<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/NCT04409873</url>
  </required_header>
  <id_info>
    <org_study_id>20-30874</org_study_id>
    <secondary_id>R00RG2901</secondary_id>
    <nct_id>NCT04409873</nct_id>
  </id_info>
  <brief_title>Antiseptic Mouthwash / Pre-Procedural Rinse on SARS-CoV-2 Load (COVID-19)</brief_title>
  <acronym>AMPoL</acronym>
  <official_title>Effect of Antiseptic Mouthwash/Gargling Solutions and Pre-procedural Rinse on SARS-CoV-2 Load (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rowpar Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this pilot trial, 150 confirmed COVID-19 individuals will be randomly assigned to 1 of 5&#xD;
      groups: distilled water, CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA),&#xD;
      Oral-B Mouth Sore (Oral-B, USA), Crest Pro-Health Multi-Protection (Crest, USA), or Listerine&#xD;
      Zero (Johnson and Johnson, USA).&#xD;
&#xD;
      Study participants will be asked to rinse/gargle with 10-20ml (according to the rinse&#xD;
      instructions) of the assigned solutions 4 times per day, for 30-60 seconds, for 4 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SARS-CoV-2, the virus causing COVID-19, has affected vulnerable individuals, especially those&#xD;
      with comorbidities, and high exposure health care workers (HCWs). Typically, the virus first&#xD;
      colonizes in the upper respiratory tract (URT) causing clinical symptoms such as coughing,&#xD;
      sore throat, and then is transferred to the lower respiratory tract (LRT) which can lead to&#xD;
      severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and death, if it is not&#xD;
      managed.&#xD;
&#xD;
      The World Health Organization (WHO) has presented comprehensive guidelines underscoring&#xD;
      personal hygiene measures including respiratory hygiene against SARS, MERS, influenza, and&#xD;
      now SARS-CoV-2 / COVID-19. While personal protection equipment (PPE), personal hygiene&#xD;
      measures, environmental infection control, and physical distancing are crucial in mitigating&#xD;
      disease transmission, respiratory hygiene measures do not prevent SARS-CoV-2 colonization in&#xD;
      URTs and LRTs of infected individuals (symptomatic and asymptomatic).&#xD;
&#xD;
      Experimental and clinical research studies on infections similar to COVID-19 such as SARS,&#xD;
      MERS, and H5N1 have shown that using antiseptic mouthwash/gargling solutions, such as&#xD;
      products containing chlorhexidine gluconate (CHG), polyvinylpyrrolidone iodine (PVP-I),&#xD;
      chlorine dioxide (ClO2), cetylpyridinium chloride (CPC), and hydrogen peroxide (H2O2) can&#xD;
      reduce viral load. A randomized controlled trial (N=387) showed efficacy and&#xD;
      cost-effectiveness of gargling with water or a product containing PVP-I (3X/day, 20 seconds)&#xD;
      on URTIs in healthy volunteers (18-65 years) over 60 days from a societal perspective; in&#xD;
      vitro studies have shown that CloSYS, an over the counter mouthwash containing ClO2, was&#xD;
      effective on inactivating SARS-CoV as well as disinfecting dental unit waterlines, and&#xD;
      biofilm control in ultrasonic dental scaling units. A recent study has shown that CloSYS&#xD;
      Ultra Sensitive Oral Rinse reduced the viral load of SARS CoV 2, SARS CoV, and Influenza A&#xD;
      H3N2 to a varying extent. The data show that the viral load reduction of SARS CoV 2 by Ultra&#xD;
      Sensitive rinse was 10 fold more than the reduction of SARS CoV in 30s. Recently, the US&#xD;
      Centers for Disease Control (CDC) and the American Dental Association (ADA) have recommended&#xD;
      using a mouthwash containing 1.0-1.5% H2O2 as a pre-procedural rinse before dental treatment&#xD;
      to potentially reduce SARS-CoV-2 load; however, no in vivo clinical studies have been&#xD;
      conducted to support this claim.&#xD;
&#xD;
      The aim of this pilot trial is to evaluate the effect of four over-the-counter antiseptic&#xD;
      mouthwash/gargling solutions compared to a control (distilled water) to reduce SARS-CoV-2&#xD;
      load. In addition, study participants will be assessed for the severity of their clinical&#xD;
      symptoms during the study period. The 4-week protocol was selected as studies have shown that&#xD;
      patients can continue to shed the virus and potentially transmit it to the others for a 2 to&#xD;
      4 week period. An interim analysis is planned when 10 participants per arm (50 total)&#xD;
      complete the study using the alpha-spending function with O'Brien-Fleming boundary rule.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 31, 2021</start_date>
