<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/NCT04403646</url>
  </required_header>
  <id_info>
    <org_study_id>HCJSM-20-005</org_study_id>
    <nct_id>NCT04403646</nct_id>
  </id_info>
  <brief_title>Tannin Specific Natural Extract for COVID-19 Infection</brief_title>
  <acronym>TanCOVID</acronym>
  <official_title>Efficacy of Tannin Specific Natural Extract for Coronavirus Disease (COVID-19): Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas José de San Martín</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SILVATEAM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital de Clinicas José de San Martín</source>
  <oversight_info>
    <has_dmc>No</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>
      There is an urgent need to evaluate interventions that could be effective against the&#xD;
      infection with SARS-CoV 2. Tannins based wood extracts are an inexpensive and safe product&#xD;
      with protective effect in both bacterial and viral infections likely due to its anti-&#xD;
      inflammatory, anti-oxidative effects and their modulation of the intestinal microbiota. This&#xD;
      randomized controlled trial seeks to evaluate the efficacy of the tannins based dietary&#xD;
      supplement ARBOX in positive COVID-19 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The epidemic of 2019 novel coronavirus (causing the disease Covid-19) has expanded from Wuhan&#xD;
      throughout China and is being exported to a growing number of countries, some of which have&#xD;
      seen onward transmission. COVID-19 caused clusters of severe respiratory illness and was&#xD;
      associated with 2% mortality. There is currently no vaccine and no specific antiviral&#xD;
      treatment recommended for COVID-19. About 20% of the patients were severe and the mainstay of&#xD;
      clinical management is largely symptomatic treatment, with organ support in intensive care&#xD;
      for seriously ill patients. Therefore, it is urgent to find a safe and effective therapeutic&#xD;
      approach to COVID-19.&#xD;
&#xD;
      Tannins have been shown to have antioxidant, anti-inflammatory, antimicrobial properties and&#xD;
      a regulatory effect on the gastrointestinal metabolism.&#xD;
&#xD;
      The investigators will realize a prospective, double-blind, randomized trial to assess the&#xD;
      effect of treatment with a dietary supplement (ARBOX), a molecular complex of quebracho and&#xD;
      chestnut tannins extract and Vit B12, compared with placebo. 140 COVID-19 patients will be&#xD;
      recruited in a single center in Buenos Aires Argentina. 70 patients will receive conventional&#xD;
      treatment plus ARBOX (treated group) and 70 patients will receive conventional treatment plus&#xD;
      placebo (control group). The effects will be evaluated during the 28 days follow up. The&#xD;
      primary end point will be the time of discharge from the hospital. A panel of 27 cytokines&#xD;
      level, intestinal microbiota composition and its metabolites will be assessed at day 1 and&#xD;
      14.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low rate of covid patients&#xD;
  </why_stopped>
  <start_date type="Actual">June 12, 2020</start_date>
  <completion_date type="Actual">November 1, 2020</completion_date>
  <primary_completion_date type="Actual">October 20, 2020</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to hospital discharge</measure>
    <time_frame>Throughout the Study (Day 0 to Day 28)</time_frame>
    <description>defined as the time from first dose of polyphenol extract to hospital discharge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day all-cause mortality</measure>
    <time_frame>Throughout the Study (Day 0 to Day 28)</time_frame>
    <description>proportion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>invasive ventilation on day 28</measure>
    <time_frame>Throughout the Study (Day 0 to Day 28)</time_frame>
    <description>proportion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Pro and antiinflammatory citoquine levels</measure>
    <time_frame>day 1-14</time_frame>
    <description>mean difference</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in fecal intestinal microbiota composition</measure>
    <time_frame>day 1-14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Negativization of COVID-PCR at day 14</measure>
    <time_frame>day 14</time_frame>
    <description>proportion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">124</enrollment>
  <condition>COVID-19</condition>
  <condition>SARS-CoV 2</condition>
  <condition>Coronavirus Infection</condition>
  <arm_group>
    <arm_group_label>TREATED</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day and standard therapy.&#xD;
Standard treatment includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CONTROL</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo supply for 14 days. The placebo will be administrated with the identical dose as described for the test product.&#xD;
Beside patients will receive the standard theraphy, which includes Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>ARBOX</intervention_name>
    <description>dry extract of polyphenols (tannins) form quebracho and chestnut 240 mg, B12 vitamin 0.72 µg</description>
    <arm_group_label>TREATED</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PLACEBO</intervention_name>
    <description>Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for ARBOX</description>
    <arm_group_label>CONTROL</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Over 18 years of age hospitalized in the general hospitalization room, who meet the&#xD;
             definition of &quot;Confirmed case COVID-19&quot;&#xD;
             (https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion -of-case)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lactancy&#xD;
&#xD;
          -  Hypersensitivity to polyphenols&#xD;
&#xD;
          -  Patients unable to receive oral medication (severe cognitive impairment, assisted&#xD;
             ventilation, impaired state of consciousness)&#xD;
&#xD;
          -  Lack of consent&#xD;
&#xD;
          -  Participation in any other interventional clinical trial&#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>Maria M Piskorz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Clinicas Universidad de Buenos Aires</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital de Clinicas</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1120AAF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <reference>
    <citation>Theisen LL, Erdelmeier CA, Spoden GA, Boukhallouk F, Sausy A, Florin L, Muller CP. Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PLoS One. 2014 Jan 31;9(1):e88062. doi: 10.1371/journal.pone.0088062. eCollection 2014.</citation>
    <PMID>24498245</PMID>
  </reference>
  <reference>
    <citation>Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y, Sakaguchi T. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses. PLoS One. 2013;8(1):e55343. doi: 10.1371/journal.pone.0055343. Epub 2013 Jan 25.</citation>
    <PMID>23372851</PMID>
  </reference>
  <reference>
    <citation>Zhang L, Cheng YX, Liu AL, Wang HD, Wang YL, Du GH. Antioxidant, anti-inflammatory and anti-influenza properties of components from Chaenomeles speciosa. Molecules. 2010 Nov 22;15(11):8507-17. doi: 10.3390/molecules15118507.</citation>
    <PMID>21102377</PMID>
  </reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>December 19, 2020</last_update_submitted>
  <last_update_submitted_qc>December 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital de Clinicas José de San Martín</investigator_affiliation>
    <investigator_full_name>Maria Marta Piskorz</investigator_full_name>
    <investigator_title>Neurogastroenterologist at Hospital de Clinicas, Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</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/NCT04403646
org study id: HCJSM-20-005
nct id: NCT04403646
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
There is an urgent need to evaluate interventions that could be effective against the
      infection with SARS-CoV 2. Tannins based wood extracts are an inexpensive and safe product
      with protective effect in both bacterial and viral infections likely due to its anti-
      inflammatory, anti-oxidative effects and their modulation of the intestinal microbiota. This
      randomized controlled trial seeks to evaluate the efficacy of the tannins based dietary
      supplement ARBOX in positive COVID-19 patients.
