Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo
Sirolimus	Sirolimus	Sirolimus 6mg on day 1 followed by 2mg daily for the next 13 days or until hospital discharge, whatever happens sooner.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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