Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of ARDS

Phase 1

Withdrawn

• Conditions: Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Respiratory Failure; Sars-CoV2
• Interventions: Drug: Placebo; Drug: Rapamycin

• Registration Number: NCT04482712
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

Study Timeline

• Study First Submitted: 2020-07-21
• Study First Submitted QC: 2020-07-21
• Study First Posted: 2020-07-22
• Study Start: 2021-04
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-27
• Last Update Posted: 2021-06-01
• Primary Completion: 2022-01
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Administration of placebo daily during hospitalization
Rapamycin	Rapamycin	Administration of rapamycin (sirolimus) 1mg daily during hospitalization

Primary Outcome Measures

Name	Time	Method
Survival rate	4 weeks	The proportion of participants who survive without respiratory failure

Secondary Outcome Measures

Name	Time	Method
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)
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

Trial Locations

Locations (2)

University Hospital System; 🇺🇸 San Antonio, Texas, United States

Audie L Murphy Memorial Veterans Hospital; 🇺🇸 San Antonio, Texas, United States