<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/NCT04407130</url>
  </required_header>
  <id_info>
    <org_study_id>PR-20039</org_study_id>
    <nct_id>NCT04407130</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Ivermectin and Doxycycline in Combination or IVE Alone in Patients With COVID-19 Infection.</brief_title>
  <official_title>Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Centre for Diarrhoeal Disease Research, Bangladesh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>International Centre for Diarrhoeal Disease Research, Bangladesh</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>
      Burden:&#xD;
&#xD;
      Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in&#xD;
      early December 2019.Presently known to be caused by a novel beta-corona virus, named as&#xD;
      Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2).&#xD;
&#xD;
      World Health Organization (WHO) declared a pandemic on March.&#xD;
&#xD;
      The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea&#xD;
      and pneumonia&#xD;
&#xD;
      Infected individuals exhibit:&#xD;
&#xD;
        1. Mostly mild illness (80% +) recover without any treatment (~80%)&#xD;
&#xD;
        2. Moderate illness that needs hospitalization and recovers after standard&#xD;
&#xD;
        3. supportive treatment (~14%)&#xD;
&#xD;
        4. Critical illness (~5%) needs ICU support&#xD;
&#xD;
        5. Death (1-2% )&#xD;
&#xD;
      COVID-19 has now spread &gt;210 countries and territories globally. SARS-CoV-2 is a respiratory&#xD;
      virus which spreads primarily through droplets generalized when an infected person coughs or&#xD;
      sneezes or through droplets of saliva or discharge from the nose.&#xD;
&#xD;
      Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be&#xD;
      more common in older individuals and those with co-morbidities, such as chronic lung disease,&#xD;
      cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at&#xD;
      risk for critical illness including multi-organ failure and death. Seen more in Bangladesh&#xD;
      between 21-40 yrs of age.&#xD;
&#xD;
      Knowledge Gap:&#xD;
&#xD;
      There is no specific treatment against this new virus that WHO has officially declared until&#xD;
      now.There are many pharmacologic therapies that are being used or considered for treatment of&#xD;
      COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19):&#xD;
      V 5.0 date 9th April 2020) CDC, DGHS, GoB&#xD;
&#xD;
      Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in&#xD;
      COVID-19 patients from other countries as well as its availability &amp; affordability of those&#xD;
      repurposed medicines&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      General Objective:&#xD;
&#xD;
      The aim of the study is to evaluate efficacy and safety of ivermectin in combination with&#xD;
      doxycycline or ivermectin alone for the treatment of hospitalized SARS-CoV-2 infected adult&#xD;
      Bangladeshi COVID-19 +ve patients and to compare with placebo; where all three arms will&#xD;
      receive the standard care of treatment of COVID-19 infected patients in the hospital. By&#xD;
      successful demonstration of the safety and efficacy of these repurposed medicines, it may&#xD;
      have the potential to play an important role in the treatment of COVID-19+ve patients.&#xD;
&#xD;
      Specific Objective:&#xD;
&#xD;
        1. Duration of the virological clearance rate&#xD;
&#xD;
        2. Days required for remission of fever and cough&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  Patients requiring oxygen&#xD;
&#xD;
        -  Patients failing to maintain SpO2 &gt;88 despite oxygenation&#xD;
&#xD;
        -  Number of days on oxygen support&#xD;
&#xD;
        -  Chest X-ray improvement&#xD;
&#xD;
        -  Duration of hospitalization&#xD;
&#xD;
        -  All cause mortality&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 16, 2020</start_date>
  <completion_date type="Actual">November 20, 2020</completion_date>
  <primary_completion_date type="Actual">October 30, 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>
    <intervention_model_description>Randomized, Double-Blind, Placebo-Controlled Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Virological clearance</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>• Presence of virus will be negative on Day 7 detected by RT PCR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Remission of fever</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>• Body temperature will be &lt; 37.5 C by day 7 detected by Infrared thermometer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Remission of cough</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>• Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patients requiring oxygen</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>Detected SPO2 level &lt;94% on Day 7or before by pulse oxymeter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients failing to maintain SpO2 &gt;93% despite oxygenation</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>Patients who fail to maintain pulse oxymeter detected SpO2 level&gt;93% despite O2 supplementation of 2-6 L/min, on Day 7 or before</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days on oxygen support</measure>
