Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS), Respiratory Failure, Sars-CoV2
Conditions
Keywords
COVID-19
Brief summary
This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.
Detailed description
This is a single center, double-blind, placebo-controlled, randomized clinical trial in which each participant, after admission to hospital with a diagnosis of mild to moderate COVID-19 infection, will be administered either a dose of rapamycin or the placebo daily. Each subject will receive the assigned treatment until hospital discharge or death. Evaluations will be performed at the beginning of the clinical trial and then daily up to 4 weeks.
Interventions
DRUGRapamycin
Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized
DRUGPlacebo
Administration of investigational drug placebo for up to 4 weeks while hospitalized
Sponsors
The Claude D. Pepper Older Americans Independence Centers
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind clinical trial
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Over 60 years of age clinically judged to require hospitalization 2. SARS-CoV2 infection documented by positive RT-PCR nasopharyngeal swab 3. Mild to Moderate clinical status defined as clinical symptoms with or without pneumonia on imaging, with or without fever who are judged to require hospital admission 1. Elevated ferritin 2. Lymphopenia 3. Bilateral opacities on chest x-ray 4. Low pro-calcitonin 5. Clinical signs suggestive of symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea or moderate illness with CoVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) \> 93% on room air at sea level, heart rate ≥ 90 beats per minute.
Exclusion criteria
1. Known or suspected allergy to RAPA 2. High pro-calcitonin 3. SARS-CoV2 documented by negative RT-PCR nasopharyngeal swab 4. Treatment with contraindicated concomitant medications: currently receiving immunosuppressants, including steroids, prior to enrollment, or with immunomodulators or immunosuppressant drugs, including but not limited to Inter leukin (IL)-6 inhibitors, Tumor necrosis factor (TNF) inhibitors, anti-IL-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or 30 days (whichever is longer) prior to randomization. 5. Currently receiving immunosuppressants, including steroids, prior to enrollment 6. Serious underlying disease including but not limited to cardiac, pulmonary, renal, hepatic (bilirubin \>1.5x Upper normal limit (ULN) or Aspartate Aminotransferase (AST)\>ULN but bilirubin ≤ ULN), endocrine (diabetes) or psychiatric disorders judged to be at risk in participating by the inpatient attending physician or team 7. Suspected or confirmed history of alcohol or substance abuse disorder 8. Having participated in other drug trials in the past month 9. Deemed otherwise unsuitable for the study by researchers 10. Clinically judged to not require hospital admission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival rate | 4 weeks | The proportion of participants who survive without respiratory failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Status assessed by the World Health Organization (WHO) scale | Baseline to 4 weeks | The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8 |
| Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale | Baseline to 4 weeks | An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | Up to 4 weeks | Days of hospitalization |
| All cause mortality | 4 weeks | Total number of deaths during the study period |
| Length of time to SARS-CoV2 negativity | Up to 4 weeks | Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR) |
| Duration of ECMO | Up to 4 weeks | Number of days on ECMO |
| Duration of supplemental oxygen | Up to 4 weeks | Number of days participants are on supplemental oxygen |
Countries
United States
Outcome results
None listed