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

Respiratory Failure Clinical Trial

— RAPA-CARDS  

Official title:

Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04482712
• Other study ID #: HSC20200489H
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: April 2021
• Est. completion date: January 2023

Study information

• Verified date: May 2021
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2023
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Failure
• Respiratory Insufficiency
• Sars-CoV2
• Syndrome

Intervention

Drug:
• Rapamycin
Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized
• Placebo
Administration of investigational drug placebo for up to 4 weeks while hospitalized

Locations

Country	Name	City	State
United States	Audie L Murphy Memorial Veterans Hospital	San Antonio	Texas
United States	University Hospital System	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	The Claude D. Pepper Older Americans Independence Centers

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All cause mortality	Total number of deaths during the study period	4 weeks
Other	Duration of ECMO	Number of days on ECMO	Up to 4 weeks
Other	Duration of supplemental oxygen	Number of days participants are on supplemental oxygen	Up to 4 weeks
Other	Length of hospital stay	Days of hospitalization	Up to 4 weeks
Other	Length of time to SARS-CoV2 negativity	Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)	Up to 4 weeks
Primary	Survival rate	The proportion of participants who survive without respiratory failure	4 weeks
Secondary	Change in Clinical Status assessed by the World Health Organization (WHO) scale	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	Baseline to 4 weeks
Secondary	Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale	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)	Baseline to 4 weeks