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

• ClinicalTrials.gov Identifier: NCT04409873
• Recruitment Status: Completed
• First Posted: June 1, 2020
• Last Update Posted: September 30, 2022
• Sponsor: University of California, San Francisco
• Collaborator: Rowpar Pharmaceuticals, Inc.
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: May 28, 2020
• First Posted Date: June 1, 2020
• Last Update Posted Date: September 30, 2022
• Actual Study Start Date: March 31, 2021
• Actual Primary Completion Date: September 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2020)

Change in SARS-Cov-2 viral load [ Time Frame: Baseline to 4 weeks ]

Change in saliva wash RT-PCR SARS-Cov-2 viral load

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 28, 2020)

• Change in self-reported clinical symptom onset [ Time Frame: Baseline to 4 weeks ]
  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.
• Change in healthcare utilization and hospitalization [ Time Frame: Baseline to 4 weeks ]
  Change in healthcare utilization and hospitalization

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 28, 2020)

• Change in SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers [ Time Frame: Baseline to 4 weeks ]
  Change in saliva wash RT-PCR SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers
• Change in self-reported clinical symptom onset in tobacco users, marijuana smokers, or vapers [ Time Frame: Baseline to 4 weeks ]
  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.
• Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers [ Time Frame: Baseline to 4 weeks ]
  Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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.

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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A blinded randomized controlled parallel group design trial

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.

Primary Purpose: Supportive Care

Condition

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

Intervention

• Drug: Oral-B Mouth Sore mouthwash
  Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
  Other Names:

  • hydrogen peroxide
  • H2O2
• Drug: Crest Pro-Health Multi-Protection mouthwash
  Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
  Other Names:

  • cetylpyridinium chloride
  • C21H38ClN
• Drug: CloSYS Ultra Sensitive Rinse mouthwash
  Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.
  Other Names:

  • chlorine dioxide
  • ClO2
• Drug: Distilled water
  Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
  Other Names:

  • water
  • H2O
• Drug: Listerine Zero Mouthwash Product
  Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.
  Other Name: alcohol-free

Study Arms

• Placebo Comparator: Control (Distilled Water)
  Over the counter: Distilled water
  Intervention: Drug: Distilled water
• Experimental: Oral-B Mouth Sore (H2O2) mouthwash
  Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)
  Intervention: Drug: Oral-B Mouth Sore mouthwash
• Experimental: Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash
  Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)
  Intervention: Drug: Crest Pro-Health Multi-Protection mouthwash
• Experimental: CloSYS (ClO2) mouthwash
  Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)
  Intervention: Drug: CloSYS Ultra Sensitive Rinse mouthwash
• Experimental: Listerine Mouthwash
  Over the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)
  Intervention: Drug: Listerine Zero Mouthwash Product

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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 28, 2022): 54
• Original Estimated Enrollment (submitted: May 28, 2020): 120
• Actual Study Completion Date: September 10, 2022
• Actual Primary Completion Date: September 10, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04409873
• Other Study ID Numbers: 20-30874; R00RG2901 ( Other Grant/Funding Number: UCOP Emergency COVID19 Rsrch Fd: Cal Breast Cancer Rsrch Pgm )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: Rowpar Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Stuart A Gansky, DrPH; Professor and Lee Hysan Chair of Oral Epidemiology

• PRS Account: University of California, San Francisco
• Verification Date: September 2022