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

NCT04409873 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20-30874R00RG2901
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

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

Keywords

Anti-Infective Agents, Local; Mouthwashes; Gargle; Saliva

Outcome Measures

Primary Outcomes (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.

  Baseline to 4 weeks

Secondary Outcomes (2)

• Self-reported Clinical Symptom(s)

  Baseline to 3 months

• Any Hospitalization(s)

  Baseline to 4 weeks

Other Outcomes (3)

• Change in SARS-Cov-2 Viral Load in Tobacco Users, Marijuana Smokers, or Vapers

  Baseline to 4 weeks

• Change in Self-reported Clinical Symptom Onset in Tobacco Users, Marijuana Smokers, or Vapers

  Baseline to 3 months

• Any Hospitalization(s) in Tobacco Users, Marijuana Smokers, or Vapers

  Baseline to 4 weeks

Study Arms (5)

Control (Distilled Water)

PLACEBO COMPARATOR

Over the counter: Distilled water

Drug: Distilled water

Oral-B Mouth Sore (H2O2) mouthwash

EXPERIMENTAL

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

Drug: Oral-B Mouth Sore mouthwash

Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash

EXPERIMENTAL

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

Drug: Crest Pro-Health Multi-Protection mouthwash

CloSYS (ClO2) mouthwash

EXPERIMENTAL

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

Drug: CloSYS Ultra Sensitive Rinse mouthwash

Listerine Mouthwash

EXPERIMENTAL

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

Drug: Listerine Zero Mouthwash Product

Interventions

Oral-B Mouth Sore mouthwash DRUG

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

Also known as: hydrogen peroxide, H2O2

Oral-B Mouth Sore (H2O2) mouthwash

Crest Pro-Health Multi-Protection mouthwash DRUG

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

Also known as: cetylpyridinium chloride, C21H38ClN

Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash

CloSYS Ultra Sensitive Rinse mouthwash DRUG

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

Also known as: chlorine dioxide, ClO2

CloSYS (ClO2) mouthwash

Distilled water DRUG

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

Also known as: water, H2O

Control (Distilled Water)

Listerine Zero Mouthwash Product DRUG

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

Also known as: alcohol-free

Listerine Mouthwash

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Rowpar Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University Of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (14)

• 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.

  PMID: 32091533 BACKGROUND

• 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.

  PMID: 32162995 BACKGROUND

• 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.

  PMID: 32271653 BACKGROUND

• 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.

  PMID: 12011534 BACKGROUND

• 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.

  PMID: 12011518 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 19087312 BACKGROUND

• 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.

  PMID: 15324540 BACKGROUND

• 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.

  PMID: 24179967 BACKGROUND

• 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.

  PMID: 17214015 BACKGROUND

• 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.

  PMID: 16944772 BACKGROUND

• 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.

  PMID: 32127517 BACKGROUND

• 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.

  PMID: 32726430 BACKGROUND

• 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.

  PMID: 33368396 BACKGROUND

MeSH Terms

Conditions

COVID-19; Virus Diseases; Coronavirus Infections; Pharyngeal Diseases

Interventions

Hydrogen Peroxide; Cetylpyridinium; chlorine dioxide; Water; Ethanol

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Peroxides; Oxides; Anions; Ions; Electrolytes; Inorganic Chemicals; Reactive Oxygen Species; Free Radicals; Oxygen Compounds; Organic Chemicals; Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxides; Alkalies; Alcohols

Limitations and Caveats

Study support was withdrawn by Funder, so enrollment ended, and only a priori planned interim analyses were performed.

Results Point of Contact

• Title: Dr. Stuart A. Gansky and Dr. Sepideh Banava
• Organization: University of California San Francisco

stuart.gansky@ucsf.edu ; sepideh.banava@ucsf.edu

415-502-8094; 415-630-0094

Study Officials

• Stuart A Gansky, DrPH

  Professor and Lee Hysan Chair of Oral Epidemiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A blinded randomized controlled parallel group design trial

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 1, 2020
• Study Start: March 31, 2021
• Primary Completion: September 10, 2022
• Study Completion: September 10, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)