<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/NCT04405999</url>
  </required_header>
  <id_info>
    <org_study_id>05-20-02-С</org_study_id>
    <nct_id>NCT04405999</nct_id>
  </id_info>
  <brief_title>Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease</brief_title>
  <official_title>Prevention of Infection and Incidence of COVID-19 in Medical Personnel Assisting Patients With New Coronavirus Disease: a Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health</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 randomized controlled trial of the efficacy and safety evaluation of oral&#xD;
      administration of Bromhexine hydrochloride for the prevention of SARS-CoV-2 infection and&#xD;
      COVID-19 disease in medical personnel assisting patients with a new coronavirus disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims to evaluate the oral administration of Bromhexine hydrochloride for the&#xD;
      prevention of SARS-CoV-2 infection and COVID-19 disease in medical personnel assisting&#xD;
      patients with a new coronavirus disease. The aim of the study is to determine the preventive&#xD;
      role of this drug in the framework of reducing the incidence of coronavirus infection in risk&#xD;
      groups (medical personnel). Several studies show, that the acute respiratory syndrome&#xD;
      coronavirus SARS-CoV uses endosomal cysteine proteases cathepsin B and L (CatB/L) and the&#xD;
      transmembrane protease serine type 2 (TMPRSS2) for the priming of the viral S-protein. The&#xD;
      new coronavirus SARS-CoV-2 penetrates into alveolar epithelial type two cells through a&#xD;
      similar mechanism. In detail, viral S-protein binds to pneumocyte angiotensin-converting&#xD;
      enzyme 2 (ACE2) and then undergoes cleaving by TMPRSS2 in S1- and S2-subunits. This leads to&#xD;
      the release of a fusion peptide, which allows the virus to enter the cell via endocytosis.&#xD;
      Therefore, the protease TMPRSS2 can serve as a target for pharmacological agents to prevent&#xD;
      the penetration of the SARS-CoV-2 into the cell. Bromhexine blocks the TMPRSS2 ability to&#xD;
      activate a zymogen precursor of tissue plasminogen activator in vitro. Interestingly, TMPRSS2&#xD;
      is blocked by much lower concentrations then required to inactivate other proteases in the&#xD;
      cell culture. However, these data cannot be simply extended to the clinical practice: whether&#xD;
      the concentration of bromhexine in the lung tissue of properly treated patients would be&#xD;
      enough to prevent the virus entry through the TMPRSS2-inactivation remains unclear. A&#xD;
      randomized study in people at risk for coronavirus infection will clarify the role of&#xD;
      Bromhexine hydrochloride as a prevention of this disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 14, 2020</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 9, 2020</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Negative Polymerase Chain Reaction (PCR)</measure>
    <time_frame>4 weeks after randomization</time_frame>
    <description>Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Asymptomatic SARS-CoV-2 Infection</measure>
    <time_frame>14 days after last contact</time_frame>
    <description>Number of Participants with Asymptomatic SARS-CoV-2 Infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Mild, Moderate and Severe COVID-19 Disease</measure>
    <time_frame>14 days after last contact</time_frame>
    <description>number of participants with mild, moderate and severe COVID-19 disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>14 days after last contact</time_frame>
    <description>Number of Participants with Adverse Events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Increased Risk of SARS-CoV-2 Infection</condition>
  <arm_group>
    <arm_group_label>Bromhexine hydrochloride Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bromhexine Hydrochloride</intervention_name>
    <description>Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
    <arm_group_label>Bromhexine hydrochloride Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age of 18 years or more;&#xD;
&#xD;
          2. Negative test (PCR) for SARS-CoV-2 infection;&#xD;
&#xD;
          3. The absence of clinical manifestations of a respiratory infection;&#xD;
&#xD;
          4. Contact with patients with laboratory and / or clinically confirmed SARS-CoV-2&#xD;
             infection;&#xD;
&#xD;
          5. Signed informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intolerance to Bromhexine hydrochloride;&#xD;
&#xD;
          2. Work out of contact with SARS-CoV-2 infection;&#xD;
&#xD;
          3. Non-compliance with the rules for the use of personal protective equipment when&#xD;
             working with SARS-CoV-2 infection (the rules for the use of personal protective&#xD;
             equipment in accordance with the recommendations of the Ministry of Health of Russia&#xD;
             and the internal orders of the Director General of Almazov NMRC, relevant to the dates&#xD;
             of research);&#xD;
&#xD;
          4. Pregnancy and the period of breastfeeding;&#xD;
&#xD;
          5. Other circumstances that the researcher considers inappropriate to participate in this&#xD;
             study&#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>Evgeny Mikhaylov, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Almazov National Medical Research Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Almazov National Medical Research Centre</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <results_first_submitted>March 21, 2022</results_first_submitted>
  <results_first_submitted_qc>April 11, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bromhexine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 12, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT04405999/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment was performed via the institution's electronic communication system and via personal contacts with healthcare providers. Following a general notification via an institutional electronic system, one hundred and fifty healthcare providers were contacted personally and 50 persons were included.</recruitment_details>
      <pre_assignment_details>No subjects were excluded from the study before assignment to groups.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment Group</title>
          <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bromhexine Hydrochloride Group</title>
          <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
        </group>
        <group group_id="B2">
          <title>Control Group</title>
          <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.7" spread="6.9"/>
                    <measurement group_id="B2" value="39.5" spread="8.2"/>
