Table 1.

Study Summary

Title	COVID-FIS: A Phase 2 Placebo-Controlled Pilot Study in COVID-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Older Adults in Nursing Homes.
Running Title	COVID-FIS: COVID-19 Pilot Study of Fisetin to Alleviate Dysfunction and Inflammation.
Phase	Phase II.
Methodology	Randomized, placebo-controlled, double-blind secondary prevention trial.
Overall Study Duration	32 months.
Subject Participation Duration	Subject participation duration of 6 months (screening, 4 days treatment, follow-up visits, unblinded at the end of the study).
Single or Multi-Site	Multi-Site: Mayo Clinic Rochester and the other Translational Geroscience Network sites.
Objectives	● To prevent SARS-CoV-2 disease complications by a 7-point score adapted from the World Health Organization Ordinal Scale for Clinical Improvement of SARS-CoV-2 (see Supplemental Material). ● To evaluate safety and tolerability of Fisetin in this population. ● To reduce progression of severity of SARS-CoV-2 infections with no, mild, or moderate to severe or critical symptoms. ● To decrease senescent cells, inflammation, and physical dysfunction (frailty).
Primary Outcome	7-point ordinal severity scale adapted from the World Health Organization Ordinal Scale for Clinical improvement of SARS-CoV-2.
Secondary Outcomes	Measures of senescent cell abundance/inflammation, physical dysfunction/frailty, safety/tolerability, progression to severe/critical SARS-CoV-2, oxygenation and oxygen requirement, cell lysis syndrome, various laboratory parameters, chest imaging, need for acute hospital transfer, palliative care, intubation, or intensive care unit admission, and mortality.
Number of Subjects	250 enrolled and screened, 150 accrued and randomized.
Diagnosis and Main Inclusion Criteria	Age ≥ 65 years in a skilled nursing facility with test-proven SARS-CoV-2 infection. SpO2 ≥85% (on room air or ≤ 2 liters supplemental O2) at enrollment.
Study Product, Dose, Route, Regimen	This study will involve a 2-day oral or feeding tube course of Fisetin twice (~20 mg/kg/day for 2 consecutive days; Days 0, 1, 8, and 9).
Duration of Administration	4 out of 10 days.
Reference therapy	Placebo-controlled.
Statistical Methodology	Assuming 75 subjects/ group with a significance level of 0.05, the study will have 80% power to detect an odds ratio of 2.24 comparing the placebo- to Fisetin-treated group, using the 7-point severity score at Day 14 as the endpoint in an ordinal logistic regression model.