COVID-19
Conditions
Brief summary
The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 28 subjects were randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.
Interventions
DRUGSirolimus
Sirolimus 6mg daily on Day 1 followed by 2mg daily for the next 13 days for a total treatment duration of 14 days or hospital discharge, whatever happens sooner.
DRUGPlacebo
Matching placebo
Sponsors
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randmized, double blind, placebo controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects enrolled in the trial must meet all of the following criteria. * Confirmed COVID-19 pneumonia * Hypoxia as defined by room air oxygen saturation less than 92% or supplemental oxygen requirement * Presence of at least one additional biomarker that has been shown to predict poor prognosis: a) serum ferritin ≥500ug/l, b) LDH ≥250U/L, c) d-dimer ≥1ug/L, or d) lymphopenia as defined by absolute lymphocyte count \<1,000/uL * Age ≥ 18 years * Completed informed consent
Exclusion criteria
Subjects who meet ANY of the following criteria are not eligible for enrollment as study participants: * Known allergy or hypersensitivity to sirolimus * Inability or refusal to provide informed consent * Advanced respiratory support (high flow oxygen ≥ 15 L/min, CPAP, non-invasive or invasive mechanical ventilation) * Active enrollment in other interventional clinical drug trials. Co-enrollment in observational studies and biorepositories is allowed. * Pregnant women * Breast feeding * On chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants. A list of these medications is provided in Section 12.3.4 * Any clinically significant medical disease which in the opinion of the investigator precludes the patient from enrolling in the trial, including (but not limited to): * History of liver cirrhosis * End stage renal disease or need for renal replacement therapy * Decompensated heart failure * Known active tuberculosis or history of incompletely treated tuberculosis * Uncontrolled systemic bacterial or fungal infections * Active viral infection other than COVID-19
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Are Alive and Free From Advanced Respiratory Support Measures at Day 28. | 28 days | Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP\* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. \* CPAP use for known obstructive sleep apnea will not be considered as disease progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Surviving to Hospital Discharge | 28 days | Survival to hospital discharge |
| Drug Safety Profile | 28 days | Number of patients with adverse events |
| Duration of Hospital Stay | days | Length of hospitalization is measured as the number of days in the hospital from the date of randomization until the date of discharge or death from any cause, whichever came first, assessed up to 28 days post discharge. |
| Number of Patients Who Require Initiation of Off-label Therapies | 28 days | Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sirolimus Sirolimus 6mg on day 1 followed by 2mg daily for the next 13 days or until hospital discharge, whatever happens sooner.
Sirolimus: Sirolimus 6mg daily on Day 1 followed by 2mg daily for the next 13 days for a total treatment duration of 14 days or hospital discharge, whatever happens sooner. | 18 |
| Placebo Matching placebo
Placebo: Matching placebo | 10 |
| Total | 28 |
Baseline characteristics
| Characteristic | Placebo | Total | Sirolimus |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 14 | 57 years STANDARD_DEVIATION 14 | 57 years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 24 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 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 | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 21 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 1 / 10 |
| other Total, other adverse events | 9 / 18 | 5 / 10 |
| serious Total, serious adverse events | 3 / 18 | 2 / 10 |
Outcome results
Primary
Percentage of Patients Who Are Alive and Free From Advanced Respiratory Support Measures at Day 28.
Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP\* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. \* CPAP use for known obstructive sleep apnea will not be considered as disease progression.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Percentage of Patients Who Are Alive and Free From Advanced Respiratory Support Measures at Day 28. | 15 Participants |
| Placebo | Percentage of Patients Who Are Alive and Free From Advanced Respiratory Support Measures at Day 28. | 8 Participants |
Secondary
Drug Safety Profile
Number of patients with adverse events
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Drug Safety Profile | 9 Participants |
| Placebo | Drug Safety Profile | 5 Participants |
Secondary
Duration of Hospital Stay
Length of hospitalization is measured as the number of days in the hospital from the date of randomization until the date of discharge or death from any cause, whichever came first, assessed up to 28 days post discharge.
Time frame: days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sirolimus | Duration of Hospital Stay | 9.9 days | Standard Deviation 12.2 |
| Placebo | Duration of Hospital Stay | 12.9 days | Standard Deviation 11 |
Secondary
Number of Patients Who Require Initiation of Off-label Therapies
Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Number of Patients Who Require Initiation of Off-label Therapies | 0 Participants |
| Placebo | Number of Patients Who Require Initiation of Off-label Therapies | 0 Participants |
Secondary
Percentage of Patients Surviving to Hospital Discharge
Survival to hospital discharge
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus | Percentage of Patients Surviving to Hospital Discharge | 17 Participants |
| Placebo | Percentage of Patients Surviving to Hospital Discharge | 9 Participants |