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

COVID-19 Clinical Trial

— AMPoL  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04409873
• Other study ID #: 20-30874
• Secondary ID: R00RG2901
• Status: Terminated
• Phase: Phase 2
• Start date: March 31, 2021
• Est. completion date: September 10, 2022

Study information

• Verified date: October 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: September 10, 2022
• Est. primary completion date: September 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Oral-B Mouth Sore mouthwash
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
• Crest Pro-Health Multi-Protection mouthwash
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
• CloSYS Ultra Sensitive Rinse mouthwash
Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.
• Distilled water
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
• Listerine Zero Mouthwash Product
Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.

Locations

Country	Name	City	State
United States	University Of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Rowpar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in SARS-Cov-2 Viral Load in Tobacco Users, Marijuana Smokers, or Vapers	Change in saliva wash RT-PCR SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers	Baseline to 4 weeks
Other	Change in Self-reported Clinical Symptom Onset in Tobacco Users, Marijuana Smokers, or Vapers	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.	Baseline to 3 months
Other	Any Hospitalization(s) in Tobacco Users, Marijuana Smokers, or Vapers	Any hospitalization(s) in tobacco users, marijuana smokers, or vapers during the study period	Baseline to 4 weeks
Primary	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	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.)	Baseline to 3 months
Secondary	Any Hospitalization(s)	Any hospitalization(s) from baseline to 4 weeks. Hospitalization(s) were collected on adverse event, unanticipated problem, and final disposition forms.	Baseline to 4 weeks