The Efficacy of Pre-procedural Mouth Rinses on COVID-19 Saliva Viral Load

Study Overview
=================
Brief Summary
-----------------
Preoperative antiseptic mouth rinses have been widely used as a standard protocol before routine dental treatment reduces oral microorganism counts. During dental procedures, aerosolized microorganisms contaminate the dental environment and nearby surfaces and remain suspended for 4 hours. Thus, the reduction in the number of aerosolized microorganisms by pre-procedural rinsing may reduce cross-contamination between dentists, office personnel, and patients. Recent reviews have advocated the use of preoperative rinsing to control and reduce the risk of SARS-CoV-2 transmission. However, no clinical studies have been done yet to support the effectiveness of any pre-procedural oral rinses against SARS-CoV-2. The proposed study will mitigate the spread of COVID-19 disease in dental healthcare facilities and ensure the patients' good health and healthcare workers. The purpose of this clinical trial is to compare the efficacy of four commercially available mouth rinses povidone-iodine (PVP-I), hydrogen peroxide (H2O2), cetylpyridinium chloride (CPC), sodium hypochlorite (NaOCl) on the salivary SARS-CoV-2 viral load at four-time points (baseline and 5-, 30-, and 60-min post rinsing) relative to two control groups (distilled water and no-rinse) in a cohort of positive COVID-19 patients.

Detailed Description
-----------------
Saliva specimens will be collected from COVID-19-positive patients presenting to TETAMMAN clinics from January to March 2021. The total number of participants in this study will be 90 participants, with 15 per group (6 groups), and 4 saliva specimens from each patient in each group. A total of four mouth rinses and two control groups (distilled water and no-rinse). The studied mouth rinses were: 1% povidone-iodine (PVP-I) (Betadine Mouthwash/Gargle; Avrio Health LP, Stamford, CT, USA), 1.5% hydrogen peroxide (H2O2) (Peroxyl; Colgate-Palmolive, Guildford, UK), 0.075% cetylpyridinium chloride (CPC) (Colgate Total; Colgate-Palmolive, Guildford, UK), 80 ppm sodium hypochlorite (NaOCl) (Clinisept Dental Mouthwash; Clinical Health Technologies, Hinckley, Leicestershire, UK). Confirmed positive cases of COVID-19 will be recruited randomly at each TETAMMAN clinic based on inclusion and exclusion criteria to satisfy the total of 90 patients. Each participant will be introduced briefly to the study aims and then asked to sign a consent form. Demographic data and medical history will then be collected for each participant. The participants will be blinded to all mouth rinses, which will be labeled with identification codes, and presented in similar packages. Unstimulated saliva will be collected using the passive drool technique. Four saliva samples for each patient will be collected. The first saliva sample will be considered as a baseline sample that represents the baseline viral load. Then patients will be instructed to gargle the assigned mouth rinse gently, for 15 seconds. After that, the participants will spit the mouthwashes into a disposable plastic cup. After that, different salivary samples will be collected at 5 minutes, 30 minutes, and then 60 minutes. Thus, a total of four saliva samples will be gathered from each patient. The viral load will be measured by quantitative reverse transcription PCR.

Official Title
-----------------
Mouth Rinses Efficacy on Salivary SARS-CoV-2 Viral Load: A Randomized Clinical Trial

Conditions
-----------------
SARS-CoV-2, COVID-19, Mouthwashes, Viral Load, Polymerase Chain Reaction, Coronavirus, Covid19, Saliva

Intervention / Treatment
-----------------
* Drug: Distilled Water
* Drug: 1% Povidone Iodine (PVP-I)
* Drug: 1.5% Hydrogen Peroxide (H2O2)
* Drug: 0.075% Cetylpyridinium Chloride (CPC)
* Drug: 0.1% Sodium Hypochlorite
* Other: No rinse group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults age 18 years or older presented to TETAMMAN clinics, Jeddah, Saudi Arabia. COVID-19-positive patients confirmed by RT-PCR and within two days of oral or nasopharyngeal swabs Asymptomatic or within seven days of the onset of symptoms. Has the ability to rinse and expectorate. Exclusion Criteria: Participants who established antiviral, corticosteroid, antimicrobial, or immunosuppressive medications. Known allergy to one of the constituents of the mouth rinse Thyroid disease or on current radioactive iodine treatment Pregnant or breastfeeding women Lithium therapy History of radiotherapy or chemotherapy Use of mouthwash before presented to TETAMMAN clinics

