<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/NCT04406545</url>
  </required_header>
  <id_info>
    <org_study_id>#CAAE 31237220.1.0000.5272</org_study_id>
    <nct_id>NCT04406545</nct_id>
  </id_info>
  <brief_title>Microvascular Flow and Reactivity in Patients Presenting in the Acute Phase of COVID-19.</brief_title>
  <official_title>Investigation of Systemic Microvascular Flow and Reactivity in Patients Presenting in the Acute Phase of Coronavirus Disease-19.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Cardiology, Laranjeiras, Brazil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Cardiology, Laranjeiras, Brazil</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Considering that the intensity of systemic microvascular changes in patients in the acute&#xD;
      phase of COVID-19 could be related to disease progression and prognosis, the present&#xD;
      cross-sectional and observational study aims to investigate the presence of endothelial&#xD;
      dysfunction in these patients, also looking for to evaluate associations between the presence&#xD;
      of endothelial dysfunction and demographic, clinical and laboratory variables.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An association between the presence of previous cardiovascular disease and adverse prognosis&#xD;
      has been demonstrated in patients with COVID-19 (coronavirus disease-19), presenting&#xD;
      increases of up to 5-10 times in mortality.&#xD;
&#xD;
      As an initial process, the SARS-CoV-2 virus, anchored in the transmembrane&#xD;
      angiotensin-converting enzyme 2 (ECA2), penetrates host cells, including endothelial cells,&#xD;
      pericytes and macrophages, in addition to type II pneumocytes.&#xD;
&#xD;
      Cellular invasion results in massive release of several pro-inflammatory cytokines (&quot;cytokine&#xD;
      storm&quot;), such as IL-1β, IFN-1 and IL-6, by the cells of the immune system. In turn, cytokines&#xD;
      increase the process of vascular inflammation and the expression of leukocyte-vascular&#xD;
      endothelium adhesion proteins, which results in endothelial activation accompanied by a&#xD;
      pro-coagulant and pro-adhesive phenotype - between leukocytes, platelets, red blood cells and&#xD;
      vascular endothelium - characteristic of the dysfunctional endothelium in the&#xD;
      microcirculation, which results in severe changes in the microvascular flow and, as a result,&#xD;
      in tissue perfusion.&#xD;
&#xD;
      It is also worth noting that the patients most vulnerable to the development of complications&#xD;
      are those with pre-existing endothelial dysfunction, associated with several risk factors&#xD;
      such as male gender and smoking, and comorbidities such as hypertension, diabetes and&#xD;
      obesity, all of which are associated with poor prognosis in COVID -19.&#xD;
&#xD;
      Considering that the intensity of systemic microvascular changes in patients in the acute&#xD;
      phase of COVID-19 could be related to disease progression and prognosis, the present&#xD;
      cross-sectional and observational study aims to investigate the presence of endothelial&#xD;
      dysfunction in these patients, also evaluating associations between the presence of&#xD;
      endothelial dysfunction and demographic, clinical and laboratory variables.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 15, 2020</start_date>
  <completion_date type="Actual">January 10, 2022</completion_date>
  <primary_completion_date type="Actual">January 10, 2022</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>To evaluate, through laser doppler, the presence of changes in systemic microvascular endothelial function in patients in the acute phase of COVID-19.</measure>
    <time_frame>Microvascular reactivity will be evaluated after a 20-minute rest in the supine position in a temperature-controlled room.</time_frame>
    <description>skin laser Doppler perfusion monitoring before and after local thermal hyperemia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate, using laser Doppler perfusion monitoring, the presence of changes in systemic microvascular endothelial function in patients twelve months after COVID-19 recovery.</measure>
    <time_frame>Microvascular reactivity will be evaluated after a 20-minute rest in the supine position in a temperature-controlled room</time_frame>
    <description>Skin laser Doppler perfusion monitoring before and after local thermal hyperemia</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Coronavirus Infection</condition>
  <condition>Endothelial Dysfunction</condition>
  <condition>Microvascular Rarefaction</condition>
  <arm_group>
    <arm_group_label>healthy volunteers</arm_group_label>
    <description>skin laser Doppler perfusion monitoring before and after local thermal hyperemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cardiovascular disease and COVID-19 infection</arm_group_label>
    <description>skin laser Doppler perfusion monitoring before and after local thermal hyperemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cardiovascular disease without COVID-19 infection</arm_group_label>
    <description>skin laser Doppler perfusion monitoring before and after local thermal hyperemia</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>evaluation of skin microvascular flow and reactivity</intervention_name>
    <description>evaluation of skin microvascular flow and reactivity using laser Doppler perfusion monitoring</description>
    <arm_group_label>cardiovascular disease and COVID-19 infection</arm_group_label>
    <arm_group_label>healthy volunteers</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      ultra frozen plasma samples will be stocked for the evaluation of inflammatory&#xD;
      anti-inflammatory cytokines&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        - We will include adult patients will with SARS-CoV-2 positive RT-PCR, admitted to the&#xD;
        hospital in a ward or intensive care unit.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  Age&gt; 18 years admitted to the hospital&#xD;
&#xD;
          -  SARS-CoV-2 positive real-time PCR molecular test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of non-COVID infection with systemic and microbiologically documented&#xD;
             repercussions.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Institute of Cardiology</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>21040-360</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>May 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>January 11, 2022</last_update_submitted>
  <last_update_submitted_qc>January 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Institute of Cardiology, Laranjeiras, Brazil</investigator_affiliation>
    <investigator_full_name>Eduardo Tibirica, MD, PhD</investigator_full_name>
    <investigator_title>Senior Researcher</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Microvascular Rarefaction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04406545
org study id: #CAAE 31237220.1.0000.5272
nct id: NCT04406545
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Considering that the intensity of systemic microvascular changes in patients in the acute
      phase of COVID-19 could be related to disease progression and prognosis, the present
      cross-sectional and observational study aims to investigate the presence of endothelial
      dysfunction in these patients, also looking for to evaluate associations between the presence
      of endothelial dysfunction and demographic, clinical and laboratory variables.
An association between the presence of previous cardiovascular disease and adverse prognosis
      has been demonstrated in patients with COVID-19 (coronavirus disease-19), presenting
      increases of up to 5-10 times in mortality.