  <completion_date type="Actual">September 10, 2022</completion_date>
  <primary_completion_date type="Actual">September 10, 2022</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>A blinded randomized controlled parallel group design trial</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Study participants will be blinded to the solutions to the extent possible (i.e., similar packages with identification number bar codes).&#xD;
The lab technician who evaluates the SARS-CoV-2 load in samples will be blinded to the solutions and study groups.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in SARS-Cov-2 viral load</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in saliva wash RT-PCR SARS-Cov-2 viral load</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in self-reported clinical symptom onset</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in self-reported (questionnaire) clinical symptom onset. A symptom checklist will include: cough, runny nose, scratchy/sore throat, fever, chills, fatigue, muscle ache, shortness of breath, diarrhea/nausea/vomiting, loss of taste/smell, and red /painful eye.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in healthcare utilization and hospitalization</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in healthcare utilization and hospitalization</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in saliva wash RT-PCR SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in self-reported clinical symptom onset in tobacco users, marijuana smokers, or vapers</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in self-reported (questionnaire) clinical symptom onset in tobacco users, marijuana smokers, or vapers. A symptom checklist will include: cough, runny nose, scratchy/sore throat, fever, chills, fatigue, muscle ache, shortness of breath, diarrhea/nausea/vomiting, loss of taste/smell, and red /painful eye.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers</description>
  </other_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>COVID-19</condition>
  <condition>SARS-CoV 2</condition>
  <condition>Severe Acute Respiratory Syndrome Coronavirus 2</condition>
  <condition>Virus Disease</condition>
  <condition>Coronavirus Infections</condition>
  <condition>Pharyngeal Diseases</condition>
  <arm_group>
    <arm_group_label>Control (Distilled Water)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Over the counter: Distilled water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral-B Mouth Sore (H2O2) mouthwash</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CloSYS (ClO2) mouthwash</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Listerine Mouthwash</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral-B Mouth Sore mouthwash</intervention_name>
    <description>Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.</description>
    <arm_group_label>Oral-B Mouth Sore (H2O2) mouthwash</arm_group_label>
    <other_name>hydrogen peroxide</other_name>
    <other_name>H2O2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crest Pro-Health Multi-Protection mouthwash</intervention_name>
    <description>Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.</description>
    <arm_group_label>Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash</arm_group_label>
    <other_name>cetylpyridinium chloride</other_name>
    <other_name>C21H38ClN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CloSYS Ultra Sensitive Rinse mouthwash</intervention_name>
    <description>Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.</description>
    <arm_group_label>CloSYS (ClO2) mouthwash</arm_group_label>
    <other_name>chlorine dioxide</other_name>
    <other_name>ClO2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Distilled water</intervention_name>
    <description>Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.</description>
    <arm_group_label>Control (Distilled Water)</arm_group_label>
    <other_name>water</other_name>
    <other_name>H2O</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Listerine Zero Mouthwash Product</intervention_name>
    <description>Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.</description>
    <arm_group_label>Listerine Mouthwash</arm_group_label>
    <other_name>alcohol-free</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Tested positive for COVID-19 with a sample collected in the prior 7 days&#xD;
&#xD;
          -  Ability to read and speak English or Spanish&#xD;
&#xD;
          -  Ability to participate in the study for 4 weeks&#xD;
&#xD;
