A Phase 2 interventional study of Oral-B Mouth Sore mouthwash and Crest Pro-Health Multi-Protection mouthwash in COVID-19, SARS-CoV 2 and Severe Acute Respiratory Syndrome Coronavirus 2, sponsored by University of California, San Francisco. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-11-18.
Sponsored by University of California, San Francisco · Phase 2, Interventional, and Supportive care
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.
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 54 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Over the counter: Distilled water
Drug: Distilled water
Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)
Drug: Oral-B Mouth Sore mouthwash
Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)
Drug: Crest Pro-Health Multi-Protection mouthwash
Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)
Drug: CloSYS Ultra Sensitive Rinse mouthwash
Over the counter: Listerine Zero (Alcohol-Free)(Johnson and Johnson, USA) (C30H52O3)
Drug: Listerine Zero Mouthwash Product
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Also known as: hydrogen peroxide, H2O2
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Also known as: cetylpyridinium chloride, C21H38ClN
Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks.
Also known as: chlorine dioxide, ClO2
Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks.
Also known as: water, H2O
Rinse and gargle 4 times daily, for 30 seconds, for 4 weeks.
Also known as: alcohol-free
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.
Time frame: Baseline to 4 weeks
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.)
Time frame: Baseline to 3 months
Any Hospitalization(s)
Any hospitalization(s) from baseline to 4 weeks. Hospitalization(s) were collected on adverse event, unanticipated problem, and final disposition forms.
Time frame: Baseline to 4 weeks
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
Time frame: Baseline to 4 weeks
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.
Time frame: Baseline to 3 months
Any Hospitalization(s) in Tobacco Users, Marijuana Smokers, or Vapers
Any hospitalization(s) in tobacco users, marijuana smokers, or vapers during the study period
Time frame: Baseline to 4 weeks
In the initial recruitment phase, 54 participants signed the consent form and were assigned to one of five study groups. However, only 49 participants completed the entire 4-week study period.
| Milestone | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash |
|---|---|---|---|---|---|
| Started | 12 | 11 | 12 | 12 | 7 |
| Completed | 12 | 8 | 11 | 12 | 6 |
| Not completed | 0 | 3 | 1 | 0 | 1 |
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.
| Absolute Change in Cycle Threshold | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash |
|---|---|---|---|---|---|
| Change in SARS-CoV-2 Viral Load | -0.6 ± 1.9 | -0.4 ± 1.5 | 0.8 ± 1.4 | -0.4 ± 2.0 | -1.4 ± 0.8 |
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.)
| Participants | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash |
|---|---|---|---|---|---|
| Self-reported Clinical Symptom(s) | 1 | 0 | 0 | 0 | 0 |
Any hospitalization(s) from baseline to 4 weeks. Hospitalization(s) were collected on adverse event, unanticipated problem, and final disposition forms.
| Participants | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash |
|---|---|---|---|---|---|
| Any Hospitalization(s) | 0 | 0 | 0 | 0 | 0 |
Change in saliva wash RT-PCR SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Any hospitalization(s) in tobacco users, marijuana smokers, or vapers during the study period
No measurements were reported for this outcome.
Collected over Adverse event data were collected from baseline up to 12 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Control (Distilled Water) | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Oral-B Mouth Sore (H2O2) Mouthwash | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
| Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| CloSYS (ClO2) Mouthwash | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Listerine Mouthwash | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) |
| Event | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash |
|---|---|---|---|---|---|
| unanticipated eventProduct Issues | 0/12 | 0/11 | 0/12 | 0/12 | 1/7 |
| Age, Categorical(Participants) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| <=18 years | 0 | 1 | 0 | 0 | 0 | 1 |
| Between 18 and 65 years | 11 | 10 | 11 | 9 | 7 | 48 |
| >=65 years | 1 | 0 | 1 | 3 | 0 | 5 |
| Age, Continuous(Year) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| Mean | 38.0 ± 11.48 | 31.7 ± 8.65 | 45.6 ± 11.77 | 45.3 ± 17.30 | 37.3 ± 12.54 | 39.9 ± 13.40 |
| Sex: Female, Male(Participants) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| Female | 8 | 8 | 5 | 6 | 4 | 31 |
| Male | 4 | 3 | 7 | 6 | 3 | 23 |
| Ethnicity (NIH/OMB)(Participants) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 4 | 2 | 3 | 3 | 12 |
| Not Hispanic or Latino | 11 | 7 | 10 | 9 | 4 | 41 |
| Unknown or Not Reported | 1 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 4 | 1 | 2 | 2 | 0 | 9 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 1 | 0 | 0 | 1 |
| Black or African American | 0 | 2 | 1 | 0 | 0 | 3 |
| White | 7 | 4 | 6 | 6 | 5 | 28 |
| More than one race | 1 | 0 | 0 | 3 | 0 | 4 |
| Unknown or Not Reported | 0 | 4 | 2 | 1 | 2 | 9 |
| Region of Enrollment(participants) | Control (Distilled Water) | Oral-B Mouth Sore (H2O2) Mouthwash | Crest Pro-Health Multi-Protection (C21H38ClN) Mouthwash | CloSYS (ClO2) Mouthwash | Listerine Mouthwash | Total |
|---|---|---|---|---|---|---|
| United States | 12 | 11 | 12 | 12 | 7 | 54 |
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