A Study of a 10-days Fenofibrate Treatment, or Until Discharge From Hospital, Among COVID-19 Infected Patients Requiring Hospitalization
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 55
- 试验地点
- 3
- 主要终点
- Difference in Plasma Monocytes at 14 days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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:
- •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
研究组 & 干预措施
Fenofibrate + Usual Care
Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.
干预措施: TriCor® 145mg tablets (Drug)
Fenofibrate + Usual Care
Participants in this arm will receive the study drug, Fenofibrate, in combination with usual care.
干预措施: Usual care (Other)
Placebo + Usual Care
Participants in this arm will receive placebo treatment, in combination with usual care.
干预措施: Placebo (Other)
Placebo + Usual Care
Participants in this arm will receive placebo treatment, in combination with usual care.
干预措施: Usual care (Other)
结局指标
主要结局
Difference in Plasma Monocytes at 14 days
时间窗: 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.
Viral Clearance by Nasopharyngeal Swab
时间窗: 14 days
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
时间窗: 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.
Number of Therapeutic Oxygen-Free Days
时间窗: 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.
Length of Hospital Stay
时间窗: 14 days
Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm
Difference in Plasma Neutrophils at 14 days
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Difference in Organ Injury Plasma markers at 14 days - D-dimer(14 days)
- 14-Day Mortality(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Platelets (PLT)(14 days)
- Number of Abnormal Biomarker Days - Monocytes(14 days)
- Number of Abnormal Biomarker Days - Lactate(14 days)
- Number of Abnormal Biomarker Days - Alkaline Phosphatase (ALP)(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Lactate(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Cardiac Troponin (TRO)(14 days)
- Number of Abnormal Biomarker Days - Lymphocytes(14 days)
- Number of Abnormal Biomarker Days - C-Reactive Protein (CRP)(14 days)
- Number of Abnormal Biomarker Days - Procalcitonin (PCT)(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Creatine Kinase (CK)(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Alanine Aminotransferase (ALT)(14 days)
- Difference in Organ Injury Plasma markers at 14 days - Alkaline Phosphatase (ALP)(14 days)
- Hypotension Requiring Vasopressors(14 days)
- Number of Abnormal Biomarker Days - D-dimer(14 days)
- Number of Abnormal Biomarker Days - Neutrophils(14 days)
- Number of Abnormal Biomarker Days - Platelets (PLT)(14 days)
- Number of Abnormal Biomarker Days - IL-6(14 days)
- Number of Abnormal Biomarker Days - Cardiac Troponin (TRO)(14 days)
- Number of Abnormal Biomarker Days - Creatine Kinase (CK)(14 days)
- Number of Abnormal Biomarker Days - Alanine Aminotransferase (ALT)(14 days)
- Number of Abnormal Biomarker Days - Ferritin(14 days)
- Difference in Oxygenation at 14 days(14 days)
- Viral Load by Blood(14 days)
- Difference in Estimated PEEP adjusted P/F Ratio at 14 days(14 days)
- Daily Hypotensive Episodes(14 days)
- Acute Kidney Injury(14 days)
- Change in PROMIS Dyspnea Severity(14 days)
- Disease Severity Rating(14 days)
- Viral Load by Nasopharyngeal Swab(14 days)
- Sequential Organ Failure Assessment (SOFA) Total Score(14 days)
- Oxygen Saturation / Fractional Inhaled Oxygen (F/S)(14 days)
- 90-Day Mortality(90 days)
- Number of Vasopressor-Free Days(14 days)
- Abnormal Biomarkers after recovery - D-dimer(1 day)
- Abnormal Biomarkers after recovery - Neutrophils(1 day)
- Abnormal Biomarkers after recovery - Lymphocytes(1 day)
- Abnormal Biomarkers after recovery - C-Reactive Protein (CRP)(1 day)
- Abnormal Biomarkers after recovery - Lactate(1 day)
- Abnormal Biomarkers after recovery - Creatine Kinase (CK)(1 day)
- Abnormal Biomarkers after recovery - Ferritin(1 day)
- PROMIS Dyspnea Functional Limitations after recovery(1 day)
- 28-Day Mortality(28 days)
- ICU Admission(14 days)
- Number of Ventilator-Free Days(14 days)
- Incidence of Respiratory Failure(14 days)
- Length of ICU Stay(14 days)
- Change in PROMIS Dyspnea Functional Limitations(14 days)
- Viral Clearance by Blood(14 days)
- Abnormal Biomarkers after recovery - Platelets (PLT)(1 day)
- Abnormal Biomarkers after recovery - Monocytes(1 day)
- Abnormal Biomarkers after recovery - IL-6(1 day)
- Abnormal Biomarkers after recovery - Cardiac Troponin (TRO)(1 day)
- Abnormal Oxygenation after recovery(1 day)
- PROMIS Dyspnea Severity after recovery(1 day)
- Abnormal Biomarkers after recovery - Procalcitonin (PCT)(1 day)
- Abnormal Biomarkers after recovery - Alkaline Phosphatase (ALP)(1 day)
- Abnormal Biomarkers after recovery - Alanine Aminotransferase (ALT)(1 day)
研究者
Yaakov Nahmias
Director of the Grass Center for Bioengineering
Hebrew University of Jerusalem