<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/NCT04431466</url>
  </required_header>
  <id_info>
    <org_study_id>IFORS</org_study_id>
    <nct_id>NCT04431466</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Efficacy and Safety of Different Doses of Ivermectin for COVID-19</brief_title>
  <acronym>IFORS</acronym>
  <official_title>Phase 2 Clinical Trial to Compare the Efficacy and Safety of Different Doses of Ivermectin in Patients Diagnosed With the New Coronavirus Infection (SARS-CoV-2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal de Sao Carlos</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal de Sao Carlos</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>
      In December 2019, a group of patients with pneumonia of unknown cause was linked to a&#xD;
      wholesale seafood market in Wuhan, China. The genetic analysis of samples from the lower&#xD;
      respiratory tract of these patients indicated a new coronavirus as the causative agent, which&#xD;
      was named SARS-CoV-2. The virus spread rapidly to more than 45 countries, including Brazil,&#xD;
      causing an international alarm. However, in spite of its epidemiological magnitude, so far,&#xD;
      there is no antiviral treatment or vaccine approved for the treatment of this infection. With&#xD;
      about 15% to 20% of SARS-CoV-2 patients suffering from serious illnesses and overburdened&#xD;
      hospitals, therapeutic options are desperately needed. So, instead of creating compounds from&#xD;
      scratch that can take years to develop and test, researchers and public health agencies have&#xD;
      sought to redirect drugs already approved for other diseases and known to be widely safe. In&#xD;
      this context, the analysis of the international literature shows the existence of an in vitro&#xD;
      antiviral activity of ivermectin against SARS-CoV-2. However, there are no studies that have&#xD;
      evaluated its clinical effectiveness in patients diagnosed with SARS-CoV-2 infection.&#xD;
      Therefore, and considering this knowledge gap, the present study aims to determine the&#xD;
      clinical efficacy and safety of different doses of ivermectin in patients diagnosed with&#xD;
      SARS-CoV-2 infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Preliminary data from a pilot study suggest that the administration of ivermectin in patients&#xD;
    with SARS-CoV-2 is safe, reducing symptoms and viral load. The antiviral effects of ivermectin&#xD;
    appear to depend on the dose administered.&#xD;
  </why_stopped>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Undetectable viral load during 7 days of follow-up.</measure>
    <time_frame>7 days following intervention</time_frame>
    <description>Proportion of patients who achieved undetectable viral load during 7 days of follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral load variation in the nasopharyngeal swab.</measure>
    <time_frame>7 days following intervention.</time_frame>
    <description>Viral load variation in the nasopharyngeal swab during treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab.</measure>
    <time_frame>7 days following intervention.</time_frame>
    <description>Variation of serum lymphocyte counts during treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Self-reported Adverse Events</measure>
    <time_frame>28 days following intervention.</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events as assessed by clinical history and physical examination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Laboratory-based Adverse Events</measure>
    <time_frame>28 days following intervention.</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events as assessed by laboratory tests</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Coronavirus Infection</condition>
  <arm_group>
    <arm_group_label>Standard of care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care (SOC) treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC plus ivermectin 100 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SOC plus ivermectin 100 mcg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC plus ivermectin 200 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SOC plus ivermectin 200 mcg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC plus ivermectin 400 mcg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SOC plus ivermectin 400 mcg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivermectin</intervention_name>
    <description>SOC plus different dosing regimens of Ivermectin</description>
    <arm_group_label>SOC plus ivermectin 100 mcg/kg</arm_group_label>
    <arm_group_label>SOC plus ivermectin 200 mcg/kg</arm_group_label>
    <arm_group_label>SOC plus ivermectin 400 mcg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard treatment for COVID-19</description>
    <arm_group_label>Standard of care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of infection by SARS-CoV-2:&#xD;
&#xD;
               1. symptoms of acute respiratory tract infection (sudden onset of at least one of&#xD;
                  the following: cough, fever, shortness of breath) and biomolecular diagnosis of&#xD;
                  SARS-CoV-2 infection; OR&#xD;
&#xD;
               2. any acute respiratory disease AND biomolecular diagnosis of SARS-CoV-2 infection;&#xD;
                  OR&#xD;
&#xD;
               3. severe acute respiratory infection (fever and at least one sign / symptom of&#xD;
                  respiratory disease eg cough, fever, shortness of breath) AND in need of&#xD;
                  hospitalization AND biomolecular diagnosis of SARS-CoV-2 infection;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status score 0 to 1;&#xD;
&#xD;
          -  National Early Warning Score 0 to 4;&#xD;
&#xD;
          -  Ability to understand and consent to participate in this clinical trial, manifested by&#xD;
             signing the Informed Consent Form (ICF).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to ingest / absorb the study drug orally through spontaneous ingestion or&#xD;
             use of gastro / enteral tubes;&#xD;