          -  Being asymptomatic or having mild or moderate symptoms (for example, sore throat,&#xD;
             coughing, fever, fatigue)&#xD;
&#xD;
          -  Ability to rinse/gargle&#xD;
&#xD;
          -  Not having any condition that might worsen with gargling solutions&#xD;
&#xD;
          -  Not having a history of mouthwash sensitivity&#xD;
&#xD;
          -  Not having an allergy to any mouthwash that has been used before&#xD;
&#xD;
          -  Not using another mouthwash/gargling solution since the most recent positive test&#xD;
&#xD;
          -  Not taking antimicrobial medications (antibacterial, antiviral, antibiotics including&#xD;
             off-label FDA-approved medications such as hydroxychloroquine)&#xD;
&#xD;
          -  Anticipated ability to participate in the study for 4 weeks&#xD;
&#xD;
          -  Have a cellphone and agree to receive text messages for reminders to use mouthwash&#xD;
             during the day and for follow-up visits, and can videoconference (like zoom) on a&#xD;
             cellphone, tablet, or computer for sample collection instructions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  People who because of their symptoms intend to receive antiviral medications that&#xD;
             could potentially affect viral load in their saliva samples&#xD;
&#xD;
          -  Pregnant or lactating women due to potential aversions to mouthwash solution&#xD;
             taste/smell.&#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>Stuart A Gansky, DrPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor and Lee Hysan Chair of Oral Epidemiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.</citation>
    <PMID>32091533</PMID>
  </reference>
  <reference>
    <citation>Meng L, Hua F, Bian Z. Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine. J Dent Res. 2020 May;99(5):481-487. doi: 10.1177/0022034520914246. Epub 2020 Mar 12.</citation>
    <PMID>32162995</PMID>
  </reference>
  <reference>
    <citation>Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection. J Dent Res. 2020 Jul;99(8):989. doi: 10.1177/0022034520918518. Epub 2020 Apr 9. No abstract available.</citation>
    <PMID>32271653</PMID>
  </reference>
  <reference>
    <citation>Reimer K, Wichelhaus TA, Schafer V, Rudolph P, Kramer A, Wutzler P, Ganzer D, Fleischer W. Antimicrobial effectiveness of povidone-iodine and consequences for new application areas. Dermatology. 2002;204 Suppl 1:114-20. doi: 10.1159/000057738.</citation>
    <PMID>12011534</PMID>
  </reference>
  <reference>
    <citation>Nagatake T, Ahmed K, Oishi K. Prevention of respiratory infections by povidone-iodine gargle. Dermatology. 2002;204 Suppl 1:32-6. doi: 10.1159/000057722.</citation>
    <PMID>12011518</PMID>
  </reference>
  <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>Sakai M, Shimbo T, Omata K, Takahashi Y, Satomura K, Kitamura T, Kawamura T, Baba H, Yoshihara M, Itoh H; Great Cold Investigators-I. Cost-effectiveness of gargling for the prevention of upper respiratory tract infections. BMC Health Serv Res. 2008 Dec 16;8:258. doi: 10.1186/1472-6963-8-258.</citation>
    <PMID>19087312</PMID>
  </reference>
  <reference>
    <citation>Wang WK, Chen SY, Liu IJ, Chen YC, Chen HL, Yang CF, Chen PJ, Yeh SH, Kao CL, Huang LM, Hsueh PR, Wang JT, Sheng WH, Fang CT, Hung CC, Hsieh SM, Su CP, Chiang WC, Yang JY, Lin JH, Hsieh SC, Hu HP, Chiang YP, Wang JT, Yang PC, Chang SC; SARS Research Group of the National Taiwan University/National Taiwan University Hospital. Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis. 2004 Jul;10(7):1213-9. doi: 10.3201/eid1007.031113.</citation>
    <PMID>15324540</PMID>
  </reference>
  <reference>
    <citation>Watamoto T, Egusa H, Sawase T, Yatani H. Clinical evaluation of chlorine dioxide for disinfection of dental instruments. Int J Prosthodont. 2013 Nov-Dec;26(6):541-4. doi: 10.11607/ijp.3465.</citation>
    <PMID>24179967</PMID>
  </reference>
  <reference>
    <citation>Wirthlin MR, Choi JH, Kye SB. Use of chlorine dioxide mouthrinse as the ultrasonic scaling lavage reduces the viable bacteria in the generated aerosols. J West Soc Periodontol Periodontal Abstr. 2006;54(2):35-44. No abstract available.</citation>
    <PMID>17214015</PMID>
  </reference>
  <reference>
    <citation>Chen C, Zhang XJ, Wang Y, Zhu LX, Liu J. Waste water disinfection during SARS epidemic for microbiological and toxicological control. Biomed Environ Sci. 2006 Jun;19(3):173-8.</citation>
    <PMID>16944772</PMID>
  </reference>
  <reference>
    <citation>Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020 Mar 3;12(1):9. doi: 10.1038/s41368-020-0075-9.</citation>
