Back to results

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

Primary Purpose

Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS), Respiratory Failure, Sars-CoV2

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Rapamycin

Placebo

About this trial

This is an interventional treatment trial for Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) focused on measuring COVID-19

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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
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:

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

Sites / Locations

University Hospital System
Audie L Murphy Memorial Veterans Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Rapamycin

Arm Description

Administration of placebo daily during hospitalization

Administration of rapamycin (sirolimus) 1mg daily during hospitalization

Outcomes

Primary Outcome Measures

Survival rate

The proportion of participants who survive without respiratory failure

Secondary Outcome Measures

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

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)

Full Information

NCT ID

NCT04482712

First Posted

July 21, 2020

Last Updated

May 27, 2021

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

The Claude D. Pepper Older Americans Independence Centers

1. Study Identification

Unique Protocol Identification Number

NCT04482712

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Withdrawn

Why Stopped

The study was never submitted to IRB or approved, due to feasibility issues

Study Start Date

April 2021 (Anticipated)

Primary Completion Date

January 2022 (Anticipated)

Study Completion Date

January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

The Claude D. Pepper Older Americans Independence Centers

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS), Respiratory Failure, Sars-CoV2

Keywords

COVID-19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

This is a double-blind clinical trial

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Administration of placebo daily during hospitalization

Arm Title

Rapamycin

Arm Type

Active Comparator

Arm Description

Administration of rapamycin (sirolimus) 1mg daily during hospitalization

Intervention Type

Drug

Intervention Name(s)

Rapamycin

Other Intervention Name(s)

Sirolimus, Rapamune, RAPA

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo Tablet or oral solution

Intervention Description

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

Primary Outcome Measure Information:

Title

Survival rate

Description

The proportion of participants who survive without respiratory failure

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Change in Clinical Status assessed by the World Health Organization (WHO) scale

Description

Time Frame

Baseline to 4 weeks

Title

Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

Description

Time Frame

Baseline to 4 weeks

Other Pre-specified Outcome Measures:

Title

All cause mortality

Description

Total number of deaths during the study period

Time Frame

4 weeks

Title

Duration of ECMO

Description

Number of days on ECMO

Time Frame

Up to 4 weeks

Title

Duration of supplemental oxygen

Description

Number of days participants are on supplemental oxygen

Time Frame

Up to 4 weeks

Title

Length of hospital stay

Description

Days of hospitalization

Time Frame

Up to 4 weeks

Title

Length of time to SARS-CoV2 negativity

Description

Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

Time Frame

Up to 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dean L Kellogg, MD, PhD

Organizational Affiliation

University of Texas Health at San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital System

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78228

Country

United States

Facility Name

Audie L Murphy Memorial Veterans Hospital

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All collected IPD, all IPD that underlie results in a publication will be shared.

IPD Sharing Time Frame

Data will become available at study completion at the time of journal publication.

Learn more about this trial

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

We'll reach out to this number within 24 hrs