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COVID-19Phase 2AMPoLNCT04409873

Antiseptic Mouthwash / Pre-Procedural Rinse on SARS-CoV-2 Load (COVID-19)

A Phase 2 study testing Oral-B Mouth Sore mouthwash, Crest Pro-Health Multi-Protection mouthwash and CloSYS Ultra Sensitive Rinse mouthwash in people with COVID-19 and SARS-CoV 2, run by University of California, San Francisco at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oral-B Mouth Sore mouthwash, Crest Pro-Health Multi-Protection mouthwash and CloSYS Ultra Sensitive Rinse mouthwash
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
1 siteUnited States
Study dates
31 Mar 2021to 10 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Tested positive for COVID-19 with a sample collected in the prior 7 days
  • Ability to read and speak English or Spanish
  • Ability to participate in the study for 4 weeks
  • Being asymptomatic or having mild or moderate symptoms (for example, sore throat, coughing, fever, fatigue)
  • Ability to rinse/gargle
  • Not having any condition that might worsen with gargling solutions
Show all 12Show fewer
  • Not having a history of mouthwash sensitivity
  • Not having an allergy to any mouthwash that has been used before
  • Not using another mouthwash/gargling solution since the most recent positive test
  • Not taking antimicrobial medications (antibacterial, antiviral, antibiotics including off-label FDA-approved medications such as hydroxychloroquine)
  • Anticipated ability to participate in the study for 4 weeks
  • Have a cellphone and agree to receive text messages for reminders to use mouthwash during the day and for follow-up visits, and can videoconference (like zoom) on a cellphone, tablet, or computer for sample collection instructions

Who cannot join

  • People who because of their symptoms intend to receive antiviral medications that could potentially affect viral load in their saliva samples
  • Pregnant or lactating women due to potential aversions to mouthwash solution taste/smell.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University Of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Effect of Antiseptic Mouthwash/Gargling Solutions and Pre-procedural Rinse on SARS-CoV-2 Load (COVID-19)

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.

Read the detailed description

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.

Being tested
Oral-B Mouth Sore mouthwash, Crest Pro-Health Multi-Protection mouthwash, CloSYS Ultra Sensitive Rinse mouthwash, Distilled water, Listerine Zero Mouthwash Product
Keywords
Anti-Infective Agents, Local, Mouthwashes, Gargle, Saliva
Medical subject headings
COVID-19, Virus Diseases, Coronavirus Infections, Pharyngeal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral-B Mouth Sore mouthwashDrug

    Also called hydrogen peroxide, H2O2

    Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.

  • Crest Pro-Health Multi-Protection mouthwashDrug

    Also called cetylpyridinium chloride, C21H38ClN

    Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.

  • CloSYS Ultra Sensitive Rinse mouthwashDrug

    Also called chlorine dioxide, ClO2

    Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.

  • Distilled waterDrug

    Also called water, H2O

    Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.

  • Listerine Zero Mouthwash ProductDrug

    Also called alcohol-free

    Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.

Study groups in NCT04409873
Study groupRoleWhat they receive
Control (Distilled Water)Placebo comparatorOver the counter: Distilled water
Receives: Drug: Distilled water
Oral-B Mouth Sore (H2O2) mouthwashExperimentalOver the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)
Receives: Drug: Oral-B Mouth Sore mouthwash
Crest Pro-Health Multi-Protection (C21H38ClN) mouthwashExperimentalOver the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)
Receives: Drug: Crest Pro-Health Multi-Protection mouthwash
CloSYS (ClO2) mouthwashExperimentalOver the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)
Receives: Drug: CloSYS Ultra Sensitive Rinse mouthwash
Listerine MouthwashExperimentalOver the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)
Receives: Drug: Listerine Zero Mouthwash Product

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in SARS-CoV-2 Viral Load

    The change in the outcome measure, SARS-CoV-2 viral load, in saliva wash RT-PCR was measured by Cycle Threshold (Ct) value. Ct value refers to the number of cycles it takes for the fluorescent signal generated during the PCR reaction to cross a certain threshold, indicating the presence of the target nucleic acid sequence, here, SARS-CoV-2. The lower the Ct value, the faster the threshold is crossed and the higher the viral load in a biological sample, suggesting a higher concentration of the SARS-CoV-2 virus in that sample.

    Measured: Baseline to 4 weeks

Secondary outcomes (2)

  1. Self-reported Clinical Symptom(s)

    Any self-reported (questionnaire) clinical symptom(s). A symptom checklist included 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. (Clinical symptoms were collected at baseline and at 3 months; only problems with the study mouth rinse were collected daily through 4 weeks.)

    Measured: Baseline to 3 months

  2. Any Hospitalization(s)

    Any hospitalization(s) from baseline to 4 weeks. Hospitalization(s) were collected on adverse event, unanticipated problem, and final disposition forms.

    Measured: Baseline to 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2020
  2. Study start31 Mar 2021
  3. Primary completion10 Sep 2022
  4. Study completion10 Sep 2022

Why it stopped: The funder decided not to continue funding, causing enrollment to cease prematurely and curtailing originally planned analyses. Participants with any samples collected after the baseline pre-rinse samples were included in the analysis.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
A blinded randomized controlled parallel group design trial
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04409873
Sponsor's protocol ID
20-30874
Other IDs
R00RG2901
Acronym
AMPoL
Status last verified
Oct 2023
First submitted
28 May 2020
Last updated
18 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32091533

  • 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.

    PubMed 32162995

  • 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.

    PubMed 32271653

  • 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.

    PubMed 12011534

  • 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.

    PubMed 12011518

  • 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.

    PubMed 29633177

  • 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.

    PubMed 19087312

  • 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.

    PubMed 15324540

  • 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.

    PubMed 24179967

  • 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.

    PubMed 17214015

  • 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.

    PubMed 16944772

  • 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.

    PubMed 32127517

  • 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.

    PubMed 32726430

  • 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.

    PubMed 33368396

  • Banava S, Radaic A, Kamarajan P, Cheng NF, Hernandez-Kapila YL, Gansky SA. Effect of Antiseptic Mouthwash/Gargling Solutions on SARS-CoV-2 Viral Load: A Randomized Clinical Trial. medRxiv [Preprint]. 2026 Jun 10:2026.05.20.26353686. doi: 10.64898/2026.05.20.26353686.

    PubMed 42238425

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral-B Mouth Sore mouthwash, Crest Pro-Health Multi-Protection mouthwash and CloSYS Ultra Sensitive Rinse mouthwash in people with COVID-19 and SARS-CoV 2, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in SARS-CoV-2 Viral Load (time frame: Baseline to 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04409873, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

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