<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/NCT04411433</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-19-FAV</org_study_id>
    <nct_id>NCT04411433</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19</brief_title>
  <official_title>An Open-Label, Multicenter, Parallel-Group, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ministry of Health, Turkey</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hacettepe University, Faculty of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Umraniye Education and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>SB Istanbul Education and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tepecik Training and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Istanbul University - Cerrahpasa (IUC)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ankara University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ankara City Hospital Bilkent</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ankara Training and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ege University Hospital (Application and Research Center)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kocaeli Derince Education and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Istanbul University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kayseri City Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ministry of Health, Turkey</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>
      This is an open-label, multicenter, parallel-group, randomized, phase III trial that&#xD;
      evaluates the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of&#xD;
      patients with possible or confirmed COVID-19 observed within the last 5 days. 1000 patients&#xD;
      will be randomized in 2:1:2:2:2:1 ratio and divided into six groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The clinical picture of 2019-nCoV disease is in a broad spectrum, which includes asymptomatic&#xD;
      infection, a mild upper respiratory tract infection, respiratory failure, and even severe&#xD;
      viral pneumonia with death. Although the mortality rate is not yet clear, the reported&#xD;
      case-fatality risk was 11-14% during the initial studies which included patients with severe&#xD;
      disease. The overall case fatality rate was reported as approximately 2%. In addition, most&#xD;
      cases have resulted in a pneumonia requiring supplemental oxygen therapy and ventilator&#xD;
      support. The alarming levels of spread and severity of COVID-19 caused a global emergency and&#xD;
      this outbreak has been characterized as a pandemic by the World Health Organization (WHO).&#xD;
&#xD;
      The investigational product Favipiravir is an antiviral drug against RNA viruses and has been&#xD;
      stated as effective for the treatment of COVID-19, first emerged from China, in various&#xD;
      clinical studies. In February 2020, Favipiravir was used for the clinical treatment of&#xD;
      COVID-19, has been shown to be more effective than the lopinavir / ritonavir combination in&#xD;
      80 people. In recent researches, the drug favipiravir is suggested that it may induce&#xD;
      recovery in a short time in patients with COVID-19-mild type and decrease the treatment&#xD;
      duration from 11 days to 4 days.&#xD;
&#xD;
      The investigational product hydroxychloroquine sulfate is a 4- aminoquinoline derivative and&#xD;
      widely used for the treatment of many rheumatic diseases such as rheumatoid arthritis and&#xD;
      systemic lupus erythematosus in addition to its antimalarial effects. In vitro studies&#xD;
      reported that hydroxychloroquine sulfate may be effective against many viruses, including&#xD;
      SARS-CoV-2 in many in vitro experiments. Additionally, preliminary results of limited number&#xD;
      of studies have been revealed that hydroxychloroquine sulfate reduces virus load and induces&#xD;
      improvement in patients with COVID-19. This agent has been also suggested to be used in&#xD;
      COVID-19 prophylaxis.&#xD;
&#xD;
      Until now, there is no official report on whether hydroxychloroquine combined with&#xD;
      favipiravir show clinical activity against the new coronavirus, COVID-19, in Turkey. The main&#xD;
      purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine and&#xD;
      favipiravir in the treatment of Turkey population with COVID-19.&#xD;
&#xD;
      This study designed as an open-label, multicenter, parallel-group, randomized, phase III&#xD;
      clinical drug trial.&#xD;
&#xD;
      A total of 1000 subjects aged between 18 to 70 years with symptoms and complaints consistent&#xD;
      with possible or confirmed COVID-19 observed within the last 5 days and meet all eligibility&#xD;
      criteria will participate in the study.&#xD;
&#xD;
      This study will be conducted in 14 sites.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 8, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>This is an open-label, multicenter, parallel-group, randomized, phase III trial that evaluates the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of patients with possible or confirmed COVID-19 observed within the last 5 days. 1000 patients will be randomized in 2:1:2:2:2:1 ratio and divided into six groups.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to recovery (discharge)</measure>
    <time_frame>14 days</time_frame>
    <description>The evaluation of recovery (discharge) period until 14th day after administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decrease in viral load</measure>
    <time_frame>14 days</time_frame>