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This randomizeda, single-center, randomized, double-blind, six-parallel-group, placebo-controlled trial compares the efficacy of four commercially available mouth rinses povidone-iodine (PVP-I), hydrogen peroxide (H2O2), cetylpyridinium chloride (CPC), sodium hypochlorite (NaOCl) on the salivary SARS-CoV-2 viral load at four-time points (baseline and 5-, 30-, and 60-min post rinsing) relative to two control groups (distilled water and no-rinse) in a cohort of positive COVID-19 patients.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Distilled Water<br>Vigorously rinse with 15 ml of the distilled water for 30 s (Water for Injections BP; Pharmaceutical Solutions Industry, Jeddah, SA) | Drug: Distilled Water<br>* Control group<br>* Other names: water (Water for Injections BP; Pharmaceutical Solutions Industry, Jeddah, SA);|
| Active Comparator: Povidone Iodine (PVP-I)<br>Vigorously rinse with 15 ml of the 1% povidone-iodine (PVP-I) (Betadine Mouthwash/Gargle; Avrio Health LP, Stamford, CT, USA) for 30 s | Drug: 1% Povidone Iodine (PVP-I)<br>* Over-the-counter antiseptic mouth rinse<br>* Other names: Betadine Mouthwash/Gargle; Avrio Health LP, Stamford, CT, USA;|
| Active Comparator: Hydrogen Peroxide (H2O2)<br>Vigorously rinse with 15 ml of the 1.5% hydrogen peroxide (H2O2) (Peroxyl; Colgate-Palmolive, Guildford, UK) for 30 s | Drug: 1.5% Hydrogen Peroxide (H2O2)<br>* Over-the-counter antiseptic mouth rinse<br>* Other names: Peroxyl; Colgate-Palmolive, Guildford, UK;|
| Active Comparator: Cetylpyridinium Chloride (CPC)<br>Vigorously rinse with 15 ml of the 0.075% cetylpyridinium chloride (CPC) (Colgate Total; Colgate-Palmolive, Guildford, UK) for 30 s | Drug: 0.075% Cetylpyridinium Chloride (CPC)<br>* Over-the-counter antiseptic mouth rinse<br>* Other names: Colgate Total; Colgate-Palmolive, Guildford, UK;|
| Active Comparator: Sodium Hypochlorite<br>Vigorously rinse with 15 ml of the 80 ppm sodium hypochlorite (NaOCl) (Clinisept Dental Mouthwash; Clinical Health Technologies, Hinckley, Leicestershire, UK) for 30 s | Drug: 0.1% Sodium Hypochlorite<br>* Over-the-counter antiseptic mouth rinse<br>* Other names: Clinisept Dental Mouthwash; Clinical Health Technologies, Hinckley, Leicestershire, UK;|
| Placebo Comparator: No rinse group<br>There is no mouth rinse in this group. Patients will collect the saliva at all 4-time points without gargling with the mouth rinse. | Other: No rinse group<br>* second control group<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the salivary viral load within each mouth rinse groups and controls | change in the salivary viral load overtime within each group will be measured by quantitative reverse transcription PCR (RT-qPCR) and expressed as copies/ml | Baseline (T0) vs 5 minutes (T1), baseline (T0) vs 30 minutes (T2), and baseline (T0) vs 60 minutes T3) | 
| Compare salivary viral load between mouth rinse groups and controls at baseline | Difference in Salivary viral load baseline value between the groups | Compare Baseline (T0) | 
| Compare salivary viral load between mouth rinse groups and controls at 5 minutes post rinsing | Difference in Salivary viral load baseline value between the groups | 5 minutes post rinsing (T1) | 
| Compare salivary viral load between mouth rinse groups and controls at 30 minutes post rinsing | Difference in Salivary viral load baseline value between the groups | 30 minutes post rinsing (T2) | 
| Compare salivary viral load between mouth rinse groups and controls at 60 minutes post rinsing | Difference in Salivary viral load baseline value between the groups | 60 minutes post rinsing (T3) |