<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/NCT04410159</url>
  </required_header>
  <id_info>
    <org_study_id>USIMalaysia</org_study_id>
    <nct_id>NCT04410159</nct_id>
  </id_info>
  <brief_title>Povidone-Iodine Vs Essential Oil Vs Tap Water Gargling For COVID-19 Patients</brief_title>
  <acronym>GARGLES</acronym>
  <official_title>A Pilot, Open-Labelled, Randomised Controlled Trial Of Povidone-Iodine Vs Essential Oil And Tap Water Gargling For COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universiti Sains Islam Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universiti Kebangsaan Malaysia Medical Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universiti Sains Islam Malaysia</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>
      The purpose of this study is to assess the ability of regular gargling to eliminate severe&#xD;
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the throat and nasopharynx. This 4&#xD;
      arms interventional study compares the effect of gargling using povidone-iodine, essential&#xD;
      oils- based, tap water with control (no intervention) among Stage 1 coronavirus disease-2019&#xD;
      (COVID-19) patients.&#xD;
&#xD;
      Findings from this study will provide new insight into the importance of gargling in the&#xD;
      treatment and prevention of COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Experimental plan&#xD;
&#xD;
      After consent is taken, all groups will be briefed regarding the study protocol separately.&#xD;
&#xD;
        -  Group A will be briefed on the correct procedures of gargling with Betadine®. The&#xD;
           participants will be instructed to take 10ml of povidone-iodine (PVP-I), tilt their&#xD;
           heads backward and gargle for 30 seconds, three times per day for 7 days&#xD;
&#xD;
        -  Group B will be briefed on the correct technique of gargling with Listerine®. The&#xD;
           participants will be instructed to take 20ml of essential oils, tilt their heads&#xD;
           backward and gargle for 30 seconds, three times per day for 7 days&#xD;
&#xD;
        -  Group C will be briefed on the correct technique of gargling with hydrogen peroxide. The&#xD;
           participants will be instructed to take 10ml of hydrogen peroxide, tilt their heads&#xD;
           backward and gargle for 30 seconds, three times per day for 7 days&#xD;
&#xD;
        -  Group D will be briefed about the involvement in this study. They will be managed&#xD;
           according to the standard protocol of the hospital with no additional intervention.&#xD;
&#xD;
      Monitoring&#xD;
&#xD;
        1. Oropharyngeal and nasopharyngeal swabs will be taken on day 4, 6 of intervention, and&#xD;
           day 12 post-intervention. The swabs will be subjected to detection of SARS-CoV-2 by&#xD;
           real-time reverse transcriptase-polymerase chain reaction (rt RT-PCR).&#xD;
&#xD;
        2. Patients will be given a chart for them to record their gargling practice and symptoms&#xD;
           (if any) during the intervention period ( 7 days)&#xD;
&#xD;
        3. Clinical data collection sheet will be provided to attending clinicians. The required&#xD;
           information includes demographic data, daily vital signs, serial absolute lymphocytic&#xD;
           count, LDH, chest radiograph, and symptoms. Clinical monitoring will be done until day&#xD;
           14 of the intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 22, 2020</start_date>
  <completion_date type="Actual">July 6, 2020</completion_date>
  <primary_completion_date type="Actual">June 29, 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>4 arms&#xD;
Gargle with povidone-iodine&#xD;
Gargle with essential oils&#xD;
Gargle with tap water&#xD;
Control</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Early Viral Clearance</measure>
    <time_frame>Day 6</time_frame>
    <description>Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Negative RT-PCR Results</measure>
    <time_frame>Day 12</time_frame>
    <description>RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Progress to More Severe Disease</measure>
    <time_frame>Day 12</time_frame>
    <description>Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Abnormal Radiological Findings</measure>
    <time_frame>Day 0-14</time_frame>
    <description>abnormal chest x-ray or CT scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Abnormal Laboratory Findings</measure>
    <time_frame>Day 0-14</time_frame>
    <description>Abnormal absolute lymphocytic count Abnormal C-reactive protein</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Povidone-iodine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Essential Oils</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tap water</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This group will receive the standard treatment protocol without any additional intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Povidone-Iodine</intervention_name>
    <description>Gargle</description>
    <arm_group_label>Povidone-iodine</arm_group_label>
    <other_name>Betadine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Essential oils</intervention_name>
    <description>Gargle</description>
    <arm_group_label>Essential Oils</arm_group_label>
    <other_name>Listerine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tap water</intervention_name>
    <description>Gargle</description>
    <arm_group_label>Tap water</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. adult aged 18 years and above&#xD;
&#xD;
          2. able to understand instructions&#xD;
&#xD;
          3. Stage 1 COVID-19&#xD;
&#xD;
          4. &lt; 5 days of illness or diagnosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Less than 18 years old&#xD;
&#xD;
          2. Unable to understand instructions&#xD;
&#xD;