    <PMID>32127517</PMID>
  </reference>
  <reference>
    <citation>Meister TL, Bruggemann Y, Todt D, Conzelmann C, Muller JA, Gross R, Munch J, Krawczyk A, Steinmann J, Steinmann J, Pfaender S, Steinmann E. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020 Sep 14;222(8):1289-1292. doi: 10.1093/infdis/jiaa471. Erratum In: J Infect Dis. 2021 Feb 13;223(3):541.</citation>
    <PMID>32726430</PMID>
  </reference>
  <reference>
    <citation>Shewale JG, Ratcliff JL. Overinterpretation of the antiviral results for human coronavirus strain 229E (HCoV-229E) relative to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2021 Apr;93(4):1900-1902. doi: 10.1002/jmv.26722. Epub 2021 Jan 5. No abstract available.</citation>
    <PMID>33368396</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 28, 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>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anti-Infective Agents, Local</keyword>
  <keyword>Mouthwashes</keyword>
  <keyword>Gargle</keyword>
  <keyword>Saliva</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Pharyngeal Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrogen Peroxide</mesh_term>
    <mesh_term>Listerine</mesh_term>
    <mesh_term>Cetylpyridinium</mesh_term>
    <mesh_term>Chlorine dioxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 8, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04409873
org study id: 20-30874
secondary id: R00RG2901
nct id: NCT04409873
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
In this pilot trial, 150 confirmed COVID-19 individuals will be randomly assigned to 1 of 5
      groups: distilled water, CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA),
      Oral-B Mouth Sore (Oral-B, USA), Crest Pro-Health Multi-Protection (Crest, USA), or Listerine
      Zero (Johnson and Johnson, USA).

      Study participants will be asked to rinse/gargle with 10-20ml (according to the rinse
      instructions) of the assigned solutions 4 times per day, for 30-60 seconds, for 4 weeks.
SARS-CoV-2, the virus causing COVID-19, has affected vulnerable individuals, especially those
      with comorbidities, and high exposure health care workers (HCWs). Typically, the virus first
      colonizes in the upper respiratory tract (URT) causing clinical symptoms such as coughing,
      sore throat, and then is transferred to the lower respiratory tract (LRT) which can lead to
      severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and death, if it is not
      managed.

      The World Health Organization (WHO) has presented comprehensive guidelines underscoring
      personal hygiene measures including respiratory hygiene against SARS, MERS, influenza, and
      now SARS-CoV-2 / COVID-19. While personal protection equipment (PPE), personal hygiene
      measures, environmental infection control, and physical distancing are crucial in mitigating
      disease transmission, respiratory hygiene measures do not prevent SARS-CoV-2 colonization in
      URTs and LRTs of infected individuals (symptomatic and asymptomatic).

      Experimental and clinical research studies on infections similar to COVID-19 such as SARS,
      MERS, and H5N1 have shown that using antiseptic mouthwash/gargling solutions, such as
      products containing chlorhexidine gluconate (CHG), polyvinylpyrrolidone iodine (PVP-I),
      chlorine dioxide (ClO2), cetylpyridinium chloride (CPC), and hydrogen peroxide (H2O2) can
      reduce viral load. A randomized controlled trial (N=387) showed efficacy and
      cost-effectiveness of gargling with water or a product containing PVP-I (3X/day, 20 seconds)
      on URTIs in healthy volunteers (18-65 years) over 60 days from a societal perspective; in
      vitro studies have shown that CloSYS, an over the counter mouthwash containing ClO2, was
      effective on inactivating SARS-CoV as well as disinfecting dental unit waterlines, and
      biofilm control in ultrasonic dental scaling units. A recent study has shown that CloSYS
      Ultra Sensitive Oral Rinse reduced the viral load of SARS CoV 2, SARS CoV, and Influenza A
      H3N2 to a varying extent. The data show that the viral load reduction of SARS CoV 2 by Ultra
      Sensitive rinse was 10 fold more than the reduction of SARS CoV in 30s. Recently, the US
      Centers for Disease Control (CDC) and the American Dental Association (ADA) have recommended
      using a mouthwash containing 1.0-1.5% H2O2 as a pre-procedural rinse before dental treatment
      to potentially reduce SARS-CoV-2 load; however, no in vivo clinical studies have been
      conducted to support this claim.

