<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/NCT04433078</url>
  </required_header>
  <id_info>
    <org_study_id>The STORM Trial</org_study_id>
    <nct_id>NCT04433078</nct_id>
  </id_info>
  <brief_title>RepurpoSing Old Drugs TO SuppRess a Modern Threat: COVID-19 STORM</brief_title>
  <acronym>STORM</acronym>
  <official_title>RepurpoSing Old Drugs TO SuppRess a Modern Threat: The STORM Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Temple University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Temple University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of this study is to test whether Doxycycline can benefit patients with severe&#xD;
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the&#xD;
      replication of the virus while at the same time blocking the development of cytokine storms&#xD;
      or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize&#xD;
      that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected&#xD;
      patients.&#xD;
&#xD;
      A secondary aim is to identify genetic variants that predict either an unusually mild disease&#xD;
      or an unusually severe disease - knowledge that can be used to design new and precise&#xD;
      medications and to be able to predict patients who might get into early trouble and to&#xD;
      therefore hospitalize them.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will randomize 20 patients with confirmed or highly suspected early stage severe&#xD;
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to Doxycycline (100 mg BID) or Placebo&#xD;
      and then assess the progression of their disease over the next three weeks with the primary&#xD;
      endpoint being days alive and out of the hospital.&#xD;
&#xD;
      The investigators will collect specimens for measurement of viral burden (nasopharyngeal&#xD;
      luminex (SARS-CoV-2), SARS-CoV-2 serum quantitative viral load, SARS-CoV-2 IgM/IgG&#xD;
      antibodies), markers of inflammation (WBC, ESR, TNFa, IL-1, IL-6, IL-1B), and cardiac&#xD;
      dysfunction (CRP, pro-BNP, hsTnT).&#xD;
&#xD;
      Eligibility will be based on history and physical examination findings - collated into a&#xD;
      clinical suspicion score. The decision to enroll based on clinical suspicion score rather&#xD;
      than confirmed SARS-CoV-2 disease is based on the variable and unacceptably high false&#xD;
      negative rate of the nasopharyngeal PCR test for in early disease.&#xD;
&#xD;
      Clinical Suspicion Score: Greater than or equal to 6/20 (at least 4 points of which must be&#xD;
      clinical) will be eligible for enrollment.&#xD;
&#xD;
      Clinical Criteria: Max 12 points&#xD;
&#xD;
        -  Fever (2 points)&#xD;
&#xD;
        -  Cough (2 points)&#xD;
&#xD;
        -  Dyspnea (2 points)&#xD;
&#xD;
        -  Chest pain (1 point)&#xD;
&#xD;
        -  Myalgias (1 point)&#xD;
&#xD;
        -  Fatigue (1 point)&#xD;
&#xD;
        -  GI symptoms (1 point)&#xD;
&#xD;
        -  Loss of Smell (1 point)&#xD;
&#xD;
        -  Loss of Taste (1 point)&#xD;
&#xD;
      Exposure Criteria: Max 8 points&#xD;
&#xD;
        -  Contact with known COVID+ (2 points)&#xD;
&#xD;
        -  Healthcare worker -- frequent &lt;6 feet contact for 15 minutes (2 points)&#xD;
&#xD;
        -  High-risk work -- supermarket, deli, transportation (2 points)&#xD;
&#xD;
        -  Endemic community -- prison/jail/nursing home/LTAC/SNF/rehab/homeless/homeless shelter&#xD;
           (2 points)&#xD;
&#xD;
      Genetic variants may explain why patients who are infected with SARS-CoV-2 have either a&#xD;
      relatively benign or an inappropriately aggressive response to an infectious insult.&#xD;
      Medications may be more or less effective in that group of patients harboring genetic&#xD;
      variants of a disease-related protein. To better understand this, whole genome sequencing and&#xD;
      analysis will be performed on all study patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No Participants Enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Actual">April 13, 2021</completion_date>
  <primary_completion_date type="Actual">April 13, 2021</primary_completion_date>
  <phase>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>
    <intervention_model_description>This study will randomize 20 patients with confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients to Doxycycline (100 mg BID) or Placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death</measure>
    <time_frame>21 days</time_frame>
    <description>Days Alive and Out of Hospital (Composite Endpoint)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>NP SARS-CoV-2 PCR</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SARS-CoV-2 Serum Quantitative Viral Load</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SARS-CoV-2 IgM/IgG Antibodies</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>White Blood Cell Count (WBC)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of White Blood Count (CBC) K/mm3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Lymphocyte Count (ALC)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive Protein (CRP)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of C-Reactive Protein (CRP) mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High Sensitivity Troponin I (hsTnT)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Necrosis Factor Alpha (TNF-a)</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-1</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of IL-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-1B</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of IL-1B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IL-6</measure>
    <time_frame>21 days</time_frame>
    <description>Change From Baseline of IL-6</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cytokine Storm</condition>
  <condition>SARS-CoV-2</condition>
  <arm_group>
    <arm_group_label>Doxycycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive 100 MG BID for 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive Placebo BID for 21 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxycycline</intervention_name>
    <description>100 MG Tablet</description>
    <arm_group_label>Doxycycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed or highly suspected early stage severe acute respiratory syndrome&#xD;
             coronavirus 2 (SARS-CoV-2), disease with clinical suspicion score &gt;6/20, not requiring&#xD;
             hospitalization&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Willing to sign the informed consent form&#xD;
&#xD;
          -  Willing to take study drug or placebo as directed for 21 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Confirmed or highly suspected early stage severe acute respiratory syndrome&#xD;
             coronavirus 2 (SARS-CoV-2), disease with clinical suspicion score &gt;6/20, requiring&#xD;
             hospitalization&#xD;
&#xD;
          -  Suspected or confirmed convalescent severe acute respiratory syndrome coronavirus 2&#xD;
             (SARS-CoV-2), within the prior 4 weeks&#xD;
&#xD;
          -  Age &lt;18 years' old&#xD;
&#xD;
          -  Inability to take medications orally&#xD;
&#xD;
          -  Inability to provide written consent&#xD;
&#xD;
          -  Known sensitivity/allergy to doxycycline or tetracyclines&#xD;
&#xD;
          -  Current use of doxycycline for another indication&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  A known diagnosis of myasthenia gravis&#xD;
&#xD;
          -  History of Clostridium Difficile infection within past 12 months&#xD;
&#xD;
          -  Sun sensitivity&#xD;
&#xD;
          -  Individuals using medications which could lower doxycycline levels, including&#xD;
             barbiturates, phenytoin, carbamazepine, warfarin&#xD;
&#xD;
          -  Individuals using isotretinoin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arthur M Feldman, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Temple University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Temple University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>April 13, 2021</last_update_submitted>
  <last_update_submitted_qc>April 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Doxycycline</keyword>
  <keyword>Cytokine Storm</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytokine Release Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxycycline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04433078
org study id: The STORM Trial
nct id: NCT04433078
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary aim of this study is to test whether Doxycycline can benefit patients with severe
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the
      replication of the virus while at the same time blocking the development of cytokine storms
      or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize
      that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected
      patients.

