Clinical trial NCT04661930: Fenofibrate for Patients With COVID-19 Requiring Hospitalization
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Corona Virus Disease (COVID-19)
Respiratory Distress Syndrome
SARS-CoV-2 Infection
Lead sponsor: Hebrew University of Jerusalem
Sponsor class: OTHER
Collaborators: name: Barzilai Medical Center
name: Rambam Health Care Campus
name: Nazareth Hospital
First posted: 2020-12-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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:

  1. Pregenant, determined by a human chorionic gonadotropin (HCG) rapid detection kit or a blood test
  2. Breastfeeding
  3. 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 (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

Primary outcomes:
measure: Number of Therapeutic Oxygen-Free Days
timeFrame: 14 days
measure: Length of Hospital Stay
timeFrame: 14 days
measure: Viral Clearance by Nasopharyngeal Swab
timeFrame: 14 days
measure: Difference in Estimated P/F Ratio at 14 days
timeFrame: 14 days
measure: Difference in Plasma Neutrophils at 14 days
timeFrame: 14 days
measure: Difference in Plasma Lymphocytes at 14 days
timeFrame: 14 days
measure: Difference in Plasma Monocytes at 14 days
timeFrame: 14 days
measure: Difference in Plasma C-Reactive Protein (CRP) at 14 days
timeFrame: 14 days
measure: Difference in Plasma IL-6 at 14 days
timeFrame: 14 days
measure: Difference in Plasma Procalcitonin (PCT) at 14 days
timeFrame: 14 days
measure: Difference in Plasma Ferritin at 14 days
timeFrame: 14 days
measure: Difference in NLR (Neutrophils to Lymphocytes Ratio) at 14 days
timeFrame: 14 days
Secondary outcomes:
measure: 14-Day Mortality
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Lactate
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Cardiac Troponin (TRO)
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Creatine Kinase (CK)
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Alanine Aminotransferase (ALT)
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Alkaline Phosphatase (ALP)
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - D-dimer
timeFrame: 14 days
measure: Difference in Organ Injury Plasma markers at 14 days - Platelets (PLT)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - D-dimer
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Neutrophils
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Lymphocytes
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Platelets (PLT)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Monocytes
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - C-Reactive Protein (CRP)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - IL-6
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Procalcitonin (PCT)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Lactate
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Cardiac Troponin (TRO)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Creatine Kinase (CK)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Alanine Aminotransferase (ALT)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Alkaline Phosphatase (ALP)
timeFrame: 14 days
measure: Number of Abnormal Biomarker Days - Ferritin
timeFrame: 14 days
measure: Difference in Oxygenation at 14 days
timeFrame: 14 days
measure: Difference in Estimated PEEP adjusted P/F Ratio at 14 days
timeFrame: 14 days
measure: Daily Hypotensive Episodes
timeFrame: 14 days
measure: Hypotension Requiring Vasopressors
timeFrame: 14 days
measure: Acute Kidney Injury
timeFrame: 14 days
measure: Sequential Organ Failure Assessment (SOFA) Total Score
timeFrame: 14 days
measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)
timeFrame: 14 days
measure: 28-Day Mortality
timeFrame: 28 days
measure: 90-Day Mortality
timeFrame: 90 days
measure: ICU Admission
timeFrame: 14 days
measure: Number of Ventilator-Free Days
timeFrame: 14 days
measure: Number of Vasopressor-Free Days
timeFrame: 14 days
measure: Length of ICU Stay
timeFrame: 14 days
measure: Incidence of Respiratory Failure
timeFrame: 14 days
measure: Change in PROMIS Dyspnea Functional Limitations
timeFrame: 14 days
measure: Change in PROMIS Dyspnea Severity
timeFrame: 14 days
measure: Disease Severity Rating
timeFrame: 14 days
measure: Viral Load by Nasopharyngeal Swab
timeFrame: 14 days
measure: Viral Load by Blood
timeFrame: 14 days
measure: Viral Clearance by Blood
timeFrame: 14 days
measure: Abnormal Biomarkers after recovery - D-dimer
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Neutrophils
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Lymphocytes
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Platelets (PLT)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Monocytes
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - C-Reactive Protein (CRP)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - IL-6
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Procalcitonin (PCT)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Lactate
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Cardiac Troponin (TRO)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Creatine Kinase (CK)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Alanine Aminotransferase (ALT)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Alkaline Phosphatase (ALP)
timeFrame: 1 day
measure: Abnormal Biomarkers after recovery - Ferritin
timeFrame: 1 day
measure: Abnormal Oxygenation after recovery
timeFrame: 1 day
measure: PROMIS Dyspnea Functional Limitations after recovery
timeFrame: 1 day
measure: PROMIS Dyspnea Severity after recovery
timeFrame: 1 day
Other outcomes:
measure: Significant post-acute incident diagnoses after recovery at 28-days
timeFrame: 1 day
measure: Significant post-acute incident diagnoses after recovery at 90-days
timeFrame: 1 day
measure: Significant post-acute incident diagnoses after recovery at 6-months
timeFrame: 1 day
Locations:
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Nazareth
country: Israel
facility: Nazareth Hospital EMMS
Study officials:
affiliation: Barzilai Medical Center
name: Shlomo Mayaan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barzilai Medical Center
name: Mahram Nassar, MD
role: STUDY_DIRECTOR
affiliation: Hebrew University of Jerusalem
name: Yaakov Nahmias, PhD
role: PRINCIPAL_INVESTIGATOR
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