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

NCT ID: NCT04409873

Last Updated: 2023-11-18

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-31

Study Completion Date

2022-09-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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COVID-19 SARS-CoV 2 Severe Acute Respiratory Syndrome Coronavirus 2 Virus Disease Coronavirus Infections Pharyngeal Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A blinded randomized controlled parallel group design trial
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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.

Study Groups

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Control (Distilled Water)

Over the counter: Distilled water

Group Type PLACEBO_COMPARATOR

Distilled water

Intervention Type DRUG

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

Oral-B Mouth Sore (H2O2) mouthwash

Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)

Group Type EXPERIMENTAL

Oral-B Mouth Sore mouthwash

Intervention Type DRUG

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

Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash

Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)

Group Type EXPERIMENTAL

Crest Pro-Health Multi-Protection mouthwash

Intervention Type DRUG

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

CloSYS (ClO2) mouthwash

Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)

Group Type EXPERIMENTAL

CloSYS Ultra Sensitive Rinse mouthwash

Intervention Type DRUG

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

Listerine Mouthwash

Over the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)

Group Type EXPERIMENTAL

Listerine Zero Mouthwash Product

Intervention Type DRUG

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

Interventions

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Oral-B Mouth Sore mouthwash

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

Intervention Type DRUG

Crest Pro-Health Multi-Protection mouthwash

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

Intervention Type DRUG

CloSYS Ultra Sensitive Rinse mouthwash

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

Intervention Type DRUG

Distilled water

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

Intervention Type DRUG

Listerine Zero Mouthwash Product

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

Intervention Type DRUG

Other Intervention Names

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hydrogen peroxide H2O2 cetylpyridinium chloride C21H38ClN chlorine dioxide ClO2 water H2O alcohol-free

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rowpar Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stuart A Gansky, DrPH

Role: PRINCIPAL_INVESTIGATOR

Professor and Lee Hysan Chair of Oral Epidemiology

Locations

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University Of California, San Francisco

San Francisco, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 32091533 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32162995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32271653 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12011534 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12011518 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29633177 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19087312 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15324540 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24179967 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17214015 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16944772 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32127517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32726430 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33368396 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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R00RG2901

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20-30874

Identifier Type: -

Identifier Source: org_study_id

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