      The aim of this pilot trial is to evaluate the effect of four over-the-counter antiseptic
      mouthwash/gargling solutions compared to a control (distilled water) to reduce SARS-CoV-2
      load. In addition, study participants will be assessed for the severity of their clinical
      symptoms during the study period. The 4-week protocol was selected as studies have shown that
      patients can continue to shed the virus and potentially transmit it to the others for a 2 to
      4 week period. An interim analysis is planned when 10 participants per arm (50 total)
      complete the study using the alpha-spending function with O'Brien-Fleming boundary rule.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A blinded randomized controlled parallel group design trial
primary purpose: Supportive Care
masking: Double (Participant, Outcomes Assessor)
masking description: Study participants will be blinded to the solutions to the extent possible (i.e., similar packages with identification number bar codes).
The lab technician who evaluates the SARS-CoV-2 load in samples will be blinded to the solutions and study groups.
measure: Change in SARS-Cov-2 viral load
time frame: Baseline to 4 weeks
description: Change in saliva wash RT-PCR SARS-Cov-2 viral load
measure: Change in self-reported clinical symptom onset
time frame: Baseline to 4 weeks
description: Change in self-reported (questionnaire) clinical symptom onset. A symptom checklist will include: cough, runny nose, scratchy/sore throat, fever, chills, fatigue, muscle ache, shortness of breath, diarrhea/nausea/vomiting, loss of taste/smell, and red /painful eye.
measure: Change in healthcare utilization and hospitalization
time frame: Baseline to 4 weeks
description: Change in healthcare utilization and hospitalization
measure: Change in SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers
time frame: Baseline to 4 weeks
description: Change in saliva wash RT-PCR SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers
measure: Change in self-reported clinical symptom onset in tobacco users, marijuana smokers, or vapers
time frame: Baseline to 4 weeks
description: Change in self-reported (questionnaire) clinical symptom onset in tobacco users, marijuana smokers, or vapers. A symptom checklist will include: cough, runny nose, scratchy/sore throat, fever, chills, fatigue, muscle ache, shortness of breath, diarrhea/nausea/vomiting, loss of taste/smell, and red /painful eye.
measure: Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers
time frame: Baseline to 4 weeks
description: Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers
arm group label: Control (Distilled Water)
arm group type: Placebo Comparator
description: Over the counter: Distilled water
arm group label: Oral-B Mouth Sore (H2O2) mouthwash
arm group type: Experimental
description: Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)
arm group label: Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash
arm group type: Experimental
description: Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)
arm group label: CloSYS (ClO2) mouthwash
arm group type: Experimental
description: Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)
arm group label: Listerine Mouthwash
arm group type: Experimental
description: Over the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)
intervention type: Drug
intervention name: Oral-B Mouth Sore mouthwash
description: Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
arm group label: Oral-B Mouth Sore (H2O2) mouthwash
other name: hydrogen peroxide
other name: H2O2
intervention type: Drug
intervention name: Crest Pro-Health Multi-Protection mouthwash
description: Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
arm group label: Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash
other name: cetylpyridinium chloride
other name: C21H38ClN
intervention type: Drug
intervention name: CloSYS Ultra Sensitive Rinse mouthwash
description: Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.
arm group label: CloSYS (ClO2) mouthwash
other name: chlorine dioxide
other name: ClO2
intervention type: Drug
intervention name: Distilled water
description: Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
arm group label: Control (Distilled Water)
other name: water
other name: H2O
intervention type: Drug
intervention name: Listerine Zero Mouthwash Product
description: Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.
arm group label: Listerine Mouthwash
other name: alcohol-free
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stuart A Gansky, DrPH
role: Principal Investigator
affiliation: Professor and Lee Hysan Chair of Oral Epidemiology
facility: 
country: United States
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PMID: 32091533
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PMID: 32271653
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PMID: 12011534
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PMID: 12011518
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PMID: 29633177
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PMID: 19087312
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PMID: 15324540
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PMID: 24179967
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PMID: 17214015
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PMID: 33368396
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Virus Diseases
mesh term: Pharyngeal Diseases
mesh term: Hydrogen Peroxide
mesh term: Listerine
mesh term: Cetylpyridinium
mesh term: Chlorine dioxide
sharing ipd: No
submitted: September 8, 2023