      As an initial process, the SARS-CoV-2 virus, anchored in the transmembrane
      angiotensin-converting enzyme 2 (ECA2), penetrates host cells, including endothelial cells,
      pericytes and macrophages, in addition to type II pneumocytes.

      Cellular invasion results in massive release of several pro-inflammatory cytokines ("cytokine
      storm"), such as IL-1β, IFN-1 and IL-6, by the cells of the immune system. In turn, cytokines
      increase the process of vascular inflammation and the expression of leukocyte-vascular
      endothelium adhesion proteins, which results in endothelial activation accompanied by a
      pro-coagulant and pro-adhesive phenotype - between leukocytes, platelets, red blood cells and
      vascular endothelium - characteristic of the dysfunctional endothelium in the
      microcirculation, which results in severe changes in the microvascular flow and, as a result,
      in tissue perfusion.

      It is also worth noting that the patients most vulnerable to the development of complications
      are those with pre-existing endothelial dysfunction, associated with several risk factors
      such as male gender and smoking, and comorbidities such as hypertension, diabetes and
      obesity, all of which are associated with poor prognosis in COVID -19.

      Considering that the intensity of systemic microvascular changes in patients in the acute
      phase of COVID-19 could be related to disease progression and prognosis, the present
      cross-sectional and observational study aims to investigate the presence of endothelial
      dysfunction in these patients, also evaluating associations between the presence of
      endothelial dysfunction and demographic, clinical and laboratory variables.
observational model: Cohort
time perspective: Prospective
measure: To evaluate, through laser doppler, the presence of changes in systemic microvascular endothelial function in patients in the acute phase of COVID-19.
time frame: Microvascular reactivity will be evaluated after a 20-minute rest in the supine position in a temperature-controlled room.
description: skin laser Doppler perfusion monitoring before and after local thermal hyperemia
measure: To evaluate, using laser Doppler perfusion monitoring, the presence of changes in systemic microvascular endothelial function in patients twelve months after COVID-19 recovery.
time frame: Microvascular reactivity will be evaluated after a 20-minute rest in the supine position in a temperature-controlled room
description: Skin laser Doppler perfusion monitoring before and after local thermal hyperemia
arm group label: healthy volunteers
description: skin laser Doppler perfusion monitoring before and after local thermal hyperemia
arm group label: cardiovascular disease and COVID-19 infection
description: skin laser Doppler perfusion monitoring before and after local thermal hyperemia
arm group label: cardiovascular disease without COVID-19 infection
description: skin laser Doppler perfusion monitoring before and after local thermal hyperemia
intervention type: Other
intervention name: evaluation of skin microvascular flow and reactivity
description: evaluation of skin microvascular flow and reactivity using laser Doppler perfusion monitoring
arm group label: cardiovascular disease and COVID-19 infection
arm group label: healthy volunteers
ultra frozen plasma samples will be stocked for the evaluation of inflammatory
      anti-inflammatory cytokines
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: National Institute of Cardiology, Laranjeiras, Brazil
investigator full name: Eduardo Tibirica, MD, PhD
investigator title: Senior Researcher
mesh term: Coronavirus Infections
mesh term: Microvascular Rarefaction
sharing ipd: Undecided