Coronavirus Infection, Covid19
Conditions
Keywords
SARS-CoV-2
Brief summary
The purpose of this study is to test whether Fisetin, a senolytic drug can assist in the reduction of complications in patients with COVID-19 infection.
Detailed description
To determine whether short-term treatment with Fisetin reduces the rate of death and long term complications related to COVID-19 and to determine the safety of treatment with Fisetin in this patient population.
Interventions
DRUGFisetin
\ 20mg/kg /day oral for four days (days 0,1 and days 8,9)
DRUGPlacebo
Looks exactly like the study drug, but it contains no active ingredient . Oral for four days (days 0,1 and days 8,9)
Sponsors
James L. Kirkland, MD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females, at least 18 years of age, capable and willing to provide informed consent; * Patient must have received a diagnosis of COVID-19 infection within the last 3 days; * Outpatient setting (not currently hospitalized); * Patient must possess at least one of the following high-risk criteria: 60 years or more of age, obesity (BMI ≥ 30 kg/m2), diabetes mellitus, uncontrolled hypertension (systolic blood pressure ≥150 mm Hg), known respiratory disease (including asthma, chronic obstructive pulmonary disease, or present or past smoking), known heart failure, known coronary disease, fever of ≥38.4°C within the last 48 hours, dyspnea at the time of presentation, the combination of high neutrophil count and low lymphocyte count; * Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing at least one method of contraception and preferably two complementary forms of contraception including a barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, diaphragm, intrauterine device (IUD)) throughout the study and for 30 days after study completion; * Patient or their caregiver must be able and willing to comply with the requirements of this study protocol.
Exclusion criteria
* Patient currently hospitalized or under immediate consideration for hospitalization; * Patient currently in shock or with hemodynamic instability; * Patient with severe hepatic disease (as per clinical judgement) and liver enzymes \>10x the upper limit of normal; * Female patient who is pregnant, breast-feeding, or is considering becoming pregnant during the study or for 1 day after the last dose of study medication; * Patient currently taking Sirolimus, Tacrolimus, or other mTOR inhibitors for other indications (mainly chronic indications represented by organ transplantation or autoimmune diseases); * On Warfarin therapy; * Patient with a history of an allergic reaction or significant sensitivity to Fisetin; * Patient undergoing chemotherapy for cancer; * Patient is considered by the investigator, for any reason, to be an unsuitable study candidate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| World Health Organization (WHO) Ordinal Scale Score | 60 days | The number of subjects who scored as No limitations (Score 0-1) and Ambulatory, limitations (score 2-8) on the WHO Ordinal Scale score. The 9 points of the WHO ordinal clinical severity scale are as follows: 0: no clinical or virological evidence of infection; 1: ambulatory, no activity limitation; 2: ambulatory, activity limitation; 3: hospitalized, no oxygen therapy; 4: hospitalized, oxygen mask or nasal prongs; 5: hospitalized, noninvasive mechanical ventilation (NIMV) or high-flow nasal cannula (HFNC); 6: hospitalized, intubation and invasive mechanical ventilation (IMV); 7: hospitalized, IMV + additional support such as pressors or extracardiac membranous oxygenation (ECMO); 8: death. Total scores range from 0-8. Lower scales indicate less limitations, higher scores indicate more limitations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | 60 days | The number of serious adverse events reported |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Subjects who received treatment drug Fisetin
Fisetin: \
20mg/kg /day oral for four days (days 0,1 and days 8,9) | 29 |
| Placebo Subjects who received placebo
Placebo: Looks exactly like the study drug, but it contains no active ingredient. Oral for four days (days 0,1 and days 8,9) | 26 |
| Total | 55 |
Baseline characteristics
| Characteristic | Treatment Group | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 15.4 | 58.1 years STANDARD_DEVIATION 14.2 | 58.7 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 54 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 55 Participants | 26 Participants |
| Region of Enrollment United States | 29 participants | 55 participants | 26 participants |
| Sex: Female, Male Female | 19 Participants | 36 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 26 |
| other Total, other adverse events | 17 / 29 | 16 / 26 |
| serious Total, serious adverse events | 0 / 29 | 2 / 26 |
Outcome results
Primary
World Health Organization (WHO) Ordinal Scale Score
The number of subjects who scored as No limitations (Score 0-1) and Ambulatory, limitations (score 2-8) on the WHO Ordinal Scale score. The 9 points of the WHO ordinal clinical severity scale are as follows: 0: no clinical or virological evidence of infection; 1: ambulatory, no activity limitation; 2: ambulatory, activity limitation; 3: hospitalized, no oxygen therapy; 4: hospitalized, oxygen mask or nasal prongs; 5: hospitalized, noninvasive mechanical ventilation (NIMV) or high-flow nasal cannula (HFNC); 6: hospitalized, intubation and invasive mechanical ventilation (IMV); 7: hospitalized, IMV + additional support such as pressors or extracardiac membranous oxygenation (ECMO); 8: death. Total scores range from 0-8. Lower scales indicate less limitations, higher scores indicate more limitations.
Time frame: 60 days
Population: Two subjects in each arm did not return for the 60-day evaluation period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group | World Health Organization (WHO) Ordinal Scale Score | No limitations (Score 0-1) | 26 Participants |
| Treatment Group | World Health Organization (WHO) Ordinal Scale Score | Ambulatory, limitations (score 2-8) | 1 Participants |
| Placebo | World Health Organization (WHO) Ordinal Scale Score | No limitations (Score 0-1) | 22 Participants |
| Placebo | World Health Organization (WHO) Ordinal Scale Score | Ambulatory, limitations (score 2-8) | 2 Participants |
Secondary
Serious Adverse Events
The number of serious adverse events reported
Time frame: 60 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Serious Adverse Events | 0 number of serious adverse events |
| Placebo | Serious Adverse Events | 2 number of serious adverse events |