<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/NCT04424992</url>
  </required_header>
  <id_info>
    <org_study_id>STORM</org_study_id>
    <nct_id>NCT04424992</nct_id>
  </id_info>
  <brief_title>The Natural History of Hospitalized COVID-19 Patients</brief_title>
  <acronym>STORM</acronym>
  <official_title>Observational Cohort Study on the Natural History of Hospitalized SARS-COV-2 Patients: the STORM Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milano Bicocca</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Milano Bicocca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an observational study. The aim is to describe the natural history and clinical&#xD;
      evolution over time of hospitalized patients affected by Severe Acute Respiratory&#xD;
      Syndrome-Coronavirus-2 (SARS-COV-2) infection, including the genetic pathology of the disease&#xD;
      and improve therapeutic procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
      As of the end of February 2020, the ASST of Monza, with its two hospital wards of Monza and&#xD;
      Desio, has treated 1433 COVID+ patients, of which 507 have currently been discharged (35.4%)&#xD;
      and 206 (14%) transferred to other Low-intensity care facilities.&#xD;
&#xD;
      The importance of observational studies is now known in many fields of medicine and the &quot;real&#xD;
      life&quot; data produced have become an integral part of the authorization dossiers by the&#xD;
      competent authorities to govern the introduction of new drugs: in particular, in a disease&#xD;
      such as that from COVID-19 in which the absence of specific anti-viral therapies prevents an&#xD;
      &quot;ad hoc&quot; cure, it becomes fundamental to identify and validate systems of stratification of&#xD;
      the risk of fatal events, in order to optimize health intervention measures.&#xD;
&#xD;
      METHODS AND STUDY DESIGN:&#xD;
&#xD;
      The study protocol provides the collection of clinical, diagnostic and therapeutic and&#xD;
      laboratory data consistent with the objectives of the study (CORE DATA SET) to which other&#xD;
      specific protocols and relative data will connect (DATABASE &quot;leaf&quot;). The data collection will&#xD;
      be performed on eCRF (RedCap platform) and the database will have the &quot;stem and leaf&quot;&#xD;
      structure, compatible with WHO indications regarding pandemic data collection.&#xD;
&#xD;
      CORE DATA SET:&#xD;
&#xD;
      The protocol presents two important aspects of innovation in its formulation and design:&#xD;
&#xD;
        1. The &quot;stem and leaf&quot; structure will allow to collect all the core data of the study&#xD;
           (&quot;stem&quot;) capable of describing the primary objective, that is the natural history of the&#xD;
           disease, thus providing an important contribution to knowledge, currently very scarce ,&#xD;
           the evolution of the disease;&#xD;
&#xD;
        2. the extreme heterogeneity of the pathology itself, the methods of spreading the&#xD;
           contagion and the problematic treatment of some particular patient populations, however&#xD;
           impose the description and the potential validation, not only in the context of subgroup&#xD;
           analyzes, but in studies dedicated, of the data collected The &quot;stem and leaf&quot; design&#xD;
           could therefore answer both questions.&#xD;
&#xD;
      BIOLOGICAL SAMPLE COLLECTION:&#xD;
&#xD;
      The biological research areas that the protocol proposes to pursue are listed below:&#xD;
&#xD;
        1. Study of genetic determinants of COVID-19 infection with the aim of identifying the&#xD;
           bases of the different susceptibility in relation to age, sex and presence of&#xD;
           co-morbidity;&#xD;
&#xD;
        2. Study of the repertoire of B and T lymphocyte receptors and identification of the&#xD;
           virus-specific sequences of the T receptor for the antigen with the aim of identifying&#xD;
           the component of the viral genome relevant to the immune response with possible relapses&#xD;
           for the development of a vaccine;&#xD;
&#xD;
        3. Study of the activation of the inflammosome responsible for the abnormal and severe&#xD;
           inflammatory response characteristic of patients with COVID-19 infection and serious&#xD;
           lung complications with the aim of identifying possible specific targets of intervention&#xD;
           against one or more inflammatory cytokines;&#xD;
&#xD;
        4. Study of the serological response during the acute phase of the disease and&#xD;
           convalescence with the aim of defining the possible state of protection from the disease&#xD;
           itself;&#xD;
&#xD;
        5. Study of the proteome with the aim of defining biomarkers capable of evaluate the risk&#xD;
           of progression.&#xD;
&#xD;
      STATISTICAL ANALYSIS:&#xD;
&#xD;
      For each specific protocol, the study design and statistical data analysis plan will be&#xD;
      formulated according to the specific objectives. In general, in addition to the descriptive&#xD;
      methods, statistical regression models and methods for the definition of prognostic scores&#xD;
      will be used, with relative cross-validation, which will allow to evaluate both binary and&#xD;