                    <measurement group_id="B3" value="40.6" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Russia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Negative Polymerase Chain Reaction (PCR)</title>
        <description>Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization.</description>
        <time_frame>4 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Negative Polymerase Chain Reaction (PCR)</title>
          <description>Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Asymptomatic SARS-CoV-2 Infection</title>
        <description>Number of Participants with Asymptomatic SARS-CoV-2 Infection</description>
        <time_frame>14 days after last contact</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Asymptomatic SARS-CoV-2 Infection</title>
          <description>Number of Participants with Asymptomatic SARS-CoV-2 Infection</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Mild, Moderate and Severe COVID-19 Disease</title>
        <description>number of participants with mild, moderate and severe COVID-19 disease</description>
        <time_frame>14 days after last contact</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Mild, Moderate and Severe COVID-19 Disease</title>
          <description>number of participants with mild, moderate and severe COVID-19 disease</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Number of Participants with Adverse Events</description>
        <time_frame>14 days after last contact</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Number of Participants with Adverse Events</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected over 8 weeks.</time_frame>
      <desc>Overall number of participants affected by one or more Serious Adverse Events, for each arm/group.</desc>
      <group_list>
        <group group_id="E1">
          <title>Bromhexine Hydrochloride Group</title>
          <description>medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride&#xD;
Bromhexine Hydrochloride: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days</description>
        </group>
        <group group_id="E2">
          <title>Control Group</title>
          <description>medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute cough</sub_title>
                <description>Transient cough without sequelae. Drug treatment was not interrupted.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flash hot</sub_title>
                <description>A short period of hot flashes at treatment initiation without sequelae. Treatment was not interrupted.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Evgeny Mikhaylov</name_or_title>
      <organization>Almazov National Medical Research Centre</organization>
      <phone>+7(812)7023764</phone>
      <email>e.mikhaylov@almazovcentre.ru</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04405999
org study id: 05-20-02-С
nct id: NCT04405999
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized controlled trial of the efficacy and safety evaluation of oral
      administration of Bromhexine hydrochloride for the prevention of SARS-CoV-2 infection and
      COVID-19 disease in medical personnel assisting patients with a new coronavirus disease
This study aims to evaluate the oral administration of Bromhexine hydrochloride for the
      prevention of SARS-CoV-2 infection and COVID-19 disease in medical personnel assisting
      patients with a new coronavirus disease. The aim of the study is to determine the preventive
      role of this drug in the framework of reducing the incidence of coronavirus infection in risk
      groups (medical personnel). Several studies show, that the acute respiratory syndrome
      coronavirus SARS-CoV uses endosomal cysteine proteases cathepsin B and L (CatB/L) and the
      transmembrane protease serine type 2 (TMPRSS2) for the priming of the viral S-protein. The
      new coronavirus SARS-CoV-2 penetrates into alveolar epithelial type two cells through a
      similar mechanism. In detail, viral S-protein binds to pneumocyte angiotensin-converting
      enzyme 2 (ACE2) and then undergoes cleaving by TMPRSS2 in S1- and S2-subunits. This leads to
      the release of a fusion peptide, which allows the virus to enter the cell via endocytosis.
      Therefore, the protease TMPRSS2 can serve as a target for pharmacological agents to prevent
      the penetration of the SARS-CoV-2 into the cell. Bromhexine blocks the TMPRSS2 ability to
      activate a zymogen precursor of tissue plasminogen activator in vitro. Interestingly, TMPRSS2
      is blocked by much lower concentrations then required to inactivate other proteases in the
      cell culture. However, these data cannot be simply extended to the clinical practice: whether
      the concentration of bromhexine in the lung tissue of properly treated patients would be
      enough to prevent the virus entry through the TMPRSS2-inactivation remains unclear. A
      randomized study in people at risk for coronavirus infection will clarify the role of
      Bromhexine hydrochloride as a prevention of this disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Negative Polymerase Chain Reaction (PCR)
time frame: 4 weeks after randomization
description: Number of Participants with Negative PCR of SARS-CoV-2 and The Absence of Clinical Manifestations of COVID-19 Infection in individuals taking Bromhexine hydrochloride 4 weeks after randomization.
measure: Number of Participants With Asymptomatic SARS-CoV-2 Infection
time frame: 14 days after last contact
description: Number of Participants with Asymptomatic SARS-CoV-2 Infection
measure: Number of Participants With Mild, Moderate and Severe COVID-19 Disease
time frame: 14 days after last contact
description: number of participants with mild, moderate and severe COVID-19 disease
measure: Number of Participants With Adverse Events
time frame: 14 days after last contact
description: Number of Participants with Adverse Events
arm group label: Bromhexine hydrochloride Group
arm group type: Experimental
description: medical personnel at risk for COVID-19 infection with oral administration of Bromhexine hydrochloride
arm group label: Control Group
arm group type: No Intervention
description: medical personnel at risk for COVID-19 infection without oral administration of Bromhexine hydrochloride
intervention type: Drug
intervention name: Bromhexine Hydrochloride
description: Medical personnel at risk for COVID-19 infection will receive study medication for 14 days
arm group label: Bromhexine hydrochloride Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Evgeny Mikhaylov, MD, PhD
role: Study Director
affiliation: Almazov National Medical Research Centre
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Bromhexine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 