    <description>The evaluation of decrease in viral load until 14th day after administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment</measure>
    <time_frame>14 days</time_frame>
    <description>Number/characteristics of Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment due to study drug from baseline until the end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of occurrence of lymphopenia from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of occurrence of lymphopenia from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of occurrence of thrombocytopenia from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of occurrence of thrombocytopenia from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in alanine aminotransferase (ALT) levels from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of ALT levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in aspartate aminotransferase (AST) levels from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of AST levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in C-reactive protein (CRP) levels from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of CRP levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in level of D-dimer levels from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of D-dimer levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in prothrombin time (PT) values from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of PT values for blood to coagulate from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in partial thromboplastin time (PTT) values from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of PTT values for blood to coagulate from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood pressure from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of systolic and diastolic blood pressure levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in respiratory rate from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of respiratory rate levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pulse oxymetry from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of pulse oxymetry levels from baseline until the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fever from baseline</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical evaluation of changes in fever from baseline until the end of study.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">1008</enrollment>
  <condition>Sars-CoV2</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Favipiravir (3200 mg + 1200 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Favipiravir (3600 mg + 1600 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Favipiravir combined with Hydroxychloroquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Favipiravir combined with Azithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).&#xD;
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroxychloroquine combined with Azithromycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).&#xD;
Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir (3200 mg + 1200 mg)</intervention_name>
    <description>Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
    <arm_group_label>Favipiravir (3200 mg + 1200 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir (3600 mg + 1600 mg)</intervention_name>
    <description>Drug: Favipiravir (3600 mg + 1600 mg) Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
    <arm_group_label>Favipiravir (3600 mg + 1600 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine</intervention_name>
    <description>Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
    <arm_group_label>Favipiravir combined with Hydroxychloroquine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Favipiravir (3200 mg + 1200 mg) combined with Azithromycin</intervention_name>
    <description>Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).&#xD;
Favipiravir Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.</description>
    <arm_group_label>Favipiravir combined with Azithromycin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).</description>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine combined with Azithromycin</intervention_name>
    <description>Drug: Hydroxychloroquine combined with Azithromycin Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).&#xD;
Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).&#xD;
Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).</description>
    <arm_group_label>Hydroxychloroquine combined with Azithromycin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects aged between 18 to 70 years,&#xD;
&#xD;
          -  Patients with symptoms and complaints consistent with possible or confirmed COVID- 19&#xD;
             observed within the last 5 days,&#xD;
&#xD;
          -  Patients with uncomplicated possible or confirmed COVID-19:&#xD;
&#xD;
               1. Symptoms such as fever, muscle aches, joint pain, cough, sore throat, nasal&#xD;
                  congestion, however no respiratory distress, no tachypnea or no SpO2 &lt; 93%,&#xD;
&#xD;
               2. Chest imaging (X-ray or CT chest) documented as normal&#xD;
&#xD;
          -  Patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia&#xD;
             symptoms):&#xD;
&#xD;
               1. Symptoms such as fever, muscle aches, joint pain, cough, sore throat, nasal&#xD;
                  congestion, as well as respiratory rate &lt;30/min and SpO2 above 93% on room air,&#xD;
&#xD;
               2. Chest imaging (X-ray or CT chest)-documented mild pneumonia symptoms&#xD;
&#xD;
          -  Patients who were decided to isolate and treat because of COVID-19 in the hospital,&#xD;