      survival outcomes (in a broad sense, of events considered in time).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 28, 2020</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Actual">December 28, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Covid19 infection clinical evolution</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Description over time of hospitalized patients suffering from SARS-COV-2 infection to better understand the pathogenesis of the disease and improve the controls and therapeutic procedures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Risk factors for intra-hospital mortality</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Identify risk factors for intra-hospital mortality in hospital wards COVID + patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The impact of a fragility index (IF)</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Assess the impact of a fragility index (IF) on the clinical course of COVID + patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognostic score</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year).</time_frame>
    <description>Build a prognostic score through which it is possible define a stratification that orients, according to the state of hospitalization, the therapeutic choices.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The lung sequelae of SARS-COV-2 pneumonia</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Differentiate the lung sequelae related to the evolution of viral damage from those of cheater / volutrauma connected to non-invasive (NIV-CPAP) or invasive (MV) ventilation methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The accuracy of IF in elderly patients</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Assess the accuracy of IF in elderly patients in terms of clinical outcomes compared to one clinical evaluation based on age and co-morbidity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation system anomalies</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Describe the anomalies of the coagulation system, which appear on patients affected by SARS-COV-2 pneumonia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The impact of the prone position on the oxygenation</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year)</time_frame>
    <description>Description of the impact of the prone position in terms of increased oxygenation of the patient suffering from SARS-COV-2 pneumonia as an index lung recruitment.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1433</enrollment>
  <condition>Sars-CoV2</condition>
  <arm_group>
    <arm_group_label>Covid19 infection related patients</arm_group_label>
    <description>The patients enrolled in the study are all patients with clinical and microbiological diagnosis of COVID-19 infection hospitalized since February 23, 2020 at San Gerardo Hospital (ASST-Monza).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Observational cohort study on the natural history of hospitalized SARS-COV-2 patients.</intervention_name>
    <description>Describe the natural history and clinical evolution of hospitalized patients over time affected by SARS-COV-2 infection, understand the pathogenesis of the disease and improve the aids and therapeutic procedures.</description>
    <arm_group_label>Covid19 infection related patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum from COVID+ patients&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The patients enrolled in the study are all patients with clinical and microbiological&#xD;
        diagnosis of COVID-19 infection hospitalized since February 23, 2020 at San Gerardo&#xD;
        Hospital (ASST-Monza).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical and / or radiological diagnosis of lung infection with COVID-19;&#xD;
&#xD;
          2. Positive test for SARS-CoV-2 infection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Age less than 18 years&#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_contact>
    <last_name>Paolo Bonfanti</last_name>
    <phone>+39 039 233 9310</phone>
    <email>paolo.bonfanti@unimib.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>ASST Monza-Ospedale San Gerardo</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paolo Bonfanti</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020 May 12;323(18):1775-1776. doi: 10.1001/jama.2020.4683. No abstract available. Erratum In: JAMA. 2020 Apr 28;323(16):1619.</citation>
    <PMID>32203977</PMID>
  </reference>
  <reference>
    <citation>Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.</citation>
    <PMID>32091533</PMID>
  </reference>
  <reference>
    <citation>Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017 Sep;20(3):252-259. doi: 10.1007/s10047-017-0967-4. Epub 2017 Jun 6.</citation>
    <PMID>28589286</PMID>
  </reference>
  <reference>
    <citation>Yuan FF, Tanner J, Chan PK, Biffin S, Dyer WB, Geczy AF, Tang JW, Hui DS, Sung JJ, Sullivan JS. Influence of FcgammaRIIA and MBL polymorphisms on severe acute respiratory syndrome. Tissue Antigens. 2005 Oct;66(4):291-6. doi: 10.1111/j.1399-0039.2005.00476.x.</citation>
    <PMID>16185324</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronavirus</keyword>
  <keyword>sars-covid-2</keyword>
  <keyword>coronavirus infection</keyword>
  <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/NCT04424992
org study id: STORM
nct id: NCT04424992
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is an observational study. The aim is to describe the natural history and clinical
      evolution over time of hospitalized patients affected by Severe Acute Respiratory
      Syndrome-Coronavirus-2 (SARS-COV-2) infection, including the genetic pathology of the disease
      and improve therapeutic procedures.
BACKGROUND:

