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COVID-FISETIN: Pilot in Covid-19 of Fisetin to Alleviate Dysfunction and Inflammation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04476953
Recruitment Status : Enrolling by invitation
First Posted : July 20, 2020
Last Update Posted : August 13, 2020
Sponsor:
Information provided by (Responsible Party):
James L. Kirkland, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE July 15, 2020
First Posted Date  ICMJE July 20, 2020
Last Update Posted Date August 13, 2020
Actual Study Start Date  ICMJE August 3, 2020
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2020)
  • Serious Adverse Events [ Time Frame: 6 months ]
    Number of participants to experience serious adverse events and hypersensitivity reactions.
  • Change in oxygenation status [ Time Frame: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6 ]
    change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2020)
COVID-19 Severity Category [ Time Frame: 6 months ]
Number of participants to progress to severe or critical classification measure by the WHO/ NIH Baseline Severity Classification criteria descriptions of SARS-CoV-2 infection without symptoms, Mild COVID-19 (CoV), Moderate CoV, Severe CoV and Critical CoV
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COVID-FISETIN: Pilot in Covid-19 of Fisetin to Alleviate Dysfunction and Inflammation
Official Title  ICMJE COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in Covid-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults
Brief Summary The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.
Detailed Description To determine if Fisetin treatment can prevent deterioration of oxygenation status as measured by S/F ratio: SpO2/ FiO2, as well as prevent deterioration in physical function (frailty) and hyper-inflammation, other measures of oxygenation status (progression to supplemental oxygen requirement, assisted breathing/ ventilation), and progression from mild/ moderate to severe/ critical proven COVID-19 (CoV) infection (WHO/NIH Baseline Severity Classification) in non-ICU hospitalized patients and to evaluate the safety and tolerability of Fisetin in this patient population.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Placebo
    Placebo looks exactly like the study drug, but it contains no active ingredient.
  • Drug: Fisetin
    ~20 mg/kg/day oral, NG or D tube course for 2 consecutive days
    Other Name: 3,3',4',7-tetrahydroxyflavone
Study Arms  ICMJE
  • Experimental: Treatment Group
    Subjects will receive treatment drug Fisetin
    Intervention: Drug: Fisetin
  • Placebo Comparator: Placebo Group
    Subjects will receive placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: July 16, 2020)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria - Patients must meet all of the following inclusion criteria to be enrolled in this study.

  1. Men or women 60 years of age or older

    OR

    Age 18 - 59 years WITH at least one of the following comorbidities:

    • BMI greater than or equal to 35
    • Diabetes
    • Asthma/ Chronic Obstructive Pulmonary Disease (COPD)
    • Previous Myocardial Infarction
    • Previous Stroke/ Cerebrovascular Accident (CVA)
    • Hypertension/ Atherosclerosis/ Peripheral Vascular Disease
    • Smoking and/or vaping
    • Other conditions associated with senescent cell accumulation (i.e. previous chemotherapy or radiation)
  2. SpO2 greater than or equal to 85% on room air within previous 72 hours AND 2 L of oxygen or less by nasal cannula (or on room air) at time of enrollment.
  3. Willing and able to provide written informed consent or have a legally authorized representative (LAR) who will provide informed consent.
  4. SARS-CoV-2 infection confirmed by PCR test at Mayo Clinic's Central Laboratory within 72 hours before randomization.

Exclusion Criteria - Patients who meet any of the following exclusion criteria are not to be enrolled in this study.

General Exclusion Criteria

  1. Presence of any condition that the Investigator or the subject's attending physician believes would put the subject at risk or would preclude the patient from successfully completing the trial.
  2. Mechanically-ventilated (including V-V ECMO or V-A ECMO).
  3. Severe or critical CoV (WHO/ NIH Categorization; Table 3) at time of randomization.
  4. Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative pregnancy test within 72 hours prior to randomization.
  5. WCBP who are unwilling to abstain from sex or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration. (Section 5.10)
  6. Men who are unwilling to abstain from sex with WCBP or use an adequate method of contraception from the time of the first IP administration through 48 hours after the last IP administration. (Section 5.10)

    Laboratory Exclusion Criteria

  7. Total bilirubin >3X upper limit of normal or as per clinical judgment.
  8. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) >4x the upper limits of normal or as per clinical judgment.
  9. Hemoglobin <7 g/dL; white blood cell count ≤ 2,000/mm3 (< or = 2.0 x 109/L) or > or = 20,000/mm3 (> or = 20 x 109/L); platelet count < or = 60,000/µL (< or = 60 x 109/L); absolute neutrophil count < or = 1 x 109/L; lymphocyte count <0.5 x 109/L at screening or as per clinical judgment.
  10. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine, immunological, or hepatic disorder.
  11. eGFR <25 ml/ min/ 1.73 m2 or as per clinical judgment.
  12. Plasma glucose >300 or as per clinical judgment.
  13. Cystatin C >3x upper limit of normal or as per clinical judgment.

    Clinical History Exclusion Criteria

  14. Human immunodeficiency virus infection.
  15. Known active hepatitis B or C infection.
  16. Invasive fungal infection.
  17. Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites.
  18. New/active invasive cancer except non-melanoma skin cancers.

    Medication Exclusion Criteria (See Appendices 1-3 for additional information)

  19. Known hypersensitivity or allergy to Fisetin.
  20. Patients currently using medications which utilize CYP450 2C9 for metabolism. These medications include: Fosphenytoin, Phenytoin, Warfarin, Glimepiride, Diclofenac, Bosentan, and Glyburide. Patients taking Losartan may participate if Losartan can be held until study Day 3 and the patient is otherwise eligible.
  21. Patients currently using medications which utilize CYP2C9, CYP2C19, CYP1A2, OATP1B1. These medications include: Olanzapine, Clozapine, Theophylline, Tizanidine, Warfarin, Rameltoen, Tacrine, Duloxetine, Mexiletine, Riluzole, and Atomoxetine. Patients taking Colchicine may participate if Colchicine can be reduced by half until study Day 3 and the patient is otherwise eligible. Patients taking Venlafaxine may participate if Venlafaxine can be held until study Day 3 and the patient is otherwise eligible.
  22. Patients currently using medications which are strong inhibitors of CYP3A4. These medications include: Atazanavir, Ceritinib, Clarithromycin, Darunavir, Idelalisib, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mefipristone, Nefazodone, Nelfinavir, Ombitasivir-paritaprevir-ritonivir, Ombitasivir-paritaprevir-ritonivir-plus dasabuvir, Posaconazole, Saquinavir, Telithromycin, Tucatinib, and Voriconazole.
  23. Patients currently using antifungals. If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are subtherapeutic or therapeutic.
  24. Patients currently using any of the following medications (unless willing to discontinue the medication during the study):

    • Cardiac: digoxin, flecainide, amiodarone
    • Psychiatric: lithium, thioridazine
    • Neurologic: carbamazepine, phenobarbital
    • Antimicrobial/fungal: aminoglycosides (e.g. amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomysin, streptomycin, tobramycin), rifampin
    • Anticoagulants/ Antiplatelets: warfarin
    • Others: methotrexate, nitroglycerin, St. John's wort, tyrosine kinase inhibitors, tacrine, diclofenac
  25. Participation in other clinical trials involving treatment for COVID-19. Note that institutional standard of care treatment of COVID-19 including glucocorticoids, hydroxychloroquine, azithromycin and/or remdesivir are not excluded from the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04476953
Other Study ID Numbers  ICMJE 20-003936
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party James L. Kirkland, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James L Kirkland Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP