<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/NCT04412265</url>
  </required_header>
  <id_info>
    <org_study_id>FRA-COVID</org_study_id>
    <nct_id>NCT04412265</nct_id>
  </id_info>
  <brief_title>Frailty in Elderly Patients With COVID-19</brief_title>
  <acronym>FRA-COVID</acronym>
  <official_title>Relationship Between Frailty and Clinical Outcomes in Elderly Patients With COVID-19</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 a multicentric retro-prospective observational study that wants to evaluate the&#xD;
      relation between frailty and clinical outcomes in elderly patients with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
      Assessment of frailty is today the best way to evaluate the biological age of the elderly&#xD;
      person. Fragility can be defined as a syndrome selected by the reduction of organized&#xD;
      reserves and by the decreased resistance to &quot;stressors&quot;, resulting from the cumulative&#xD;
      decline of multiple physiological systems that cause vulnerabilities and adverse&#xD;
      consequences.&#xD;
&#xD;
      The impact of fragility on clinical outcomes has been investigated in numerous studies&#xD;
      conducted on elderly patients in various care setting, proving in all of them a significant&#xD;
      and more reliable predictor of variables such as age, comorbidity and individual pathologies,&#xD;
      short and long-term mortality, length of stay and the onset of complications.&#xD;
&#xD;
      Previous studies have already shown that frail older adults have a greater susceptibility to&#xD;
      viral infections (including non-COVID-19 coronavirus) due to a malfunction of their immune&#xD;
      system.&#xD;
&#xD;
      The identification of fragility could therefore be particularly useful for identifying&#xD;
      subjects at risk of negative outcomes (worsening of respiratory parameters, need for&#xD;
      intubation, mortality) even in a ward with COVID + patients. In other words, the&#xD;
      imperceptible clinical heterogeneity behind the age parameter could be better represented by&#xD;
      a multidimensional parameter capable of measuring the accumulation of age-related deficits.&#xD;
&#xD;
      SAMPLE SIZE (n. patients):&#xD;
&#xD;
      The study plans to recruit 30 subjects per week on average; for an expected total of about&#xD;
      300 subjects for each participating site.&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      The patient will be enrolled in the study when obtaining consent. In this phase the following&#xD;
      data will be collected:&#xD;
&#xD;
        -  date of birth&#xD;
&#xD;
        -  gender&#xD;
&#xD;
        -  demographic data&#xD;
&#xD;
        -  comorbidity&#xD;
&#xD;
        -  Brescia_COVID respiratory scale&#xD;
&#xD;
        -  modified Early Warning Score&#xD;
&#xD;
        -  delirium&#xD;
&#xD;
        -  data relating to functional autonomy&#xD;
&#xD;
        -  blood chemistry data at the entrance.&#xD;
&#xD;
      Using the variables that are part of the Comprehensive Geriatric Assessment, it will be&#xD;
      possible to calculate the Frailty Index (FI), according to the Rockwood deficit accumulation&#xD;
      model. A series of variables will then be collected relating to treatment procedures,&#xD;
      therapies, the team's choice to maximize the care ceiling for the individual patient and the&#xD;
      patient's clinical outcome.&#xD;
&#xD;
      Patients will be treated as per Normal Clinical Practice; no blood chemistry tests will be&#xD;
      required in addition to the panel of tests provided by the hospital's health management for&#xD;
      all patients with COVID-19.&#xD;
&#xD;
      Given the difficulty in systematically obtaining written informed consent and given the great&#xD;
      public interest of the project, the research will be conducted in the context of the&#xD;
      authorizations guaranteed by Article 89 of the GDPR EU Regulation 2016/679, which guarantees&#xD;
      the treatment for purposes of public interest, scientific or historical research or&#xD;
      statistical purposes of health data.&#xD;
&#xD;
      STATISTICAL ANALYSIS:&#xD;
&#xD;
      The FI will be built according to the Rockwood deficit accumulation model, taking into&#xD;
      account a minimum number of variables that are part of the Comprehensive Geriatric&#xD;
      Assessment. The FI will be obtained from the ratio between the number of pathological&#xD;
      conditions present and the total number of indicators evaluated. Data from patients older&#xD;
      than 60 years of age will be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2020</start_date>
  <completion_date type="Actual">December 15, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Development of a tool to measure frailty</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year).</time_frame>
    <description>The aim of the project is to evaluate whether a tool built to measure frailty in elderly patients admitted to the COVID + hospital wards is more accurate in predicting clinical states than a clinical evaluation developed on age and comorbidity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>A &quot;proxy&quot; variable of the fragility index can be built on the basis of regional administrative databases only.</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year).</time_frame>
    <description>Assess whether a &quot;proxy&quot; variable of the fragility index can be built on the basis of regional administrative databases only, which is able to predict the clinical outcomes of COVID + patients better than age and comorbidities alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Give elements to focus the screening policies for COVID19.</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year).</time_frame>
    <description>Relate different levels of chronicity with the susceptibility of the elderly subject to infection to give elements to focus the screening policies for COVID19.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Give the prevention of contagion at the elderly population level.</measure>
    <time_frame>Until patient discharge from the hospital (approximately 1 year).</time_frame>
    <description>Relate different levels of chronicity with the susceptibility of the elderly subject to infection to prevent the contagion at the elderly population level.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1344</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Covid 19 patients</arm_group_label>
    <description>The study will be conducted on all patients hospitalized affected by pneumonia COVID related.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Relation between frailty and clinical outcomes in elderly patients with COVID-19.</intervention_name>
    <description>To evaluate whether a tool built to measure frailty in elderly patients hospitalized in COVID + hospital departments are more accurate in predicting clinical outcomes compared to a clinical evaluation based on age and comorbidity. If the assessment of fragility were actually more accurate, the tool developed could be implemented in hospitals to support the clinician 's choices regarding the &quot;roof of care&quot; and actions to be taken undertake to prevent deterioration.</description>
    <arm_group_label>Covid 19 patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study will be conducted on all patients hospitalized in COVID+ departments of the&#xD;
        participating sites.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Diagnosis of COVID related pneumonia&#xD;
&#xD;
          -  Informed consent freely granted&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        - 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>
  <location>
    <facility>
      <name>Dipartimento di Geriatria, Fondazione Poliambulanza</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento di Medicina e Riabilitazione, Istituto Clinico Ospedale S. Anna</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UO Malattie Infettive, Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Medicina I a indirizzo Geriatrico, Spedali Civili</name>
      <address>
        <city>Montichiari</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Monza-Ospedale San Gerardo</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCDU Geriatria, AOU Città della Salute e della Scienza - Presidio Molinette</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8. Erratum In: Lancet. 2013 Oct 19;382(9901):1328.</citation>
    <PMID>23395245</PMID>
  </reference>
  <reference>
    <citation>Johnstone J, Parsons R, Botelho F, Millar J, McNeil S, Fulop T, McElhaney J, Andrew MK, Walter SD, Devereaux PJ, Malekesmaeili M, Brinkman RR, Mahony J, Bramson J, Loeb M. Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents. PLoS One. 2014 Oct 2;9(9):e108481. doi: 10.1371/journal.pone.0108481. eCollection 2014.</citation>
    <PMID>25275464</PMID>
  </reference>
  <reference>
    <citation>Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified Early Warning Score in medical admissions. QJM. 2001 Oct;94(10):521-6. doi: 10.1093/qjmed/94.10.521.</citation>
    <PMID>11588210</PMID>
  </reference>
  <reference>
    <citation>Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.</citation>
    <PMID>32167524</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 30, 2020</study_first_submitted>
  <study_first_submitted_qc>May 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>April 27, 2022</last_update_submitted>
  <last_update_submitted_qc>April 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 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>
  <keyword>geriatrics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Frailty</mesh_term>
  </condition_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/NCT04412265
org study id: FRA-COVID
nct id: NCT04412265
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multicentric retro-prospective observational study that wants to evaluate the
      relation between frailty and clinical outcomes in elderly patients with COVID-19.
BACKGROUND:

      Assessment of frailty is today the best way to evaluate the biological age of the elderly
      person. Fragility can be defined as a syndrome selected by the reduction of organized
      reserves and by the decreased resistance to "stressors", resulting from the cumulative
      decline of multiple physiological systems that cause vulnerabilities and adverse
      consequences.

      The impact of fragility on clinical outcomes has been investigated in numerous studies
      conducted on elderly patients in various care setting, proving in all of them a significant
      and more reliable predictor of variables such as age, comorbidity and individual pathologies,
      short and long-term mortality, length of stay and the onset of complications.

      Previous studies have already shown that frail older adults have a greater susceptibility to
      viral infections (including non-COVID-19 coronavirus) due to a malfunction of their immune
      system.

      The identification of fragility could therefore be particularly useful for identifying
      subjects at risk of negative outcomes (worsening of respiratory parameters, need for
      intubation, mortality) even in a ward with COVID + patients. In other words, the
      imperceptible clinical heterogeneity behind the age parameter could be better represented by
      a multidimensional parameter capable of measuring the accumulation of age-related deficits.

      SAMPLE SIZE (n. patients):

      The study plans to recruit 30 subjects per week on average; for an expected total of about
      300 subjects for each participating site.

      STUDY DESIGN:

      The patient will be enrolled in the study when obtaining consent. In this phase the following
      data will be collected:

        -  date of birth

        -  gender

        -  demographic data

        -  comorbidity

        -  Brescia_COVID respiratory scale

        -  modified Early Warning Score

        -  delirium

        -  data relating to functional autonomy

        -  blood chemistry data at the entrance.

      Using the variables that are part of the Comprehensive Geriatric Assessment, it will be
      possible to calculate the Frailty Index (FI), according to the Rockwood deficit accumulation
      model. A series of variables will then be collected relating to treatment procedures,
      therapies, the team's choice to maximize the care ceiling for the individual patient and the
      patient's clinical outcome.

      Patients will be treated as per Normal Clinical Practice; no blood chemistry tests will be
      required in addition to the panel of tests provided by the hospital's health management for
      all patients with COVID-19.

      Given the difficulty in systematically obtaining written informed consent and given the great
      public interest of the project, the research will be conducted in the context of the
      authorizations guaranteed by Article 89 of the GDPR EU Regulation 2016/679, which guarantees
      the treatment for purposes of public interest, scientific or historical research or
      statistical purposes of health data.

      STATISTICAL ANALYSIS:

      The FI will be built according to the Rockwood deficit accumulation model, taking into
      account a minimum number of variables that are part of the Comprehensive Geriatric
      Assessment. The FI will be obtained from the ratio between the number of pathological
      conditions present and the total number of indicators evaluated. Data from patients older
      than 60 years of age will be compared.
observational model: Case-Only
time perspective: Retrospective
measure: Development of a tool to measure frailty
time frame: Until patient discharge from the hospital (approximately 1 year).
description: The aim of the project is to evaluate whether a tool built to measure frailty in elderly patients admitted to the COVID + hospital wards is more accurate in predicting clinical states than a clinical evaluation developed on age and comorbidity.
measure: A "proxy" variable of the fragility index can be built on the basis of regional administrative databases only.
time frame: Until patient discharge from the hospital (approximately 1 year).
description: Assess whether a "proxy" variable of the fragility index can be built on the basis of regional administrative databases only, which is able to predict the clinical outcomes of COVID + patients better than age and comorbidities alone.
measure: Give elements to focus the screening policies for COVID19.
time frame: Until patient discharge from the hospital (approximately 1 year).
description: Relate different levels of chronicity with the susceptibility of the elderly subject to infection to give elements to focus the screening policies for COVID19.
measure: Give the prevention of contagion at the elderly population level.
time frame: Until patient discharge from the hospital (approximately 1 year).
description: Relate different levels of chronicity with the susceptibility of the elderly subject to infection to prevent the contagion at the elderly population level.
arm group label: Covid 19 patients
description: The study will be conducted on all patients hospitalized affected by pneumonia COVID related.
intervention type: Other
intervention name: Relation between frailty and clinical outcomes in elderly patients with COVID-19.
description: To evaluate whether a tool built to measure frailty in elderly patients hospitalized in COVID + hospital departments are more accurate in predicting clinical outcomes compared to a clinical evaluation based on age and comorbidity. If the assessment of fragility were actually more accurate, the tool developed could be implemented in hospitals to support the clinician 's choices regarding the "roof of care" and actions to be taken undertake to prevent deterioration.
arm group label: Covid 19 patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
citation: Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8. Erratum In: Lancet. 2013 Oct 19;382(9901):1328.
PMID: 23395245
citation: Johnstone J, Parsons R, Botelho F, Millar J, McNeil S, Fulop T, McElhaney J, Andrew MK, Walter SD, Devereaux PJ, Malekesmaeili M, Brinkman RR, Mahony J, Bramson J, Loeb M. Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents. PLoS One. 2014 Oct 2;9(9):e108481. doi: 10.1371/journal.pone.0108481. eCollection 2014.
PMID: 25275464
citation: Subbe CP, Kruger M, Rutherford P, Gemmel L. Validation of a modified Early Warning Score in medical admissions. QJM. 2001 Oct;94(10):521-6. doi: 10.1093/qjmed/94.10.521.
PMID: 11588210
citation: Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.
PMID: 32167524
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Frailty
sharing ipd: No