      A secondary aim is to identify genetic variants that predict either an unusually mild disease
      or an unusually severe disease - knowledge that can be used to design new and precise
      medications and to be able to predict patients who might get into early trouble and to
      therefore hospitalize them.
This study will randomize 20 patients with confirmed or highly suspected early stage severe
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to Doxycycline (100 mg BID) or Placebo
      and then assess the progression of their disease over the next three weeks with the primary
      endpoint being days alive and out of the hospital.

      The investigators will collect specimens for measurement of viral burden (nasopharyngeal
      luminex (SARS-CoV-2), SARS-CoV-2 serum quantitative viral load, SARS-CoV-2 IgM/IgG
      antibodies), markers of inflammation (WBC, ESR, TNFa, IL-1, IL-6, IL-1B), and cardiac
      dysfunction (CRP, pro-BNP, hsTnT).

      Eligibility will be based on history and physical examination findings - collated into a
      clinical suspicion score. The decision to enroll based on clinical suspicion score rather
      than confirmed SARS-CoV-2 disease is based on the variable and unacceptably high false
      negative rate of the nasopharyngeal PCR test for in early disease.

      Clinical Suspicion Score: Greater than or equal to 6/20 (at least 4 points of which must be
      clinical) will be eligible for enrollment.

      Clinical Criteria: Max 12 points

        -  Fever (2 points)

        -  Cough (2 points)

        -  Dyspnea (2 points)

        -  Chest pain (1 point)

        -  Myalgias (1 point)

        -  Fatigue (1 point)

        -  GI symptoms (1 point)

        -  Loss of Smell (1 point)

        -  Loss of Taste (1 point)

      Exposure Criteria: Max 8 points

        -  Contact with known COVID+ (2 points)

        -  Healthcare worker -- frequent <6 feet contact for 15 minutes (2 points)

        -  High-risk work -- supermarket, deli, transportation (2 points)

        -  Endemic community -- prison/jail/nursing home/LTAC/SNF/rehab/homeless/homeless shelter
           (2 points)

      Genetic variants may explain why patients who are infected with SARS-CoV-2 have either a
      relatively benign or an inappropriately aggressive response to an infectious insult.
      Medications may be more or less effective in that group of patients harboring genetic
      variants of a disease-related protein. To better understand this, whole genome sequencing and
      analysis will be performed on all study patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study will randomize 20 patients with confirmed or highly suspected early stage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients to Doxycycline (100 mg BID) or Placebo.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death
time frame: 21 days
description: Days Alive and Out of Hospital (Composite Endpoint)
measure: NP SARS-CoV-2 PCR
time frame: 21 days
description: Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)
measure: SARS-CoV-2 Serum Quantitative Viral Load
time frame: 21 days
description: Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load
measure: SARS-CoV-2 IgM/IgG Antibodies
time frame: 21 days
description: Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)
measure: White Blood Cell Count (WBC)
time frame: 21 days
description: Change From Baseline of White Blood Count (CBC) K/mm3
measure: Absolute Lymphocyte Count (ALC)
time frame: 21 days
description: Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3
measure: C-Reactive Protein (CRP)
time frame: 21 days
description: Change From Baseline of C-Reactive Protein (CRP) mg/dL
measure: N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP)
time frame: 21 days
description: Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL
measure: High Sensitivity Troponin I (hsTnT)
time frame: 21 days
description: Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL
measure: Tumor Necrosis Factor Alpha (TNF-a)
time frame: 21 days
description: Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)
measure: IL-1
time frame: 21 days
description: Change From Baseline of IL-1
measure: IL-1B
time frame: 21 days
description: Change From Baseline of IL-1B
measure: IL-6
time frame: 21 days
description: Change From Baseline of IL-6
arm group label: Doxycycline
arm group type: Experimental
description: Participants receive 100 MG BID for 21 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants receive Placebo BID for 21 days
intervention type: Drug
intervention name: Doxycycline
description: 100 MG Tablet
arm group label: Doxycycline
intervention type: Drug
intervention name: Placebo
description: Placebo Tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arthur M Feldman, MD, PhD
role: Principal Investigator
affiliation: Temple University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cytokine Release Syndrome
mesh term: Doxycycline
sharing ipd: No