COVID-FIS: Pilot in COVID-19 (SARS-CoV-2) of Fisetin in Older Adults in Nursing Homes

This study is a pilot, randomized, placebo-controlled, single-center study of Fisetin in elderly nursing home participants with non-, mildly-, or moderately-symptomatic and confirmed SARS-CoV-2 infection.

• Fisetin (Drug), also known as 3,3',4',7-tetrahydroxyflavone: \~20 mg/kg/day oral, NG or D tube course for 2 consecutive days twice (Days 0 \& 1 and Days 8 \& 9)
• Placebo (Drug): Placebo looks exactly like the treatment drug, but it contains no active ingredient

Primary outcomes

• Change in COVID-19 Severity [Baseline, Day 2, 8, 10, 14, 30, 90 and 180]: The Ordinal Scale for Clinical Improvement was used to assess change in COVID-19 Severity. The scale has a minimum value of 0 (no clinical or virological evidence of infection) and a maximum value of 8 (death) with higher scores indicating a worse outcome.

Sex: All, ages: 65 Years to any

Inclusion Criteria:

1. Men or post-menopausal women age ≥65 years.
2. Current nursing home resident.
3. CoV severity of moderate or less OR SpO2 ≥ 85% (on room air or ≤ 2 L of supplemental oxygen) at time of enrollment.
4. SARS-CoV-2 infection confirmed by mRNA-PCR test at Mayo Clinic or other CLIA certified laboratory, within 10 days before randomization.
5. Willing and able to provide written informed consent or have a legally authorized representative (LAR) who will provide informed consent.

Exclusion Criteria:

1. Presence of any condition that the Investigator or the subject's attending physician, physician's assistant, or nurse-practitioner believes would put the subject at risk or would preclude the patient from successfully completing the trial.
2. Pregnancy (note that only post-menopausal women will be enrolled).
3. Total bilirubin >3X upper limit of normal or as per clinical judgment.
4. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) >4x the upper limits of normal or as per clinical judgment.
5. Hemoglobin <7 g/dL; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥20,000/mm3 (≥20 x 109/L); platelet count ≤ 25,000/μL (≤25 x 109/L); absolute neutrophil count ≤1 x 109/L; lymphocyte count <0.3 x 109/L at screening or as per clinical judgment.
6. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine, immunological, or hepatic disorder.
7. eGFR <25 ml/ min/ 1.73 m2 or as per clinical judgment.
8. Plasma and/or serum glucose >300 or as per clinical judgment.
9. Human immunodeficiency virus infection.
10. Known active hepatitis B or C infection.
11. Invasive fungal infection.
12. Uncontrolled (as per clinical judgment) pleural/pericardial effusions or ascites.
13. History of diverticulitis or diverticulosis with GI bleeding, as per clinical judgment.
14. New/active invasive cancer except non-melanoma skin cancers as per clinical judgment.
15. Known condition associated with major immunodeficiency as per clinical judgment.
16. Known hypersensitivity or allergy to Fisetin.
17. Subjects taking any of the medications listed in the Investigator Brochure may participate if they are otherwise eligible AND the medication can be safely held during the following times:

    * Immediately before the 1st IP administration (Day 0) until at least 10 hours after the 2nd IP administration (Day 1)
    * Immediately before the 3rd IP administration (Day 8) until at least 10 hours after the 4th IP administration (Day 9)
18. Participation in other clinical trials involving treatment for COVID-19 (unless reviewed and approved by the Principle Investigator.) Note that institutional standard of care treatment of COVID-19 including glucocorticoids, hydroxychloroquine, azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not excluded from the study.

Participant flow

Outcome results

• Change in COVID-19 Severity (Primary), Mean, score on a scale: Treatment Group 1.88 +/- 0.31; Placebo Group 2 +/- 0

Adverse events

Time frame: Adverse events were collected from baseline to end of study for approximately 6 months (180 days) for all subjects.

Serious adverse events by term

Other adverse events by term

2 more terms not shown.

Limitations and caveats: Early Termination: The DSMB and NIA determined the study should be stopped due to futility.

• Study Protocol and Statistical Analysis Plan (PDF, 2023-05-26)
• Informed Consent Form (PDF, 2024-04-04)

• Brandon P Verdoorn, MD, Principal investigator, Mayo Clinic

NIH grants: R01AG072301