&#xD;
          -  Any finding of clinical observation (history / physical evaluation) that is&#xD;
             interpreted by the investigating physician as a risk to participate in the trial;&#xD;
&#xD;
          -  Any laboratory test findings that the investigating physician considers as a risk to&#xD;
             the research participant as to his / her participation in the clinical study;&#xD;
&#xD;
          -  Any ECG examination finding that the investigating physician considers as a risk to&#xD;
             the research participant as to his / her participation in the trial;&#xD;
&#xD;
          -  Known hypersensitivity to the components of the drugs used during the study;&#xD;
&#xD;
          -  Women in pregnancy or breastfeeding;&#xD;
&#xD;
          -  Body weight less than 15kg;&#xD;
&#xD;
          -  Estimated glomerular filtration rate (CKD-Epidemiology Collaboration, CKD-EPI) &lt;30 mL&#xD;
             / min;&#xD;
&#xD;
          -  Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT)&gt; 5 times the&#xD;
             upper limit of normality;&#xD;
&#xD;
          -  Refusal to participate;&#xD;
&#xD;
          -  Refusal to sign the informed consent form.&#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>Henrique Pott Junior, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidade Federal de Sao Carlos</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Univeristário da Universidade Federal de São Carlos (HU-UFSCar)</name>
      <address>
        <city>São Carlos</city>
        <state>São Paulo</state>
        <zip>13565-905</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitário da Universidade Federal de São Carlos (HU-UFSCar)</name>
      <address>
        <city>São Carlos</city>
        <state>São Paulo</state>
        <zip>13566-448</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal de Sao Carlos</investigator_affiliation>
    <investigator_full_name>Henrique Pott Junior</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>coronavirus infections</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>COVID-19</keyword>
  <keyword>ivermectin</keyword>
  <keyword>clinical trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivermectin</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/NCT04431466
org study id: IFORS
nct id: NCT04431466
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
In December 2019, a group of patients with pneumonia of unknown cause was linked to a
      wholesale seafood market in Wuhan, China. The genetic analysis of samples from the lower
      respiratory tract of these patients indicated a new coronavirus as the causative agent, which
      was named SARS-CoV-2. The virus spread rapidly to more than 45 countries, including Brazil,
      causing an international alarm. However, in spite of its epidemiological magnitude, so far,
      there is no antiviral treatment or vaccine approved for the treatment of this infection. With
      about 15% to 20% of SARS-CoV-2 patients suffering from serious illnesses and overburdened
      hospitals, therapeutic options are desperately needed. So, instead of creating compounds from
      scratch that can take years to develop and test, researchers and public health agencies have
      sought to redirect drugs already approved for other diseases and known to be widely safe. In
      this context, the analysis of the international literature shows the existence of an in vitro
      antiviral activity of ivermectin against SARS-CoV-2. However, there are no studies that have
      evaluated its clinical effectiveness in patients diagnosed with SARS-CoV-2 infection.
      Therefore, and considering this knowledge gap, the present study aims to determine the
      clinical efficacy and safety of different doses of ivermectin in patients diagnosed with
      SARS-CoV-2 infection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Undetectable viral load during 7 days of follow-up.
time frame: 7 days following intervention
description: Proportion of patients who achieved undetectable viral load during 7 days of follow-up.
measure: Viral load variation in the nasopharyngeal swab.
time frame: 7 days following intervention.
description: Viral load variation in the nasopharyngeal swab during treatment.
measure: Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab.
time frame: 7 days following intervention.
description: Variation of serum lymphocyte counts during treatment.
measure: Incidence of Treatment-Emergent Self-reported Adverse Events
time frame: 28 days following intervention.
description: Incidence of Treatment-Emergent Adverse Events as assessed by clinical history and physical examination
measure: Incidence of Treatment-Emergent Laboratory-based Adverse Events
time frame: 28 days following intervention.
description: Incidence of Treatment-Emergent Adverse Events as assessed by laboratory tests
arm group label: Standard of care
arm group type: Active Comparator
description: Standard of care (SOC) treatment
arm group label: SOC plus ivermectin 100 mcg/kg
arm group type: Experimental
description: SOC plus ivermectin 100 mcg/kg
arm group label: SOC plus ivermectin 200 mcg/kg
arm group type: Experimental
description: SOC plus ivermectin 200 mcg/kg
arm group label: SOC plus ivermectin 400 mcg/kg
arm group type: Experimental
description: SOC plus ivermectin 400 mcg/kg
intervention type: Drug
intervention name: Ivermectin
description: SOC plus different dosing regimens of Ivermectin
arm group label: SOC plus ivermectin 100 mcg/kg
arm group label: SOC plus ivermectin 200 mcg/kg
arm group label: SOC plus ivermectin 400 mcg/kg
intervention type: Other
intervention name: Standard of Care
description: Standard treatment for COVID-19
arm group label: Standard of care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Henrique Pott Junior, MD PhD
role: Principal Investigator
affiliation: Universidade Federal de Sao Carlos
facility: 
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal de Sao Carlos
investigator full name: Henrique Pott Junior
investigator title: Professor
mesh term: Infections
mesh term: Coronavirus Infections
mesh term: Ivermectin
sharing ipd: No