Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients

NCT04707742 | Completed

• 1 other identifier: Interventional
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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 four different mouthwashes (CPC, chlorhexidine, povidone-iodine and H2O2) in the salivary viral load of SARS-CoV-2 measured by qPCR at three different timepoints. A fifth 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 30, 60 and 120 minutes after a 1-minute mouth rinse with the antiseptic or water. Our 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.

Conditions

Covid19

Keywords

COVID-19; MOUTHWASHES; SALIVA; VIRAL LOAD; ORAL; CLINICAL TRIAL

Outcome Measures

Primary Outcomes (2)

• Effect of 5 different mouthwashes on the SARS-Cov2 viral load.

  Determine the changes on the SARS-Cov2 viral load in saliva tested in vivo, between baseline values and those obtained at 30 minutes, at 60 minutes and at 120 minutes, after the use of 5 different mouthwashes randomized on 98 COVID-19 patients.

  Minute 0 (before mouthwash) - Minute 30 (after mouthwash) - Minute 60 (after mouthwash) - Minute 120 (after mouthwash)

• Effect of 5 different mouthwashes on the infective SARS-Cov2 viral load in saliva.

  Determine the changes on the SARS-Cov2 infective viral load in saliva tested in vivo, between baseline values and those obtained at 30 minutes and at 60 minutes after the use of 5 different mouthwashes randomized on 62 COVID-19 patients.

  Minute 0 (before mouthwash) - Minute 30 (after mouthwash) - Minute 60 (after mouthwash)

Study Arms (5)

Povidone-iodine 2% (Betadine© bucal 100 mg/ml)

EXPERIMENTAL

Povidone-iodine 2% (Betadine© bucal 100 mg/ml) (Mylan Pharmaceuticals, S.L., Spain). The concentration was adjusted to those previously indicated by diluting commercial formulas with distilled water minutes before rinsing (3 mL of povidone-iodine 10% for oral use - Betadine© with 12 mL of distilled water).

Drug: Betadine© bucal 100 mg/ml

Hydrogen peroxide 1% (Oximen® 3%)

EXPERIMENTAL

Hydrogen peroxide 1% (Oximen® 3%) (Reig Jofré, S.A., Spain). The concentration was adjusted to those previously indicated by diluting commercial formulas with distilled water minutes before rinsing (5 mL of hydrogen peroxide 3% - Oximen© with 10 mL of distilled water).

Drug: Oximen® 3%

Clorhexidine 0,12% (Clorhexidine Dental PHB©)

EXPERIMENTAL

Clorhexidine 0,12% (Clorhexidine Dental PHB©) contains clorhexidine (C22H30N10Cl2). Rinses were ready to use in their commercial formulas.

Drug: Clorhexidine Dental PHB©

Cetylpyridinium chloride 0,07% (Vitis Xtra Forte©)

EXPERIMENTAL

Cetylpyridinium chloride 0,07% (Vitis Xtra Forte©) contains cetylpyridinium chloride (C21H38ClN). Rinses were ready to use in their commercial formulas.

Drug: Vitis Xtra Forte©

Control (Distilled Water)

PLACEBO COMPARATOR

Distilled water.

Drug: Distilled Water

Interventions

Betadine© bucal 100 mg/ml DRUG

15 ml 2% povidone-iodine, one minute rinse.

Also known as: Povidone-iodine

Povidone-iodine 2% (Betadine© bucal 100 mg/ml)

Oximen® 3% DRUG

15 ml 1% hydrogen peroxide, one minute rinse.

Also known as: H2O2, Hydrogen peroxide

Hydrogen peroxide 1% (Oximen® 3%)

Clorhexidine Dental PHB© DRUG

15 ml 0,12% clorhexidine, one minute rinse.

Also known as: C22H30N10Cl2

Clorhexidine 0,12% (Clorhexidine Dental PHB©)

Vitis Xtra Forte© DRUG

15 ml 0,07% cetylpyridinium chloride, one minute rinse.

Also known as: C21H38ClN, Cetylpyridinium chloride

Cetylpyridinium chloride 0,07% (Vitis Xtra Forte©)

Distilled Water DRUG

15 ml distilled water, one minute rinse.

Also known as: H2O

Control (Distilled Water)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana: lead
• Hospital Universitario Fundación Jiménez Díaz: collaborator
• Hospital Universitario General de Villalba: collaborator
• Hospital Universitario Infanta Elena: collaborator
• Hospital Universitario Virgen de la Arrixaca: collaborator
• Hospital Clínico Universitario de Valencia: collaborator
• Dentaid SL: collaborator

Study Sites (1)

Alejandro Mira

Valencia, 46020, Spain

Location

Related Publications (2)

• Sanchez Barrueco A, Mateos-Moreno MV, Martinez-Beneyto Y, Garcia-Vazquez E, Campos Gonzalez A, Zapardiel Ferrero J, Bogoya Castano A, Alcala Rueda I, Villacampa Auba JM, Cenjor Espanol C, Moreno-Parrado L, Ausina-Marquez V, Garcia-Esteban S, Artacho A, Lopez-Labrador FX, Mira A, Ferrer MD. Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial. Emerg Microbes Infect. 2022 Dec;11(1):1833-1842. doi: 10.1080/22221751.2022.2098059.

  PMID: 35796097 DERIVED

• Ferrer MD, Barrueco AS, Martinez-Beneyto Y, Mateos-Moreno MV, Ausina-Marquez V, Garcia-Vazquez E, Puche-Torres M, Giner MJF, Gonzalez AC, Coello JMS, Rueda IA, Auba JMV, Espanol CC, Velasco AL, Abad DS, Garcia-Esteban S, Artacho A, Lopez-Labrador X, Mira A. Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2. Sci Rep. 2021 Dec 22;11(1):24392. doi: 10.1038/s41598-021-03461-y.

  PMID: 34937855 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Povidone-Iodine; Hydrogen Peroxide; Cetylpyridinium

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Iodophors; Iodine Compounds; Inorganic Chemicals; Polyvinyls; Vinyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Povidone; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Peroxides; Oxides; Anions; Ions; Electrolytes; Reactive Oxygen Species; Free Radicals; Oxygen Compounds; Pyridinium Compounds; Pyridines

Study Officials

• Alejandro Mira, PhD

  Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: BSc in Biological Sciences (Alicante University), MSc PhD (Oxford University), Senior Researcher (FISABIO Foundation)

Model Details: A multicentre, randomized, blind, five-parallel-group, placebo-controlled trial.

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 13, 2021
• Study Start: June 15, 2020
• Primary Completion: September 18, 2021
• Study Completion: September 30, 2021
• Last Updated: October 11, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)