          3. Stage 2 &amp; 3 COVID-19&#xD;
&#xD;
          4. Respiratory symptoms or fever on admission&#xD;
&#xD;
          5. Abnormal chest radiograph or computed tomography (CT) findings on admission&#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>NURUL A MOHAMED</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universiti Sains Islam Malaysia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universiti Kebangsaan Malaysia Medical Centre</name>
      <address>
        <city>Bandar Tun Razak</city>
        <state>Wilayah Persekutuan Kuala Lumpur</state>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <reference>
    <citation>Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018 Jun;7(2):249-259. doi: 10.1007/s40121-018-0200-7. Epub 2018 Apr 9.</citation>
    <PMID>29633177</PMID>
  </reference>
  <reference>
    <citation>Eggers M. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther. 2019 Dec;8(4):581-593. doi: 10.1007/s40121-019-00260-x. Epub 2019 Aug 14. Erratum In: Infect Dis Ther. 2019 Aug 22;:</citation>
    <PMID>31414403</PMID>
  </reference>
  <reference>
    <citation>Dennison DK, Meredith GM, Shillitoe EJ, Caffesse RG. The antiviral spectrum of Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):442-8. doi: 10.1016/s1079-2104(05)80124-6.</citation>
    <PMID>7614202</PMID>
  </reference>
  <reference>
    <citation>Satomura K, Kitamura T, Kawamura T, Shimbo T, Watanabe M, Kamei M, Takano Y, Tamakoshi A; Great Cold Investigators-I. Prevention of upper respiratory tract infections by gargling: a randomized trial. Am J Prev Med. 2005 Nov;29(4):302-7. doi: 10.1016/j.amepre.2005.06.013.</citation>
    <PMID>16242593</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <results_first_submitted>July 8, 2020</results_first_submitted>
  <results_first_submitted_qc>July 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 21, 2020</results_first_posted>
  <last_update_submitted>July 17, 2020</last_update_submitted>
  <last_update_submitted_qc>July 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universiti Sains Islam Malaysia</investigator_affiliation>
    <investigator_full_name>NURUL AZMAWATI MOHAMED</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>gargle</keyword>
  <keyword>povidone-iodine</keyword>
  <keyword>essential oils</keyword>
  <keyword>tap water</keyword>
  <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>Povidone-Iodine</mesh_term>
    <mesh_term>Listerine</mesh_term>
    <mesh_term>Povidone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The participant data from the final research dataset used in the published manuscript will be shared upon reasonable request. The protocol and data analysis will be shared in clinicaltrial</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>September to December 2020</ipd_time_frame>
    <ipd_access_criteria>email to drnurul@usim.edu.my</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT04410159/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>All patients were recruited 2 to 3 days after date of diagnosis (nasophryngeal swab postive for SARS-C0V-2. All patients were asymptomatic and admitted to the hospital for observation</recruitment_details>
      <pre_assignment_details>No significant event occurred after enrollment</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Povidone-iodine</title>
          <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
        </group>
        <group group_id="P2">
          <title>Essential Oils</title>
          <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
        </group>
        <group group_id="P3">
          <title>Tap Water</title>
          <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
        </group>
        <group group_id="P4">
          <title>Control</title>
          <description>This group will receive the standard treatment protocol without any additional intervention</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Povidone-iodine</title>
          <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
        </group>
        <group group_id="B2">
          <title>Essential Oils</title>
          <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
        </group>
        <group group_id="B3">
          <title>Tap Water</title>
          <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
        </group>
        <group group_id="B4">
          <title>Control</title>
          <description>This group received the standard treatment protocol without any additional intervention</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.4" spread="7.44"/>
                    <measurement group_id="B2" value="34.4" spread="12.50"/>
                    <measurement group_id="B3" value="30.8" spread="3.77"/>
                    <measurement group_id="B4" value="24.8" spread="2.68"/>
                    <measurement group_id="B5" value="30.6" spread="7.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Malaysia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Early Viral Clearance</title>
        <description>Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart</description>
        <time_frame>Day 6</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Povidone-iodine</title>
            <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
          </group>
          <group group_id="O2">
            <title>Essential Oils</title>
            <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
          </group>
          <group group_id="O3">
            <title>Tap Water</title>
            <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
          </group>
          <group group_id="O4">
            <title>Control</title>
            <description>This group will receive the standard treatment protocol without any additional intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Early Viral Clearance</title>
