<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/NCT04423861</url>
  </required_header>
  <id_info>
    <org_study_id>NITFQM0920OR-III</org_study_id>
    <nct_id>NCT04423861</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Nitazoxanide 600 mg BID Versus Placebo for the Treatment of Hospitalized Patients With COVID-19</brief_title>
  <official_title>A Phase III, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Efficacy and Safety of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Non-critical Condition</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azidus Brasil</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Farmoquimica S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Azidus Brasil</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 pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID&#xD;
      compared to placebo to treat hospitalized patients with non-critical COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID compared&#xD;
      to placebo to treat hospitalized patients with non-critical COVID-19.&#xD;
&#xD;
      The aim is to demonstrate a decrease in hospital related complications among patients who are&#xD;
      hospitalized with moderate COVID-19 by treating them with nitazoxanide BID 600 mg for 7 days&#xD;
      on top of standard care compared to placebo on top of standar care..&#xD;
&#xD;
      Therefore, patients hospitalized with confirmed diagnosis of COVID-19 will be randomized to&#xD;
      receive either nitazoxanide 600 mg BID or Placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 22, 2022</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>Phase 3</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>Patients will be randomized to receive either nitazoxanide 600 mg BID or Placebo (1:1)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Need of mechanical ventilation</measure>
    <time_frame>14 days</time_frame>
    <description>Evaluation of change in acute respiratory syndrome using WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the pulmonary condition</measure>
    <time_frame>Baseline, Day 7 and Day 14</time_frame>
    <description>Evaluation of change in oximetry, respiratory rate and need for oxygen therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Condition</measure>
    <time_frame>Baseline, Day 7 and Day 14</time_frame>
    <description>Evaluation of change in the following symptoms: cough, headache, myalgia and fever, level of consciousness and organ dysfunction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in tomographic pulmonary condition</measure>
    <time_frame>Baseline, Day 7</time_frame>
    <description>Evaluation of change in chest CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of mortality within 14-days</measure>
    <time_frame>14 days</time_frame>
    <description>Evaluation of change in acute respiratory syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory markers</measure>
    <time_frame>Baseine, Day 7, Day 14</time_frame>
    <description>Evaluation of change in inflammatory markers d-dimer and IL-6</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">380</enrollment>
  <condition>covid19</condition>
  <arm_group>
    <arm_group_label>nitazoxanide BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive nitazoxanide 600 mg BID for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive matching placebo BID for 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitazoxanide</intervention_name>
    <description>Patients will receive nitazoxanide 600 mg BID for 7 days.</description>
    <arm_group_label>nitazoxanide BID</arm_group_label>
    <other_name>Viranitta (Nitazoxanide)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients will receive matching placebo BID for 7 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent from patient or legal representative.&#xD;
&#xD;
          2. Male or female, aged ≥ 18 years;&#xD;
&#xD;
          3. Laboratory confirmation of 2019-nCoV infection by reverse-transcription polymerase&#xD;
&#xD;
          4. chain reaction (RT-PCR) from any diagnostic sampling source;&#xD;
&#xD;
          5. Hospitalized for up to 48h with signs of respiratory failure with or without&#xD;
             non-invasive ventilation and i. Oxygen saturation &lt;98%;&#xD;
&#xD;
        7. Negative result for pregnancy test (if applicable).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participating in another RCT in the past 12 months;&#xD;
&#xD;
          2. Known allergy to nitazoxanide&#xD;
&#xD;
          3. Severely reduced LV function;&#xD;
&#xD;
          4. Severely reduced renal function;&#xD;
&#xD;
          5. Pregnancy or breast feeding;&#xD;
&#xD;
          6. Diagnosis of any other active infection (viral, bacterial, fungal or caused by another&#xD;
             pathogen, except the one studied in the trial);&#xD;
&#xD;
          7. History of HIV 1 and/or 2 (Anti-HIV-1,2) and/or HTLV I and II positive;&#xD;
&#xD;
