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

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT04409873

Collaborator

Rowpar Pharmaceuticals, Inc. (Industry)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

8.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 SARS-CoV 2 Severe Acute Respiratory Syndrome Coronavirus 2 Virus Disease Coronavirus Infections Pharyngeal Diseases	Drug: Oral-B Mouth Sore mouthwash Drug: Crest Pro-Health Multi-Protection mouthwash Drug: CloSYS Ultra Sensitive Rinse mouthwash Drug: Distilled water Drug: Listerine Zero Mouthwash Product	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A blinded randomized controlled parallel group design trialA 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

Official Title:

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

Actual Study Start Date :

Mar 31, 2021

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control (Distilled Water) Over the counter: Distilled water	Drug: Distilled water Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks. Other Names: water H2O
Experimental: Oral-B Mouth Sore (H2O2) mouthwash Over the counter: Oral-B Mouth Sore (Oral-B, USA) contains hydrogen peroxide (H2O2)	Drug: Oral-B Mouth Sore mouthwash Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks. Other Names: hydrogen peroxide H2O2
Experimental: Crest Pro-Health Multi-Protection (C21H38ClN) mouthwash Over the counter: Crest Pro-Health Multi-Protection (Crest, USA) contains cetylpyridinium chloride (C21H38ClN)	Drug: Crest Pro-Health Multi-Protection mouthwash Rinse and gargle 4 times daily, for 60 seconds, for 4 weeks. Other Names: cetylpyridinium chloride C21H38ClN
Experimental: CloSYS (ClO2) mouthwash Over the counter: CloSYS Ultra Sensitive Rinse (Rowpar Pharmaceutical Inc., USA) contains stabilized chlorine dioxide (ClO2)	Drug: CloSYS Ultra Sensitive Rinse mouthwash Rinse and gargle 4 times daily, for 45 seconds, for 4 weeks. Other Names: chlorine dioxide ClO2
Experimental: Listerine 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 30 seconds, for 4 weeks. Other Names: alcohol-free

Outcome Measures

Primary Outcome Measures

Change in SARS-Cov-2 viral load [Baseline to 4 weeks]
Change in saliva wash RT-PCR SARS-Cov-2 viral load

Secondary Outcome Measures

Change in self-reported clinical symptom onset [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 [Baseline to 4 weeks]
Change in healthcare utilization and hospitalization

Other Outcome Measures

Change in SARS-Cov-2 viral load in tobacco users, marijuana smokers, or vapers [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 [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 [Baseline to 4 weeks]
Change in healthcare utilization and hospitalization in tobacco users, marijuana smokers, or vapers

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.