&#xD;
          -  Patients who have not been involved in any other interventional studies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients considered as inappropriate for this study for any reason like noncompliance&#xD;
             by the researcher,&#xD;
&#xD;
          -  Patients with persisting refractory nausea, vomiting, chronic diarrhoea or chronic&#xD;
             gastrointestinal disorders, inability to swallow the study drug which may affect&#xD;
             adequate absorption,&#xD;
&#xD;
          -  Patients with chronic liver disease: alanine aminotransferase (ALT)/aspartate&#xD;
             aminotransferase (AST) elevated over 5 times the upper limit of normal (ULN),&#xD;
&#xD;
          -  Patients with gout or hyperuricemia (above the ULN),&#xD;
&#xD;
          -  Patients with severe pneumonia symptoms,&#xD;
&#xD;
          -  Patients with known allergy to Favipiravir or for substances used in the study,&#xD;
&#xD;
          -  Patients did not receive specific antiviral drugs such as lopinavir/ritonavir,&#xD;
             ribavirin, arbidol, chloroquine phosphate, hydroxychloroquine, and monoclonal&#xD;
             antibodies within one week before admission.&#xD;
&#xD;
          -  Patients with known chronic renal impairment/failure [creatinine clearance (CcCl) &lt;30&#xD;
             mL/min],&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
&#xD;
          -  Patients undergoing cardiac ablation therapy&#xD;
&#xD;
          -  Patients using antiarrhythmic drugs&#xD;
&#xD;
          -  Patients actively receiving chemotherapy&#xD;
&#xD;
          -  Acute immunosuppressed patients&#xD;
&#xD;
          -  Patients undergoing psychosis therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hacettepe University, School of Medicine</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>January 29, 2021</last_update_submitted>
  <last_update_submitted_qc>January 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hacettepe University</investigator_affiliation>
    <investigator_full_name>Prof. Ates KARA, MD</investigator_full_name>
    <investigator_title>Prof.</investigator_title>
  </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>Azithromycin</mesh_term>
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Favipiravir</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04411433
org study id: COVID-19-FAV
nct id: NCT04411433
lead sponsor: 
collaborator: 
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has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, multicenter, parallel-group, randomized, phase III trial that
      evaluates the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of
      patients with possible or confirmed COVID-19 observed within the last 5 days. 1000 patients
      will be randomized in 2:1:2:2:2:1 ratio and divided into six groups.
The clinical picture of 2019-nCoV disease is in a broad spectrum, which includes asymptomatic
      infection, a mild upper respiratory tract infection, respiratory failure, and even severe
      viral pneumonia with death. Although the mortality rate is not yet clear, the reported
      case-fatality risk was 11-14% during the initial studies which included patients with severe
      disease. The overall case fatality rate was reported as approximately 2%. In addition, most
      cases have resulted in a pneumonia requiring supplemental oxygen therapy and ventilator
      support. The alarming levels of spread and severity of COVID-19 caused a global emergency and
      this outbreak has been characterized as a pandemic by the World Health Organization (WHO).

      The investigational product Favipiravir is an antiviral drug against RNA viruses and has been
      stated as effective for the treatment of COVID-19, first emerged from China, in various
      clinical studies. In February 2020, Favipiravir was used for the clinical treatment of
      COVID-19, has been shown to be more effective than the lopinavir / ritonavir combination in
      80 people. In recent researches, the drug favipiravir is suggested that it may induce
      recovery in a short time in patients with COVID-19-mild type and decrease the treatment
      duration from 11 days to 4 days.

      The investigational product hydroxychloroquine sulfate is a 4- aminoquinoline derivative and
      widely used for the treatment of many rheumatic diseases such as rheumatoid arthritis and
      systemic lupus erythematosus in addition to its antimalarial effects. In vitro studies
      reported that hydroxychloroquine sulfate may be effective against many viruses, including
      SARS-CoV-2 in many in vitro experiments. Additionally, preliminary results of limited number
      of studies have been revealed that hydroxychloroquine sulfate reduces virus load and induces
      improvement in patients with COVID-19. This agent has been also suggested to be used in
      COVID-19 prophylaxis.

      Until now, there is no official report on whether hydroxychloroquine combined with
      favipiravir show clinical activity against the new coronavirus, COVID-19, in Turkey. The main
      purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine and
      favipiravir in the treatment of Turkey population with COVID-19.

      This study designed as an open-label, multicenter, parallel-group, randomized, phase III
      clinical drug trial.

      A total of 1000 subjects aged between 18 to 70 years with symptoms and complaints consistent
      with possible or confirmed COVID-19 observed within the last 5 days and meet all eligibility
      criteria will participate in the study.

