Number of Vasopressor-Free Days
Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Length of ICU Stay
Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Incidence of Respiratory Failure
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.
Change in PROMIS Dyspnea Functional Limitations
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.
Change in PROMIS Dyspnea Severity
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.
Disease Severity Rating
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.
Viral Load by Nasopharyngeal Swab
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.
Viral Load by Blood
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.
Viral Clearance by Blood
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.
Abnormal Biomarkers after recovery - D-dimer
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Neutrophils
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Lymphocytes
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Platelets (PLT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Monocytes
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - C-Reactive Protein (CRP)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - IL-6
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Procalcitonin (PCT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Lactate
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Cardiac Troponin (TRO)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Creatine Kinase (CK)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Alanine Aminotransferase (ALT)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Alkaline Phosphatase (ALP)
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Biomarkers after recovery - Ferritin
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Abnormal Oxygenation after recovery
Outcome reported as the mean number of participants in each arm had abnormal PaO2 or SaO2 and FiO2 levels at the end of quarantine period. Partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry. FiO₂ is estimated from oxygen flow/delivery rates
PROMIS Dyspnea Functional Limitations after recovery
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. Measured at the end of quarantine period.
PROMIS Dyspnea Severity after recovery
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. Measured at the end of quarantine period.
Full Information
NCT ID
NCT04661930
First Posted
December 9, 2020
Last Updated
April 17, 2022
Sponsor
Yaakov Nahmias
Collaborators
Barzilai Medical Center, Rambam Health Care Campus, Nazareth Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04661930
Brief Title
Fenofibrate for Patients With COVID-19 Requiring Hospitalization
Acronym
FENOC
Official Title
A Study of a 10-days Fenofibrate Treatment, or Until Discharge From Hospital, Among COVID-19 Infected Patients Requiring Hospitalization
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
May 1, 2022 (Anticipated)
Study Completion Date
July 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yaakov Nahmias
Collaborators
Barzilai Medical Center, Rambam Health Care Campus, Nazareth Hospital
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Disease (COVID-19), Respiratory Distress Syndrome, SARS-CoV-2 Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
An interventional single-arm non-randomized pilot study in 15 patients, followed by an Interventional double-blinded randomized quadruple masked study in 40 patients.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
55 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fenofibrate + Usual Care
Arm Type
Experimental
Arm Description
Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.
Arm Title
Placebo + Usual Care
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive placebo treatment, in combination with usual care.
Arm Title
Usual Care (Observetional)
Arm Type
No Intervention
Arm Description
Participants in this arm will receive the usual care and be compared by their medical records and laboratory results
Intervention Type
Drug
Intervention Name(s)
TriCor® 145mg tablets
Other Intervention Name(s)
Lipanthyl NT 145mg tablets
Intervention Description
Fenofibrate; 145 mg daily (1/day); oral administration; 10 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo (microcrystalline methylcellulose, gelatin capsule); oral administration
Intervention Type
Other
Intervention Name(s)
Usual care
Intervention Description
All participants will otherwise receive usual medical care
Primary Outcome Measure Information:
Title
Number of Therapeutic Oxygen-Free Days
Description
Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Time Frame
14 days
Title
Length of Hospital Stay
Description
Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm
Time Frame
14 days
Title
Viral Clearance by Nasopharyngeal Swab
Description
Nasopharyngeal swabs will be collected every second day for the duration of study participation. Viral clearance is measured as fold change in viral genetic copies per mL
Time Frame
14 days
Title
Difference in Estimated P/F Ratio at 14 days
Description
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.