          8. Ongoing antineoplastic treatment with chemotherapy or radiation therapy;&#xD;
&#xD;
          9. Diagnose of severe autoimmune diseases in immunosuppression;&#xD;
&#xD;
         10. Transplanted patients;&#xD;
&#xD;
         11. Any other clinical condition which, in the opinion of the principal investigator,&#xD;
             would not allow safe completion of the protocol and safe administration of the&#xD;
             investigational products&#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>Florentino de Araujo Cardoso Filho, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>+55 19 991232882</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Florentino de Araujo Cardoso Filho, MD, PhD</last_name>
    <phone>+55 19 991232882</phone>
    <email>florentino.cardoso@hospitalcare.com.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Luciana Ferrara</last_name>
    <phone>+55 19 981428814</phone>
    <email>luciana.ferrara@azidusbrasil.com.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Vera Cruz</name>
      <address>
        <city>Campinas</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florentino de Araujo Cardoso Filho, MD, PhD</last_name>
      <phone>+55 19 991232882</phone>
      <email>florentino.cardoso@hospitalcare.com.br</email>
    </contact>
    <contact_backup>
      <last_name>Luciana Ferrara</last_name>
      <phone>+55 19 981428814</phone>
      <email>luciana.ferrara@azidusbrasil.com.br</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>October 27, 2022</last_update_submitted>
  <last_update_submitted_qc>October 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 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>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nitazoxanide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.</ipd_description>
  </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/NCT04423861
org study id: NITFQM0920OR-III
nct id: NCT04423861
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID
      compared to placebo to treat hospitalized patients with non-critical COVID-19.
This is pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID compared
      to placebo to treat hospitalized patients with non-critical COVID-19.

      The aim is to demonstrate a decrease in hospital related complications among patients who are
      hospitalized with moderate COVID-19 by treating them with nitazoxanide BID 600 mg for 7 days
      on top of standard care compared to placebo on top of standar care..

      Therefore, patients hospitalized with confirmed diagnosis of COVID-19 will be randomized to
      receive either nitazoxanide 600 mg BID or Placebo.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomized to receive either nitazoxanide 600 mg BID or Placebo (1:1)
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Need of mechanical ventilation
time frame: 14 days
description: Evaluation of change in acute respiratory syndrome using WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)
measure: Change in the pulmonary condition
time frame: Baseline, Day 7 and Day 14
description: Evaluation of change in oximetry, respiratory rate and need for oxygen therapy
measure: Change in Clinical Condition
time frame: Baseline, Day 7 and Day 14
description: Evaluation of change in the following symptoms: cough, headache, myalgia and fever, level of consciousness and organ dysfunction
measure: Change in tomographic pulmonary condition
time frame: Baseline, Day 7
description: Evaluation of change in chest CT
measure: Rate of mortality within 14-days
time frame: 14 days
description: Evaluation of change in acute respiratory syndrome
measure: Change in inflammatory markers
time frame: Baseine, Day 7, Day 14
description: Evaluation of change in inflammatory markers d-dimer and IL-6
arm group label: nitazoxanide BID
arm group type: Experimental
description: Patients will receive nitazoxanide 600 mg BID for 7 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients will receive matching placebo BID for 7 days.
intervention type: Drug
intervention name: Nitazoxanide
description: Patients will receive nitazoxanide 600 mg BID for 7 days.
arm group label: nitazoxanide BID
other name: Viranitta (Nitazoxanide)
intervention type: Drug
intervention name: Placebo
description: Patients will receive matching placebo BID for 7 days.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Florentino de Araujo Cardoso Filho, MD, PhD
role: Principal Investigator
affiliation: +55 19 991232882
last name: Florentino de Araujo Cardoso Filho, MD, PhD
phone: +55 19 991232882
email: florentino.cardoso@hospitalcare.com.br
last name: Luciana Ferrara
phone: +55 19 981428814
email: luciana.ferrara@azidusbrasil.com.br
facility: 
status: Recruiting
contact: 
contact backup: 
country: Brazil
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Nitazoxanide
sharing ipd: Undecided
ipd description: It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.