    <time_frame>within 7 days after enrollment</time_frame>
    <description>Any number of days on oxygen support on Day 7 or before recorded in CRF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization</measure>
    <time_frame>within 14 days after enrollment</time_frame>
    <description>Hospital stay ≥7days to ≤14 days as per CRF records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All causes of mortality</measure>
    <time_frame>within 14 days after enrollment</time_frame>
    <description>Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>COVID-19 Patients</condition>
  <arm_group>
    <arm_group_label>Tab Ivermectin +Cap Doxycycline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5)&#xD;
+ Placebo one tablet D2-5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tab Ivermectin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5&#xD;
+ Placebo two tablets D1 followed by Placebo one tablet D2-5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug: Placebo&#xD;
3 Placebo tablets D1 followed by 2 tablets D2-5</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivermectin + Doxycycline + Placebo</intervention_name>
    <description>Arm I: 200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5)&#xD;
Placebo one tablet D2-5</description>
    <arm_group_label>Tab Ivermectin +Cap Doxycycline</arm_group_label>
    <other_name>Tab IVERA +Cap Doxycycline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivermectin + Placebo</intervention_name>
    <description>Arm II: Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5 + Placebo two tablets D1 followed by Placebo one tablet D2-5</description>
    <arm_group_label>Tab Ivermectin</arm_group_label>
    <other_name>Tab IVERA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Arm III: 3 Placebo tablets D1 followed by 2 tablets D2-5</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Tab Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criterion:&#xD;
&#xD;
          -  Bangladeshi aged 18-65 years admitted to any of the aforementioned study sites&#xD;
             (hospitals)&#xD;
&#xD;
          -  Either sex&#xD;
&#xD;
          -  At the enrollment having at least one of the following symptoms: Temp 37.5 C or above,&#xD;
             Cough, Sore throat&#xD;
&#xD;
          -  SpO2 &gt;94%&#xD;
&#xD;
          -  Duration of illness ≤ 7 days&#xD;
&#xD;
          -  No oxygen support on enrollment&#xD;
&#xD;
          -  Capable of swallowing oral medication&#xD;
&#xD;
          -  PCR positive for SARS-CoV2 virus&#xD;
&#xD;
          -  The participant properly informed about the study and agreed to sign the informed&#xD;
             consent form (ICF)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to ivermectin or doxycycline; or other contraindications to any of the study&#xD;
             medications&#xD;
&#xD;
          -  History of chronic heart disease (IHD, heart failure, documented cardiomyopathy etc)&#xD;
&#xD;
          -  History of chronic liver disease (SGPT value more than 3 times of normal value)&#xD;
&#xD;
          -  History of chronic kidney disease (S. Creatinine for male &gt;1.3 mg/dL or &gt;115 µmol/L&#xD;
             and for female &gt;1.2 mg/dL or &gt;106.1 µmol/L)&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Participated in any other clinical trial within last 4 weeks&#xD;
&#xD;
          -  H/o received Ivermectin/Doxycycline within last 7 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wasif Ali Khan, MBBS, MHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Centre for Diarrhoeal Disease Research, Bangladesh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icddr,B</name>
      <address>
        <city>Dhaka</city>
        <zip>1000</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 17, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>February 1, 2021</last_update_submitted>
  <last_update_submitted_qc>February 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</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>Doxycycline</mesh_term>
    <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/NCT04407130
org study id: PR-20039
nct id: NCT04407130
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Burden:

      Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in
      early December 2019.Presently known to be caused by a novel beta-corona virus, named as
      Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2).

      World Health Organization (WHO) declared a pandemic on March.

      The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea
      and pneumonia

      Infected individuals exhibit:

        1. Mostly mild illness (80% +) recover without any treatment (~80%)

        2. Moderate illness that needs hospitalization and recovers after standard

        3. supportive treatment (~14%)

        4. Critical illness (~5%) needs ICU support

        5. Death (1-2% )

      COVID-19 has now spread >210 countries and territories globally. SARS-CoV-2 is a respiratory
      virus which spreads primarily through droplets generalized when an infected person coughs or
      sneezes or through droplets of saliva or discharge from the nose.

      Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be
      more common in older individuals and those with co-morbidities, such as chronic lung disease,
      cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at
      risk for critical illness including multi-organ failure and death. Seen more in Bangladesh
      between 21-40 yrs of age.

      Knowledge Gap:

      There is no specific treatment against this new virus that WHO has officially declared until
      now.There are many pharmacologic therapies that are being used or considered for treatment of
      COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19):
      V 5.0 date 9th April 2020) CDC, DGHS, GoB

      Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in
      COVID-19 patients from other countries as well as its availability & affordability of those
      repurposed medicines
Objectives:

      General Objective:

      The aim of the study is to evaluate efficacy and safety of ivermectin in combination with
      doxycycline or ivermectin alone for the treatment of hospitalized SARS-CoV-2 infected adult
      Bangladeshi COVID-19 +ve patients and to compare with placebo; where all three arms will
      receive the standard care of treatment of COVID-19 infected patients in the hospital. By
      successful demonstration of the safety and efficacy of these repurposed medicines, it may
      have the potential to play an important role in the treatment of COVID-19+ve patients.

      Specific Objective:

        1. Duration of the virological clearance rate

        2. Days required for remission of fever and cough

      Secondary Objective:

        -  Patients requiring oxygen

        -  Patients failing to maintain SpO2 >88 despite oxygenation

        -  Number of days on oxygen support

        -  Chest X-ray improvement

        -  Duration of hospitalization

        -  All cause mortality
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, Double-Blind, Placebo-Controlled Trial
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Virological clearance
time frame: within 7 days after enrollment
description: • Presence of virus will be negative on Day 7 detected by RT PCR
measure: Remission of fever
time frame: within 7 days after enrollment
description: • Body temperature will be < 37.5 C by day 7 detected by Infrared thermometer
measure: Remission of cough
time frame: within 7 days after enrollment
description: • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7
measure: Patients requiring oxygen
time frame: within 7 days after enrollment
description: Detected SPO2 level <94% on Day 7or before by pulse oxymeter
measure: Patients failing to maintain SpO2 >93% despite oxygenation
time frame: within 7 days after enrollment
description: Patients who fail to maintain pulse oxymeter detected SpO2 level>93% despite O2 supplementation of 2-6 L/min, on Day 7 or before
measure: Number of days on oxygen support
time frame: within 7 days after enrollment
description: Any number of days on oxygen support on Day 7 or before recorded in CRF
measure: Duration of hospitalization
time frame: within 14 days after enrollment
description: Hospital stay ≥7days to ≤14 days as per CRF records
measure: All causes of mortality
time frame: within 14 days after enrollment
description: Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate
arm group label: Tab Ivermectin +Cap Doxycycline
arm group type: Active Comparator
description: 200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5)
+ Placebo one tablet D2-5
arm group label: Tab Ivermectin
arm group type: Active Comparator
description: Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5
+ Placebo two tablets D1 followed by Placebo one tablet D2-5
arm group label: Placebo
arm group type: Placebo Comparator
description: Drug: Placebo
3 Placebo tablets D1 followed by 2 tablets D2-5
intervention type: Drug
intervention name: Ivermectin + Doxycycline + Placebo
description: Arm I: 200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5)
Placebo one tablet D2-5
arm group label: Tab Ivermectin +Cap Doxycycline
other name: Tab IVERA +Cap Doxycycline
intervention type: Drug
intervention name: Ivermectin + Placebo
description: Arm II: Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5 + Placebo two tablets D1 followed by Placebo one tablet D2-5
arm group label: Tab Ivermectin
other name: Tab IVERA
intervention type: Drug
intervention name: Placebo
description: Arm III: 3 Placebo tablets D1 followed by 2 tablets D2-5
arm group label: Placebo
other name: Tab Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Wasif Ali Khan, MBBS, MHS
role: Principal Investigator
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
facility: 
country: Bangladesh
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Doxycycline
mesh term: Ivermectin
sharing ipd: No