          <description>Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Negative RT-PCR Results</title>
        <description>RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12</description>
        <time_frame>Day 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Povidone-iodine</title>
            <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
          </group>
          <group group_id="O2">
            <title>Essential Oils</title>
            <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
          </group>
          <group group_id="O3">
            <title>Tap Water</title>
            <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
          </group>
          <group group_id="O4">
            <title>Control</title>
            <description>This group will receive the standard treatment protocol without any additional intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Negative RT-PCR Results</title>
          <description>RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients That Progress to More Severe Disease</title>
        <description>Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation</description>
        <time_frame>Day 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Povidone-iodine</title>
            <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
          </group>
          <group group_id="O2">
            <title>Essential Oils</title>
            <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
          </group>
          <group group_id="O3">
            <title>Tap Water</title>
            <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
          </group>
          <group group_id="O4">
            <title>Control</title>
            <description>This group will receive the standard treatment protocol without any additional intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Progress to More Severe Disease</title>
          <description>Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Abnormal Radiological Findings</title>
        <description>abnormal chest x-ray or CT scan</description>
        <time_frame>Day 0-14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Povidone-iodine</title>
            <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
          </group>
          <group group_id="O2">
            <title>Essential Oils</title>
            <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
          </group>
          <group group_id="O3">
            <title>Tap Water</title>
            <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
          </group>
          <group group_id="O4">
            <title>Control</title>
            <description>This group will receive the standard treatment protocol without any additional intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Abnormal Radiological Findings</title>
          <description>abnormal chest x-ray or CT scan</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Abnormal Laboratory Findings</title>
        <description>Abnormal absolute lymphocytic count Abnormal C-reactive protein</description>
        <time_frame>Day 0-14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Povidone-iodine</title>
            <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
          </group>
          <group group_id="O2">
            <title>Essential Oils</title>
            <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
          </group>
          <group group_id="O3">
            <title>Tap Water</title>
            <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
          </group>
          <group group_id="O4">
            <title>Control</title>
            <description>This group will receive the standard treatment protocol without any additional intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Abnormal Laboratory Findings</title>
          <description>Abnormal absolute lymphocytic count Abnormal C-reactive protein</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from day 1 of intervention until day 14</time_frame>
      <desc>Similar to clinicaltrial.gov</desc>
      <group_list>
        <group group_id="E1">
          <title>Povidone-iodine</title>
          <description>gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days&#xD;
Povidone-Iodine: Gargle</description>
        </group>
        <group group_id="E2">
          <title>Essential Oils</title>
          <description>gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days&#xD;
Essential oils: Gargle</description>
        </group>
        <group group_id="E3">
          <title>Tap Water</title>
          <description>gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days&#xD;
Tap water: Gargle</description>
        </group>
        <group group_id="E4">
          <title>Control</title>
          <description>This group will receive the standard treatment protocol without any additional intervention</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Inadequate budget for laboratory test lead to small numbers of subjects analyzed</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>NURUL AZMAWATI MOHAMED</name_or_title>
      <organization>UNIVERSITI SAINS ISLAM MALAYSIA</organization>
      <phone>+603 42892400 ext 2417</phone>
      <email>drnurul@usim.edu.my</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04410159
org study id: USIMalaysia
nct id: NCT04410159
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to assess the ability of regular gargling to eliminate severe
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the throat and nasopharynx. This 4
      arms interventional study compares the effect of gargling using povidone-iodine, essential
      oils- based, tap water with control (no intervention) among Stage 1 coronavirus disease-2019
      (COVID-19) patients.