Time Frame
14 days
Title
Difference in Plasma Neutrophils at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma Lymphocytes at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma Monocytes at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma C-Reactive Protein (CRP) at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma IL-6 at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma Procalcitonin (PCT) at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Plasma Ferritin at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in NLR (Neutrophils to Lymphocytes Ratio) at 14 days
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
14-Day Mortality
Description
Outcome reported as the number of participants who have expired at 14 days post enrollment.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Lactate
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Cardiac Troponin (TRO)
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Creatine Kinase (CK)
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Alanine Aminotransferase (ALT)
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Alkaline Phosphatase (ALP)
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - D-dimer
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Difference in Organ Injury Plasma markers at 14 days - Platelets (PLT)
Description
Blood will be collected every second day for the duration of study participation. Difference will be calculated based on the first measurement after admission to the study.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - D-dimer
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Neutrophils
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Lymphocytes
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Platelets (PLT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Monocytes
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - C-Reactive Protein (CRP)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - IL-6
Description
Outcome reported as the mean number of days participants in each arm had 2 or more abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Procalcitonin (PCT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Lactate
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Cardiac Troponin (TRO)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Creatine Kinase (CK)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Alanine Aminotransferase (ALT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Alkaline Phosphatase (ALP)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Number of Abnormal Biomarker Days - Ferritin
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
14 days
Title
Difference in Oxygenation at 14 days
Description
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
Time Frame
14 days
Title
Difference in Estimated PEEP adjusted P/F Ratio at 14 days
Description
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.
Time Frame
14 days
Title
Daily Hypotensive Episodes
Description
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.
Time Frame
14 days
Title
Hypotension Requiring Vasopressors
Description
Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Time Frame
14 days
Title
Acute Kidney Injury
Description
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.
Time Frame
14 days
Title
Sequential Organ Failure Assessment (SOFA) Total Score
Description
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.
Time Frame
14 days
Title
Oxygen Saturation / Fractional Inhaled Oxygen (F/S)
Description
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.
Time Frame
14 days
Title
28-Day Mortality
Description
Outcome reported as the number of participants who have expired at 28 days post enrollment.
Time Frame
28 days
Title
90-Day Mortality
Description
Outcome reported as the number of participants who have expired at 90 days post enrollment.
Time Frame
90 days
Title
ICU Admission
Description
Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Time Frame
14 days
Title
Number of Ventilator-Free Days
Description
Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Time Frame
14 days
Title
Number of Vasopressor-Free Days
Description
Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Time Frame
14 days
Title
Length of ICU Stay
Description
Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Time Frame
14 days
Title
Incidence of Respiratory Failure
Description
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.
Time Frame
14 days
Title
Change in PROMIS Dyspnea Functional Limitations
Description
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.
Time Frame
14 days
Title
Change in PROMIS Dyspnea Severity
Description
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.
Time Frame
14 days
Title
Disease Severity Rating
Description
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.
Time Frame
14 days
Title
Viral Load by Nasopharyngeal Swab
Description
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.
Time Frame
14 days
Title
Viral Load by Blood
Description
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.
Time Frame
14 days
Title
Viral Clearance by Blood
Description
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.
Time Frame
14 days
Title
Abnormal Biomarkers after recovery - D-dimer
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Neutrophils
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Lymphocytes
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Platelets (PLT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Monocytes
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - C-Reactive Protein (CRP)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - IL-6
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Procalcitonin (PCT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Lactate
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Cardiac Troponin (TRO)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Creatine Kinase (CK)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Alanine Aminotransferase (ALT)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Alkaline Phosphatase (ALP)
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Biomarkers after recovery - Ferritin
Description
Outcome reported as the mean number of days participants in each arm had abnormal plasma levels.
Time Frame
1 day
Title
Abnormal Oxygenation after recovery
Description
Outcome reported as the mean number of participants in each arm had abnormal PaO2 or SaO2 and FiO2 levels at the end of quarantine period. Partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry. FiO₂ is estimated from oxygen flow/delivery rates
Time Frame
1 day
Title
PROMIS Dyspnea Functional Limitations after recovery
Description
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. Measured at the end of quarantine period.
Time Frame
1 day
Title
PROMIS Dyspnea Severity after recovery
Description
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. Measured at the end of quarantine period.
Time Frame
1 day
Other Pre-specified Outcome Measures:
Title
Significant post-acute incident diagnoses after recovery at 28-days
Description
Incident rate per 1000 at 28-days in hospitalized COVID-19 is ascertained from hospital admission until 28-days or end of follow-up.
Time Frame
1 day
Title
Significant post-acute incident diagnoses after recovery at 90-days
Description
Incident rate per 1000 at 90-days in hospitalized COVID-19 is ascertained from hospital admission until 90-days or end of follow-up.
Time Frame
1 day
Title
Significant post-acute incident diagnoses after recovery at 6-months
Description
Incident rate per 1000 at 6-months in hospitalized COVID-19 is ascertained from hospital admission until 6-months or end of follow-up.