      As of the end of February 2020, the ASST of Monza, with its two hospital wards of Monza and
      Desio, has treated 1433 COVID+ patients, of which 507 have currently been discharged (35.4%)
      and 206 (14%) transferred to other Low-intensity care facilities.

      The importance of observational studies is now known in many fields of medicine and the "real
      life" data produced have become an integral part of the authorization dossiers by the
      competent authorities to govern the introduction of new drugs: in particular, in a disease
      such as that from COVID-19 in which the absence of specific anti-viral therapies prevents an
      "ad hoc" cure, it becomes fundamental to identify and validate systems of stratification of
      the risk of fatal events, in order to optimize health intervention measures.

      METHODS AND STUDY DESIGN:

      The study protocol provides the collection of clinical, diagnostic and therapeutic and
      laboratory data consistent with the objectives of the study (CORE DATA SET) to which other
      specific protocols and relative data will connect (DATABASE "leaf"). The data collection will
      be performed on eCRF (RedCap platform) and the database will have the "stem and leaf"
      structure, compatible with WHO indications regarding pandemic data collection.

      CORE DATA SET:

      The protocol presents two important aspects of innovation in its formulation and design:

        1. The "stem and leaf" structure will allow to collect all the core data of the study
           ("stem") capable of describing the primary objective, that is the natural history of the
           disease, thus providing an important contribution to knowledge, currently very scarce ,
           the evolution of the disease;

        2. the extreme heterogeneity of the pathology itself, the methods of spreading the
           contagion and the problematic treatment of some particular patient populations, however
           impose the description and the potential validation, not only in the context of subgroup
           analyzes, but in studies dedicated, of the data collected The "stem and leaf" design
           could therefore answer both questions.

      BIOLOGICAL SAMPLE COLLECTION:

      The biological research areas that the protocol proposes to pursue are listed below:

        1. Study of genetic determinants of COVID-19 infection with the aim of identifying the
           bases of the different susceptibility in relation to age, sex and presence of
           co-morbidity;

        2. Study of the repertoire of B and T lymphocyte receptors and identification of the
           virus-specific sequences of the T receptor for the antigen with the aim of identifying
           the component of the viral genome relevant to the immune response with possible relapses
           for the development of a vaccine;

        3. Study of the activation of the inflammosome responsible for the abnormal and severe
           inflammatory response characteristic of patients with COVID-19 infection and serious
           lung complications with the aim of identifying possible specific targets of intervention
           against one or more inflammatory cytokines;

        4. Study of the serological response during the acute phase of the disease and
           convalescence with the aim of defining the possible state of protection from the disease
           itself;

        5. Study of the proteome with the aim of defining biomarkers capable of evaluate the risk
           of progression.

      STATISTICAL ANALYSIS:

      For each specific protocol, the study design and statistical data analysis plan will be
      formulated according to the specific objectives. In general, in addition to the descriptive
      methods, statistical regression models and methods for the definition of prognostic scores
      will be used, with relative cross-validation, which will allow to evaluate both binary and
      survival outcomes (in a broad sense, of events considered in time).
observational model: Cohort
time perspective: Prospective
measure: Covid19 infection clinical evolution
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Description over time of hospitalized patients suffering from SARS-COV-2 infection to better understand the pathogenesis of the disease and improve the controls and therapeutic procedures.
measure: Risk factors for intra-hospital mortality
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Identify risk factors for intra-hospital mortality in hospital wards COVID + patients.
measure: The impact of a fragility index (IF)
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Assess the impact of a fragility index (IF) on the clinical course of COVID + patients.
measure: Prognostic score
time frame: Until patient discharge from the hospital (approximately 1 year).
description: Build a prognostic score through which it is possible define a stratification that orients, according to the state of hospitalization, the therapeutic choices.
measure: The lung sequelae of SARS-COV-2 pneumonia
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Differentiate the lung sequelae related to the evolution of viral damage from those of cheater / volutrauma connected to non-invasive (NIV-CPAP) or invasive (MV) ventilation methods.
measure: The accuracy of IF in elderly patients
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Assess the accuracy of IF in elderly patients in terms of clinical outcomes compared to one clinical evaluation based on age and co-morbidity.
measure: Coagulation system anomalies
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Describe the anomalies of the coagulation system, which appear on patients affected by SARS-COV-2 pneumonia.
measure: The impact of the prone position on the oxygenation
time frame: Until patient discharge from the hospital (approximately 1 year)
description: Description of the impact of the prone position in terms of increased oxygenation of the patient suffering from SARS-COV-2 pneumonia as an index lung recruitment.
arm group label: Covid19 infection related patients
description: The patients enrolled in the study are all patients with clinical and microbiological diagnosis of COVID-19 infection hospitalized since February 23, 2020 at San Gerardo Hospital (ASST-Monza).
intervention type: Other
intervention name: Observational cohort study on the natural history of hospitalized SARS-COV-2 patients.
description: Describe the natural history and clinical evolution of hospitalized patients over time affected by SARS-COV-2 infection, understand the pathogenesis of the disease and improve the aids and therapeutic procedures.
arm group label: Covid19 infection related patients
Serum from COVID+ patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paolo Bonfanti
phone: +39 039 233 9310
email: paolo.bonfanti@unimib.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020 May 12;323(18):1775-1776. doi: 10.1001/jama.2020.4683. No abstract available. Erratum In: JAMA. 2020 Apr 28;323(16):1619.
PMID: 32203977
citation: Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
PMID: 32091533
citation: Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017 Sep;20(3):252-259. doi: 10.1007/s10047-017-0967-4. Epub 2017 Jun 6.
PMID: 28589286
citation: Yuan FF, Tanner J, Chan PK, Biffin S, Dyer WB, Geczy AF, Tang JW, Hui DS, Sung JJ, Sullivan JS. Influence of FcgammaRIIA and MBL polymorphisms on severe acute respiratory syndrome. Tissue Antigens. 2005 Oct;66(4):291-6. doi: 10.1111/j.1399-0039.2005.00476.x.
PMID: 16185324
responsible party type: Sponsor
sharing ipd: No