      Findings from this study will provide new insight into the importance of gargling in the
      treatment and prevention of COVID-19.
Experimental plan

      After consent is taken, all groups will be briefed regarding the study protocol separately.

        -  Group A will be briefed on the correct procedures of gargling with Betadine®. The
           participants will be instructed to take 10ml of povidone-iodine (PVP-I), tilt their
           heads backward and gargle for 30 seconds, three times per day for 7 days

        -  Group B will be briefed on the correct technique of gargling with Listerine®. The
           participants will be instructed to take 20ml of essential oils, tilt their heads
           backward and gargle for 30 seconds, three times per day for 7 days

        -  Group C will be briefed on the correct technique of gargling with hydrogen peroxide. The
           participants will be instructed to take 10ml of hydrogen peroxide, tilt their heads
           backward and gargle for 30 seconds, three times per day for 7 days

        -  Group D will be briefed about the involvement in this study. They will be managed
           according to the standard protocol of the hospital with no additional intervention.

      Monitoring

        1. Oropharyngeal and nasopharyngeal swabs will be taken on day 4, 6 of intervention, and
           day 12 post-intervention. The swabs will be subjected to detection of SARS-CoV-2 by
           real-time reverse transcriptase-polymerase chain reaction (rt RT-PCR).

        2. Patients will be given a chart for them to record their gargling practice and symptoms
           (if any) during the intervention period ( 7 days)

        3. Clinical data collection sheet will be provided to attending clinicians. The required
           information includes demographic data, daily vital signs, serial absolute lymphocytic
           count, LDH, chest radiograph, and symptoms. Clinical monitoring will be done until day
           14 of the intervention.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 4 arms
Gargle with povidone-iodine
Gargle with essential oils
Gargle with tap water
Control
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Early Viral Clearance
time frame: Day 6
description: Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart
measure: Number of Participants With Negative RT-PCR Results
time frame: Day 12
description: RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12
measure: Number of Patients That Progress to More Severe Disease
time frame: Day 12
description: Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation
measure: Number of Patients With Abnormal Radiological Findings
time frame: Day 0-14
description: abnormal chest x-ray or CT scan
measure: Number of Patients With Abnormal Laboratory Findings
time frame: Day 0-14
description: Abnormal absolute lymphocytic count Abnormal C-reactive protein
arm group label: Povidone-iodine
arm group type: Experimental
description: gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days
arm group label: Essential Oils
arm group type: Experimental
description: gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days
arm group label: Tap water
arm group type: Experimental
description: gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days
arm group label: Control
arm group type: No Intervention
description: This group will receive the standard treatment protocol without any additional intervention
intervention type: Drug
intervention name: Povidone-Iodine
description: Gargle
arm group label: Povidone-iodine
other name: Betadine
intervention type: Drug
intervention name: Essential oils
description: Gargle
arm group label: Essential Oils
other name: Listerine
intervention type: Other
intervention name: Tap water
description: Gargle
arm group label: Tap water
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: NURUL A MOHAMED
role: Principal Investigator
affiliation: Universiti Sains Islam Malaysia
facility: 
country: Malaysia
citation: Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018 Jun;7(2):249-259. doi: 10.1007/s40121-018-0200-7. Epub 2018 Apr 9.
PMID: 29633177
citation: Eggers M. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther. 2019 Dec;8(4):581-593. doi: 10.1007/s40121-019-00260-x. Epub 2019 Aug 14. Erratum In: Infect Dis Ther. 2019 Aug 22;:
PMID: 31414403
citation: Dennison DK, Meredith GM, Shillitoe EJ, Caffesse RG. The antiviral spectrum of Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):442-8. doi: 10.1016/s1079-2104(05)80124-6.
PMID: 7614202
citation: Satomura K, Kitamura T, Kawamura T, Shimbo T, Watanabe M, Kamei M, Takano Y, Tamakoshi A; Great Cold Investigators-I. Prevention of upper respiratory tract infections by gargling: a randomized trial. Am J Prev Med. 2005 Nov;29(4):302-7. doi: 10.1016/j.amepre.2005.06.013.
PMID: 16242593
responsible party type: Principal Investigator
investigator affiliation: Universiti Sains Islam Malaysia
investigator full name: NURUL AZMAWATI MOHAMED
investigator title: Dr
mesh term: COVID-19
mesh term: Povidone-Iodine
mesh term: Listerine
mesh term: Povidone
sharing ipd: Yes
ipd description: The participant data from the final research dataset used in the published manuscript will be shared upon reasonable request. The protocol and data analysis will be shared in clinicaltrial
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: September to December 2020
ipd access criteria: email to drnurul@usim.edu.my
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Inadequate budget for laboratory test lead to small numbers of subjects analyzed
point of contact: 