<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/NCT04417335</url>
  </required_header>
  <id_info>
    <org_study_id>NL73430.091.20</org_study_id>
    <secondary_id>2020-001591-15</secondary_id>
    <nct_id>NCT04417335</nct_id>
  </id_info>
  <brief_title>Reducing COVID-19 Related Hospital Admission in Elderly by BCG Vaccination</brief_title>
  <official_title>Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also&#xD;
      been shown to induce protection against various infections with a viral aetiology, leading to&#xD;
      significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might&#xD;
      be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease&#xD;
      severity in elderly people, who are known to be at increased risk of illness and death from&#xD;
      SARS-CoV-2 infection.&#xD;
&#xD;
      Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled&#xD;
      trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve&#xD;
      the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2)&#xD;
      outbreak a pandemic. The number of confirmed cases continues to rise, leading to significant&#xD;
      morbidity and mortality worldwide. Although individuals of any age can acquire SARS-CoV-2,&#xD;
      adults of middle age and older are most commonly affected. Moreover, recent reports&#xD;
      demonstrate that mortality rates rise significantly among patients 60 years and older.&#xD;
      Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences&#xD;
      in elderly are desperately needed. Bacillus Calmette-Guérin (BCG) vaccine not only protects&#xD;
      against tuberculosis, but has also been shown to induce protection against various infections&#xD;
      with a viral aetiology, leading to significant reductions in morbidity and mortality. We&#xD;
      hypothesize that BCG vaccination may reduce hospital admission and improve the clinical&#xD;
      course of symptoms of elderly people during the SARS-CoV-2 outbreak. Primary objective: To&#xD;
      reduce hospital admission of community dwelling older persons during the pandemic of&#xD;
      SARS-CoV-2. Secondary objective: To reduce disease severity, the duration of hospital&#xD;
      admission, ICU admission, or death in elderly during the pandemic of SARS-CoV-2.&#xD;
&#xD;
      Study design: A placebo-controlled adaptive multi-centre randomized controlled trial.&#xD;
&#xD;
      Study population: Elderly people (≥ 60 years of age). Intervention: Participants will be&#xD;
      randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 16, 2020</start_date>
  <completion_date type="Anticipated">May 2021</completion_date>
  <primary_completion_date type="Anticipated">May 2021</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>
    <intervention_model_description>placebo-controlled adaptive multi-centre randomized controlled trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>SARS-CoV-2 related hospital admission</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>the duration of hospital admission due to documented COVID-19</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the cumulative incidence of documented SARS-CoV-2 infection</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the cumulative incidence of self-reported acute respiratory symptoms or fever</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the cumulative incidence of death due to documented SARS-CoV-2 infection</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the cumulative incidence of hospital admission for any reason</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection</measure>
    <time_frame>Maximum of 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2014</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BCG vaccine (Danish strain 1331, SSI, Denmark)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% NaCl</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BCG vaccine</intervention_name>
    <description>Bacille Calmette-Guérin is a live attenuated strain of Mycobacterium bovis developed in 1921 to prevent tuberculosis and other mycobacterial related infections.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% NaCl</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult (≥ 60 years)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fever (&gt;38 ºC) within the past 24 hours&#xD;
&#xD;
          -  Suspicion of current active viral or bacterial infection&#xD;
&#xD;
          -  Expected vaccination during the first three months of the study period&#xD;
&#xD;
          -  Severely immunocompromised subjects. This exclusion category comprises: a) subjects&#xD;
             with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic&#xD;
             subjects with less than 500 neutrophils/mm3; c) subjects with solid organ&#xD;
             transplantation; d) subjects with bone marrow transplantation; e) subjects under&#xD;
             chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with&#xD;
             less than 400 lymphocytes/mm3; h) treatment with any immunosuppressant drugs such as&#xD;
             anti-cytokine therapies, and treatment with oral or intravenous steroids defined as&#xD;
             daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use&#xD;
             of oral or intravenous steroids in the following four weeks.&#xD;
&#xD;
          -  Active solid or non-solid malignancy or lymphoma within the prior two years&#xD;
&#xD;
          -  Active participation in another research study that involves BCG administration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Radboud University</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BCG</keyword>
  <keyword>Bacille Calmette-Guérin</keyword>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>trained immunity</keyword>
  <keyword>off-target effects</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>BCG Vaccine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04417335
org study id: NL73430.091.20
secondary id: 2020-001591-15
nct id: NCT04417335
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also
      been shown to induce protection against various infections with a viral aetiology, leading to
      significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might
      be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease
      severity in elderly people, who are known to be at increased risk of illness and death from
      SARS-CoV-2 infection.

      Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled
      trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve
      the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).
On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2)
      outbreak a pandemic. The number of confirmed cases continues to rise, leading to significant
      morbidity and mortality worldwide. Although individuals of any age can acquire SARS-CoV-2,
      adults of middle age and older are most commonly affected. Moreover, recent reports
      demonstrate that mortality rates rise significantly among patients 60 years and older.
      Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences
      in elderly are desperately needed. Bacillus Calmette-Guérin (BCG) vaccine not only protects
      against tuberculosis, but has also been shown to induce protection against various infections
      with a viral aetiology, leading to significant reductions in morbidity and mortality. We
      hypothesize that BCG vaccination may reduce hospital admission and improve the clinical
      course of symptoms of elderly people during the SARS-CoV-2 outbreak. Primary objective: To
      reduce hospital admission of community dwelling older persons during the pandemic of
      SARS-CoV-2. Secondary objective: To reduce disease severity, the duration of hospital
      admission, ICU admission, or death in elderly during the pandemic of SARS-CoV-2.

      Study design: A placebo-controlled adaptive multi-centre randomized controlled trial.

      Study population: Elderly people (≥ 60 years of age). Intervention: Participants will be
      randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: placebo-controlled adaptive multi-centre randomized controlled trial
primary purpose: Prevention
masking: Single (Participant)
measure: SARS-CoV-2 related hospital admission
time frame: Maximum of 1 year
measure: the duration of hospital admission due to documented COVID-19
time frame: Maximum of 1 year
measure: the cumulative incidence of documented SARS-CoV-2 infection
time frame: Maximum of 1 year
measure: the cumulative incidence of self-reported acute respiratory symptoms or fever
time frame: Maximum of 1 year
measure: the cumulative incidence of death due to documented SARS-CoV-2 infection
time frame: 1 year
measure: the cumulative incidence of hospital admission for any reason
time frame: Maximum of 1 year
measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection
time frame: Maximum of 1 year
arm group label: Treatment
arm group type: Experimental
description: BCG vaccine (Danish strain 1331, SSI, Denmark)
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.9% NaCl
intervention type: Biological
intervention name: BCG vaccine
description: Bacille Calmette-Guérin is a live attenuated strain of Mycobacterium bovis developed in 1921 to prevent tuberculosis and other mycobacterial related infections.
arm group label: Treatment
intervention type: Biological
intervention name: Placebo
description: 0.9% NaCl
arm group label: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: COVID-19
mesh term: BCG Vaccine
sharing ipd: No