The epidemic of 2019 novel coronavirus (causing the disease Covid-19) has expanded from Wuhan
      throughout China and is being exported to a growing number of countries, some of which have
      seen onward transmission. COVID-19 caused clusters of severe respiratory illness and was
      associated with 2% mortality. There is currently no vaccine and no specific antiviral
      treatment recommended for COVID-19. About 20% of the patients were severe and the mainstay of
      clinical management is largely symptomatic treatment, with organ support in intensive care
      for seriously ill patients. Therefore, it is urgent to find a safe and effective therapeutic
      approach to COVID-19.

      Tannins have been shown to have antioxidant, anti-inflammatory, antimicrobial properties and
      a regulatory effect on the gastrointestinal metabolism.

      The investigators will realize a prospective, double-blind, randomized trial to assess the
      effect of treatment with a dietary supplement (ARBOX), a molecular complex of quebracho and
      chestnut tannins extract and Vit B12, compared with placebo. 140 COVID-19 patients will be
      recruited in a single center in Buenos Aires Argentina. 70 patients will receive conventional
      treatment plus ARBOX (treated group) and 70 patients will receive conventional treatment plus
      placebo (control group). The effects will be evaluated during the 28 days follow up. The
      primary end point will be the time of discharge from the hospital. A panel of 27 cytokines
      level, intestinal microbiota composition and its metabolites will be assessed at day 1 and
      14.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time to hospital discharge
time frame: Throughout the Study (Day 0 to Day 28)
description: defined as the time from first dose of polyphenol extract to hospital discharge
measure: 28-day all-cause mortality
time frame: Throughout the Study (Day 0 to Day 28)
description: proportion
measure: invasive ventilation on day 28
time frame: Throughout the Study (Day 0 to Day 28)
description: proportion
measure: Difference in Pro and antiinflammatory citoquine levels
time frame: day 1-14
description: mean difference
measure: Difference in fecal intestinal microbiota composition
time frame: day 1-14
measure: Negativization of COVID-PCR at day 14
time frame: day 14
description: proportion
arm group label: TREATED
arm group type: Experimental
description: Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day and standard therapy.
Standard treatment includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy.
arm group label: CONTROL
arm group type: Placebo Comparator
description: Participants will receive placebo supply for 14 days. The placebo will be administrated with the identical dose as described for the test product.
Beside patients will receive the standard theraphy, which includes Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy.
intervention type: Dietary Supplement
intervention name: ARBOX
description: dry extract of polyphenols (tannins) form quebracho and chestnut 240 mg, B12 vitamin 0.72 µg
arm group label: TREATED
intervention type: Other
intervention name: PLACEBO
description: Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for ARBOX
arm group label: CONTROL
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria M Piskorz, MD
role: Principal Investigator
affiliation: Hospital de Clinicas Universidad de Buenos Aires
facility: 
country: Argentina
citation: Theisen LL, Erdelmeier CA, Spoden GA, Boukhallouk F, Sausy A, Florin L, Muller CP. Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PLoS One. 2014 Jan 31;9(1):e88062. doi: 10.1371/journal.pone.0088062. eCollection 2014.
PMID: 24498245
citation: Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y, Sakaguchi T. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses. PLoS One. 2013;8(1):e55343. doi: 10.1371/journal.pone.0055343. Epub 2013 Jan 25.
PMID: 23372851
citation: Zhang L, Cheng YX, Liu AL, Wang HD, Wang YL, Du GH. Antioxidant, anti-inflammatory and anti-influenza properties of components from Chaenomeles speciosa. Molecules. 2010 Nov 22;15(11):8507-17. doi: 10.3390/molecules15118507.
PMID: 21102377
responsible party type: Principal Investigator
investigator affiliation: Hospital de Clinicas José de San Martín
investigator full name: Maria Marta Piskorz
investigator title: Neurogastroenterologist at Hospital de Clinicas, Principal Investigator
mesh term: Infections
mesh term: COVID-19
mesh term: Coronavirus Infections
sharing ipd: Undecided