Evaluation of the Efficacy of Mouth Rinses With Commercial Mouthwashes to Decrease SARS-CoV-2 Viral Load in Saliva
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 48
- Locations
- 4
- Primary Endpoint
- Effect of the four different mouthwashes on the change of SARS-Cov2 viral load in saliva
Study Overview
Brief Summary
As no curative treatment for SARS-CoV-2 is currently available, most public health measures to contain the pandemic are based on preventing the spread of the pathogen. The virus is transmitted by the respiratory route and by direct contact with contaminated surfaces and subsequent contact with nasal, oral or ocular mucosa. Although patients with symptomatic coronavirus disease 2019 (COVID-19) have been the main source of transmission, observations suggest that asymptomatic and incubating patients also have the ability to transmit SARS-CoV-2. Angiotensin II converting enzyme (ACE2) is the main cellular receptor for SARS-CoV-2, which interacts with the spike protein to facilitate its entry. ACE2 receptors are highly expressed in the oral cavity and present at high levels in oral epithelial cells. The mean expression of ACE2 was higher in the tongue compared to that in other oral tissues and it has been found to be higher in the minor salivary glands than in the lungs. These findings strongly suggest that the oral cavity and specifically the saliva may be a high-risk route for SARS-CoV-2 infection. Thus, strategies reducing salivary viral load could contribute to reduce the risk of transmission. Furthermore, studies using macaques as animal models have shown that SARS-CoV persists for two days in oral mucous membranes before its diffusion to the lower respiratory tract. This offers an interesting preventive and therapeutic window of opportunity for the control of this disease. For this reason, the use of mouthwashes with antiseptics that have virucidal activity can be a simple preventive strategy that could easily be applied both by infected patients before being examined by sanitary personnel and in the general population. This study is a multi-centered, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of three different mouthwashes (chlorhexidine 0,12%, chlorhexidine 0,2%, and Cymenol -ZnCl2) in the salivary viral load of SARS-CoV-2 measured by qPCR at three different timepoints. A fourth group of patients using a distilled water mouth rinse is used as a control. Viral particles per ml of saliva are quantified at baseline and 5, 15 and 60 minutes after a 1-minute mouth rinse with the antiseptic or water. The study aims to test whether any of these standard oral antiseptics appear to diminish viral load in saliva and could therefore be used as a strategy to reduce transmission risk in clinical and social settings.
Detailed Description
Strategies reducing salivary viral load could contribute to reduce the risk of transmission of SARS-CoV-2. Thus, the use of mouthwashes with antiseptics that have virucidal activity can be a simple and low-cost preventive strategy that could easily be applied in the general population. To evaluate the effect of several antiseptics to neutralize or reduce the SARS-CoV-2 viral load in vivo in saliva samples, a multicentre, randomized, blind, four-parallel-group, placebo-controlled trial has been designed.
The study will be performed in Madrid, in three different hospitals: Fundación Jiménez Díaz University Hospital (Madrid, Spain), Villalba University General Hospital (Madrid, Spain) and Infanta Elena University Hospital (Madrid, Spain).
Every patient included is previously diagnosed and hospitalized because of SARS-COV-2 infection, being admitted mainly for respiratory pathology. All of them will be adults (age >18 years) and provide their voluntary written or oral consent to participation according to the hospital's ethics committee recommendations.
After approval of consent, the hospital staff responsible for the interventions will consecutively assign each participant a code following the order from a previously randomly generated table. The code will consist of a patient number and a letter corresponding to one of the four study groups (A, B, C and D), that will be known to the clinical personnel but unknown to the laboratory personnel who will process samples and extract RNA, as well as to those that will analyse the data. In this way, participants will be randomly assigned to one of the four treatment groups and the blind will be achieved by using identical tubes with the same volume for both mouthwashes and placebo.
Every included patient is asked not to eat, drink anything but water, chew gum, smoke, brush their teeth, or use any mouthwash for one hour prior to sample collection. In addition, they are not allowed to drink for half an hour after the mouthwash and eat for the entire test.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
The hospital staff consecutively assigned each participant a code following the order from a previously randomly generated table.
The code were unknown to the personnel who processed the samples and to those that analyzed the data.
Participants were blinded by using identical tubes with the same volume for both mouthwashes and placebo.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Lower than 7 days from the positive SARS-COV-2 PCR test of a nasopharyngeal sample
- •Have the ability to donate saliva samples and perform mouthwash
Exclusion Criteria
- •Patient participation in a COVID-19 research study using experimental drugs,
- •Use of an antiseptic mouthwash for 48 h before the start of the study
- •Any known hypersensitivity or allergy to components of the mouthwashes.
Arms & Interventions
Chlorhexidine 0,20%
15 ml 0,20% Chlorhexidine, one minute rinse.
Intervention: Lacer Clorhexidine 0.20% Colutorio (Drug)
Chlorhexidine 0,12%
15 ml 0,12% Chlorhexidine, one minute rinse.
Intervention: Lacer Clorhexidina Colutorio (Drug)
Gingilacer Encias Delicadas
15 ml 0,10% cymenol + 0,10% zinc chloride, one minute rinse.
Intervention: Gingilacer Encías Delicadas Colutorio (Drug)
Distilled Water
15 ml Distilled Water, one minute rinse.
Intervention: Distilled water (Drug)
Outcomes
Primary Outcomes
Effect of the four different mouthwashes on the change of SARS-Cov2 viral load in saliva
Time Frame: Minute 0 (before mouthwash) - Minute 5 (after mouthwash) - Minute 15 (after mouthwash) - Minute 60 (after mouthwash)
Determine the changes on the SARS-Cov2 viral load in saliva tested in vivo by RT-qPCR, between baseline values and those obtained at 5 minutes, at 15 minutes and at 60 minutes, after the use of four different mouthwashes randomized on 40 COVID-19 patients.
Effect of 4 different mouthwashes on the change of infective SARS-Cov2 viral load in saliva
Time Frame: Minute 0 (before mouthwash) - Minute 5 (after mouthwash) - Minute 15 (after mouthwash) - Minute 60 (after mouthwash)
Determine the changes on the SARS-Cov2 infective viral load in saliva tested in vivo by cell culture, between baseline values and those obtained at 5 minutes, at 15 minutes and at 60 minutes after the use of 4 different mouthwashes randomized on 40 COVID-19 patients.
Secondary Outcomes
No secondary outcomes reported
Investigators
Alejandro Mira Obrador
Chief investigator of the Oral Microbiome Lab
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana