<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04482712</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20200489H</org_study_id>
    <nct_id>NCT04482712</nct_id>
  </id_info>
  <brief_title>Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of ARDS</brief_title>
  <acronym>RAPA-CARDS</acronym>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Claude D. Pepper Older Americans Independence Centers</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR)&#xD;
      inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute&#xD;
      respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate&#xD;
      COVID-19 virus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, double-blind, placebo-controlled, randomized clinical trial in which&#xD;
      each participant, after admission to hospital with a diagnosis of mild to moderate COVID-19&#xD;
      infection, will be administered either a dose of rapamycin or the placebo daily. Each subject&#xD;
      will receive the assigned treatment until hospital discharge or death. Evaluations will be&#xD;
      performed at the beginning of the clinical trial and then daily up to 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study was never submitted to IRB or approved, due to feasibility issues&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2021</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This is a double-blind clinical trial</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Survival rate</measure>
    <time_frame>4 weeks</time_frame>
    <description>The proportion of participants who survive without respiratory failure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Status assessed by the World Health Organization (WHO) scale</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>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:&#xD;
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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>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:&#xD;
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 &amp;/or requiring supplemental home oxygen (7)&#xD;
Not hospitalized, no limitation on activities (8)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>All cause mortality</measure>
    <time_frame>4 weeks</time_frame>
    <description>Total number of deaths during the study period</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of ECMO</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Number of days on ECMO</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of supplemental oxygen</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Number of days participants are on supplemental oxygen</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Days of hospitalization</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of time to SARS-CoV2 negativity</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)</condition>
  <condition>Respiratory Failure</condition>
  <condition>Sars-CoV2</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Administration of placebo daily during hospitalization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rapamycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Administration of rapamycin (sirolimus) 1mg daily during hospitalization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapamycin</intervention_name>
    <description>Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized</description>
    <arm_group_label>Rapamycin</arm_group_label>
    <other_name>Sirolimus</other_name>
    <other_name>Rapamune</other_name>
    <other_name>RAPA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administration of investigational drug placebo for up to 4 weeks while hospitalized</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Tablet or oral solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Over 60 years of age clinically judged to require hospitalization&#xD;
&#xD;
          2. SARS-CoV2 infection documented by positive RT-PCR nasopharyngeal swab&#xD;
&#xD;
          3. Mild to Moderate clinical status defined as clinical symptoms with or without&#xD;
             pneumonia on imaging, with or without fever who are judged to require hospital&#xD;
             admission&#xD;
&#xD;
               1. Elevated ferritin&#xD;
&#xD;
               2. Lymphopenia&#xD;
&#xD;
               3. Bilateral opacities on chest x-ray&#xD;
&#xD;
               4. Low pro-calcitonin&#xD;
&#xD;
               5. Clinical signs suggestive of symptoms of mild illness with COVID-19 that could&#xD;
                  include fever, cough, sore throat, malaise, headache, muscle pain,&#xD;
                  gastrointestinal symptoms, without shortness of breath or dyspnea or moderate&#xD;
                  illness with CoVID-19, such as respiratory rate ≥ 20 breaths per minute,&#xD;
                  saturation of oxygen (SpO2) &gt; 93% on room air at sea level, heart rate ≥ 90 beats&#xD;
                  per minute.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known or suspected allergy to RAPA&#xD;
&#xD;
          2. High pro-calcitonin&#xD;
&#xD;
          3. SARS-CoV2 documented by negative RT-PCR nasopharyngeal swab&#xD;
&#xD;
          4. Treatment with contraindicated concomitant medications: currently receiving&#xD;
             immunosuppressants, including steroids, prior to enrollment, or with immunomodulators&#xD;
             or immunosuppressant drugs, including but not limited to Inter leukin (IL)-6&#xD;
             inhibitors, Tumor necrosis factor (TNF) inhibitors, anti-IL-1 agents and Janus kinase&#xD;
             (JAK) inhibitors within 5 half-lives or 30 days (whichever is longer) prior to&#xD;
             randomization.&#xD;
&#xD;
          5. Currently receiving immunosuppressants, including steroids, prior to enrollment&#xD;
&#xD;
          6. Serious underlying disease including but not limited to cardiac, pulmonary, renal,&#xD;
             hepatic (bilirubin &gt;1.5x Upper normal limit (ULN) or Aspartate Aminotransferase&#xD;
             (AST)&gt;ULN but bilirubin ≤ ULN), endocrine (diabetes) or psychiatric disorders judged&#xD;
             to be at risk in participating by the inpatient attending physician or team&#xD;
&#xD;
          7. Suspected or confirmed history of alcohol or substance abuse disorder&#xD;
&#xD;
          8. Having participated in other drug trials in the past month&#xD;
&#xD;
          9. Deemed otherwise unsuitable for the study by researchers&#xD;
&#xD;
         10. Clinically judged to not require hospital admission&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dean L Kellogg, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Health at San Antonio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital System</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Audie L Murphy Memorial Veterans Hospital</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>May 27, 2021</last_update_submitted>
  <last_update_submitted_qc>May 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All collected IPD, all IPD that underlie results in a publication will be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will become available at study completion at the time of journal publication.</ipd_time_frame>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04482712
org study id: HSC20200489H
nct id: NCT04482712
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: This is a double-blind clinical trial
measure: Survival rate
time frame: 4 weeks
description: The proportion of participants who survive without respiratory failure
measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale
time frame: Baseline to 4 weeks
description: 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
measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale
time frame: Baseline to 4 weeks
description: 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)
measure: All cause mortality
time frame: 4 weeks
description: Total number of deaths during the study period
measure: Duration of ECMO
time frame: Up to 4 weeks
description: Number of days on ECMO
measure: Duration of supplemental oxygen
time frame: Up to 4 weeks
description: Number of days participants are on supplemental oxygen
measure: Length of hospital stay
time frame: Up to 4 weeks
description: Days of hospitalization
measure: Length of time to SARS-CoV2 negativity
time frame: Up to 4 weeks
description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)
arm group label: Placebo
arm group type: Placebo Comparator
description: Administration of placebo daily during hospitalization
arm group label: Rapamycin
arm group type: Active Comparator
description: Administration of rapamycin (sirolimus) 1mg daily during hospitalization
intervention type: Drug
intervention name: Rapamycin
description: Daily administration of a dose of investigational drug for up to 4 weeks while hospitalized
arm group label: Rapamycin
other name: Sirolimus
other name: Rapamune
other name: RAPA
intervention type: Drug
intervention name: Placebo
description: Administration of investigational drug placebo for up to 4 weeks while hospitalized
arm group label: Placebo
other name: Placebo Tablet or oral solution
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Dean L Kellogg, MD, PhD
role: Principal Investigator
affiliation: University of Texas Health at San Antonio
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Respiratory Insufficiency
mesh term: Acute Lung Injury
mesh term: Lung Injury
mesh term: Syndrome
mesh term: Sirolimus
sharing ipd: Yes
ipd description: All collected IPD, all IPD that underlie results in a publication will be shared.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will become available at study completion at the time of journal publication.