      This study will be conducted in 14 sites.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an open-label, multicenter, parallel-group, randomized, phase III trial that evaluates the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of patients with possible or confirmed COVID-19 observed within the last 5 days. 1000 patients will be randomized in 2:1:2:2:2:1 ratio and divided into six groups.
primary purpose: Treatment
masking: None (Open Label)
measure: Time to recovery (discharge)
time frame: 14 days
description: The evaluation of recovery (discharge) period until 14th day after administration.
measure: Decrease in viral load
time frame: 14 days
description: The evaluation of decrease in viral load until 14th day after administration.
measure: Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment
time frame: 14 days
description: Number/characteristics of Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment due to study drug from baseline until the end of study
measure: Frequency of occurrence of lymphopenia from baseline
time frame: 14 days
description: Clinical evaluation of occurrence of lymphopenia from baseline until the end of study.
measure: Frequency of occurrence of thrombocytopenia from baseline
time frame: 14 days
description: Clinical evaluation of occurrence of thrombocytopenia from baseline until the end of study.
measure: Changes in alanine aminotransferase (ALT) levels from baseline
time frame: 14 days
description: Clinical evaluation of ALT levels from baseline until the end of study.
measure: Changes in aspartate aminotransferase (AST) levels from baseline
time frame: 14 days
description: Clinical evaluation of AST levels from baseline until the end of study.
measure: Changes in C-reactive protein (CRP) levels from baseline
time frame: 14 days
description: Clinical evaluation of CRP levels from baseline until the end of study.
measure: Changes in level of D-dimer levels from baseline
time frame: 14 days
description: Clinical evaluation of D-dimer levels from baseline until the end of study.
measure: Changes in prothrombin time (PT) values from baseline
time frame: 14 days
description: Clinical evaluation of PT values for blood to coagulate from baseline until the end of study.
measure: Changes in partial thromboplastin time (PTT) values from baseline
time frame: 14 days
description: Clinical evaluation of PTT values for blood to coagulate from baseline until the end of study.
measure: Changes in blood pressure from baseline
time frame: 14 days
description: Clinical evaluation of systolic and diastolic blood pressure levels from baseline until the end of study.
measure: Changes in respiratory rate from baseline
time frame: 14 days
description: Clinical evaluation of respiratory rate levels from baseline until the end of study.
measure: Changes in pulse oxymetry from baseline
time frame: 14 days
description: Clinical evaluation of pulse oxymetry levels from baseline until the end of study.
measure: Changes in fever from baseline
time frame: 14 days
description: Clinical evaluation of changes in fever from baseline until the end of study.
arm group label: Favipiravir (3200 mg + 1200 mg)
arm group type: Experimental
description: Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir (3600 mg + 1600 mg)
arm group type: Experimental
description: Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir combined with Hydroxychloroquine
arm group type: Experimental
description: Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir combined with Azithromycin
arm group type: Experimental
description: Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Hydroxychloroquine
arm group type: Active Comparator
description: Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).
Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).
arm group label: Hydroxychloroquine combined with Azithromycin
arm group type: Active Comparator
description: Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).
Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).
Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).
intervention type: Drug
intervention name: Favipiravir (3200 mg + 1200 mg)
description: Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir (3200 mg + 1200 mg)
intervention type: Drug
intervention name: Favipiravir (3600 mg + 1600 mg)
description: Drug: Favipiravir (3600 mg + 1600 mg) Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).
The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir (3600 mg + 1600 mg)
intervention type: Drug
intervention name: Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine
description: Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).
Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir combined with Hydroxychloroquine
intervention type: Drug
intervention name: Favipiravir (3200 mg + 1200 mg) combined with Azithromycin
description: Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).
Favipiravir Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.
arm group label: Favipiravir combined with Azithromycin
intervention type: Drug
intervention name: Hydroxychloroquine
description: Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).
Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).
arm group label: Hydroxychloroquine
intervention type: Drug
intervention name: Hydroxychloroquine combined with Azithromycin
description: Drug: Hydroxychloroquine combined with Azithromycin Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).
Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).
Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).
arm group label: Hydroxychloroquine combined with Azithromycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Hacettepe University
investigator full name: Prof. Ates KARA, MD
investigator title: Prof.
mesh term: COVID-19
mesh term: Azithromycin
mesh term: Hydroxychloroquine
mesh term: Favipiravir