Time Frame
1 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Severe COVID-19, defined by:
A disease severity score of 3 (Hospitalized, on non-invasive ventilation or high flow oxygen devices) to 4 (Hospitalized, requiring supplemental oxygen).
AND o A respiratory SOFA >=1 and increased oxygen requirement compared to baseline among those on home O2, a blood oxygen saturation of 93% or less on room air, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) of less than 300 mm Hg, respiratory rate >30 breaths/min, or lung infiltrates >50% on chest CT
• 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 , Critical COVID-19, or Disease Severity Score >5 (requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or all)
Known hypersensitivity to fenofibrate
For female subjects:
Pregenant, determined by a human chorionic gonadotropin (HCG) rapid detection kit or a blood test
Breastfeeding
Undergoing fertility treatments
Patient-reported history or electronic medical record history of kidney disease, defined as:
Any history of dialysis
History of chronic kidney disease stage IV
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:
Cirrhosis
History of hepatitis B or C
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 (e.g., Warfarin), immunosuppressants (e.g. cisplatin), bile acid resins, or sulfonylurea.
Inability to obtain informed consent from participant or legally authorized representative
Enrollment in another blinded randomized clinical trial for COVID
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yaakov Nahmias, PhD
Phone
+972-2-5494640
Email
ynahmias@cs.huji.ac.il
First Name & Middle Initial & Last Name or Official Title & Degree
Avner Ehrlich
Phone
+972-54-3181422
Email
avner.ehrlich@mail.huji.ac.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shlomo Mayaan, MD
Organizational Affiliation
Barzilai Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mahram Nassar, MD
Organizational Affiliation
Barzilai Medical Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Yaakov Nahmias, PhD
Organizational Affiliation
Hebrew University of Jerusalem
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barzilai Medical Center
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shlomo Maayan, MD
Facility Name
Rambam Health Care Campus
City
Haifa
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shadi Hamoud, Prof. MD.
Phone
04-7773097
Email
s_hamoud@rmc.gov.il
First Name & Middle Initial & Last Name & Degree
Shadi Hamoud, Prof. MD.
Facility Name
Nazareth Hospital EMMS
City
Nazareth
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amir Alimi, MD
First Name & Middle Initial & Last Name & Degree
Amir Alimi, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32242089
Citation
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Results Reference
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Citation
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.
Results Reference
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PubMed Identifier
20580052
Citation
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Results Reference
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PubMed Identifier
28831119
Citation
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Results Reference
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PubMed Identifier
30654597
Citation
Yan B, Chu H, Yang D, Sze KH, Lai PM, Yuan S, Shuai H, Wang Y, Kao RY, Chan JF, Yuen KY. Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication. Viruses. 2019 Jan 16;11(1):73. doi: 10.3390/v11010073.
Results Reference
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PubMed Identifier
19333547
Citation
Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010 Sep;47(3):193-9. doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31.
Results Reference
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PubMed Identifier
30631056
Citation
Yuan S, Chu H, Chan JF, Ye ZW, Wen L, Yan B, Lai PM, Tee KM, Huang J, Chen D, Li C, Zhao X, Yang D, Chiu MC, Yip C, Poon VK, Chan CC, Sze KH, Zhou J, Chan IH, Kok KH, To KK, Kao RY, Lau JY, Jin DY, Perlman S, Yuen KY. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Nat Commun. 2019 Jan 10;10(1):120. doi: 10.1038/s41467-018-08015-x.
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PubMed Identifier
32369736
Citation
Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Zhang P, Song X, Chen X, Xiang M, Zhang C, Bai L, Xiang D, Chen MM, Liu Y, Yan Y, Liu M, Mao W, Zou J, Liu L, Chen G, Luo P, Xiao B, Zhang C, Zhang Z, Lu Z, Wang J, Lu H, Xia X, Wang D, Liao X, Peng G, Ye P, Yang J, Yuan Y, Huang X, Guo J, Zhang BH, Li H. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020 Jun 2;31(6):1068-1077.e3. doi: 10.1016/j.cmet.2020.04.021. Epub 2020 May 1.
Results Reference
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Fenofibrate for Patients With COVID-19 Requiring Hospitalization
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