Assessing the Efficacy of Sirolimus in Patients With COVID-19 Pneumonia for Prevention of Post-COVID Fibrosis

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to determine whether the drug sirolimus reduces the likelihood of developing of pulmonary fibrosis in patients who are hospitalized with COVID-19 pneumonia.

Detailed Description
-----------------
Hospitalized patients with a diagnosis of COVID-19 pneumonia will be referred to the study team for potential recruitment. Initial screening will take place using the existing medical record and in collaboration with the treating team. The study consists of 3 randomly assigned arms of varying dosages of the study drug All procedures, with the exception of drug dosing and option sample analysis, align with the subject's standard of care. Prior to initiating study drug, the subject's standard of care labs, imaging and oxygen requirements will be reviewed. Sirolimus will be administered as an oral medication. Subjects who are discharged prior to receiving 14 days of study drug will be provided with enough study drug to finish at home. On-study evaluation includes measurement of vital signs and laboratory studies before and after a patient has received sirolimus while inpatient. As part of routine care, subjects will be seen daily while in the hospital and will be monitored through blood tests for general health as well as renal function. Vital signs will be monitored daily while in the hospital, physical exams, assessment of COVID-19, and CT scans or chest x-rays as necessary for routine care. Subjects will return to clinic at 12 weeks for routine lab work and imaging as a part of study follow-up and will be assessed for pulmonary fibrosis at this time. Additionally, University of Chicago Medicine patients will have the option to allow investigators to use leftovers from tubes of blood drawn for clinical tests that would otherwise be discarded. This will apply to any blood collected during that respective hospital stay as well as up to 1 year after study enrollment.

Official Title
-----------------
SECOVID: A Multi-center, Randomized, Dose-ranging Parallel-group Trial Assessing the Efficacy of Sirolimus in Hospitalized Patients With COVID-19 Pneumonia for the Prevention of Post-COVID Fibrosis

Conditions
-----------------
Pulmonary Fibrosis, COVID-19 Pneumonia, Long COVID

Intervention / Treatment
-----------------
* Drug: Sirolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults ≥ 18 years of age Approval from the patient's primary inpatient service Hospitalized Diagnosed with COVID-19 pneumonia Positive test for active SARS-CoV-2 infection Requiring supplemental oxygen ≥ 5LNC or ≥ 40% FiO2. Chest computed tomography (CT) at admission with < 10% pulmonary fibrosis Ability to provide written informed consent on the part of the subject or, in the absence of decisional capacity of the subject, an appropriate surrogate (e.g. a legally authorized representative). Exclusion Criteria: Known diagnosis of previous pulmonary fibrosis or an interstitial lung disease. Clinical features or known diagnosis of malignancy or active non-COVID-19 infection, including untreated latent tuberculosis. History of unstable or deteriorating cardiac disease (including myocardial infarction, coronary artery bypass surgery or angioplasty within the past 6 months, congestive heart failure requiring hospitalization within the past 6 months, or uncontrolled arrhythmia. Known history of hypersensitivity to sirolimus. History of unstable or deteriorating neurologic disease (including TIAs or stroke). Pregnant or lactating females. Females of child bearing potential are required to have a negative pregnancy test prior to treatment and practice abstinence or prevent pregnancy by at least a barrier method of birth control. Investigational therapy for any indication within 28 days prior to treatment. Current treatment with any drugs that are strong inhibitors of CYP3A4. Tofacitinib Clarithromycin Telithromycin Nefazodone Itraconazole Ketoconazole Atazanavir Darunavir Indinavir Lopinavir Nelfinavir Ritonavir Saquinavir Tipranavir. Inability or unwillingness to comply with the requirements for the trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sirolimus 0.5mg<br>Subject will take Sirolimus 0.5mg orally daily for 14 days. | Drug: Sirolimus<br>* Triangular-shaped tablet<br>* Other names: RAPAMUNE;|
| Active Comparator: Sirolimus 1mg<br>Subject will take Sirolimus 1mg orally daily for 14 days. | Drug: Sirolimus<br>* Triangular-shaped tablet<br>* Other names: RAPAMUNE;|
| Active Comparator: Sirolimus 2mg<br>Subject will take Sirolimus 2mg orally daily for 14 days. | Drug: Sirolimus<br>* Triangular-shaped tablet<br>* Other names: RAPAMUNE;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Pulmonary Fibrosis as evidenced by CT scan | Number of patients with >10% pulmonary fibrosis on chest CT | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10% Threshold for Pulmonary Fibrosis evidenced by CT scan | Number of patients with >10% pulmonary fibrosis on chest CT | 12 Weeks | 
| Qualitative Fibrotic markers on chest CT | Number of patients with the presence or absence of chest CT imaging markers of fibrosis | 12 Weeks | 
| Quantitative Fibrosis Score on chest CT | Quantitative Fibrosis Score on chest CT | 12 Weeks | 
| Duration of Increased Supplemental Oxygen from Baseline | Number of days over which the participant requires supplemental oxygen in excess over baseline supplemental oxygen requirement. | 84 Days | 
| Pulmonary Function Test impairment | Number of subjects with the presence of abnormal indices of lung function tests | 12 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SECOVID, Sirolimus, Rapamune, Post-COVID Fibrosis, PASC