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

Sponsor

The University of Texas Health Science Center at San Antonio (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04482712

Collaborator

The Claude D. Pepper Older Americans Independence Centers (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Respiratory Failure Sars-CoV2	Drug: Rapamycin Drug: Placebo	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

This is a double-blind clinical trial

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Administration of placebo daily during hospitalization	Drug: Placebo Administration of investigational drug placebo for up to 4 weeks while hospitalized Other Names: Placebo Tablet or oral solution
Active Comparator: Rapamycin Administration of rapamycin (sirolimus) 1mg daily during hospitalization	Drug: Rapamycin Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized Other Names: Sirolimus Rapamune RAPA

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Administration of placebo daily during hospitalization

Drug: Placebo

Administration of investigational drug placebo for up to 4 weeks while hospitalized

Other Names:

Placebo Tablet or oral solution

Active Comparator: Rapamycin

Administration of rapamycin (sirolimus) 1mg daily during hospitalization

Drug: Rapamycin

Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized

Other Names:

Sirolimus

Rapamune

RAPA

Outcome Measures

Primary Outcome Measures

Survival rate [4 weeks]
The proportion of participants who survive without respiratory failure

Secondary Outcome Measures

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 Outcome Measures

All cause mortality [4 weeks]
Total number of deaths during the study period
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
Length of hospital stay [Up to 4 weeks]
Days of hospitalization
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Over 60 years of age clinically judged to require hospitalization
SARS-CoV2 infection documented by positive RT-PCR nasopharyngeal swab
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
Elevated ferritin
Lymphopenia
Bilateral opacities on chest x-ray
Low pro-calcitonin
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:

Known or suspected allergy to RAPA
High pro-calcitonin
SARS-CoV2 documented by negative RT-PCR nasopharyngeal swab
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.
Currently receiving immunosuppressants, including steroids, prior to enrollment
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
Suspected or confirmed history of alcohol or substance abuse disorder
Having participated in other drug trials in the past month
Deemed otherwise unsuitable for the study by researchers
Clinically judged to not require hospital admission