Mouth Rinses for Inactivation of COVID-19

NCT04584684 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 20-2040
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, double-blind prospective trial to test the efficacy and acceptability of therapeutic, antiseptic mouth rinses to inactivate severe acute respiratory syndrome coronavirus (SARS-CoV-2) in saliva of COVID-19 positive patients aged 18-65 years old. All mouthrinses are commercially available and will be used according to on-label instructions. Patients will be randomized to a mouthrinse and will be asked to give a saliva sample immediately before and after a one minute mouthwash. Saliva samples will be collected from patients at 15 minute intervals thereafter up to an hour (15, 30, 45 and 60 minutes). The samples will be stored and used for real-time reverse transcription polymerase chain reaction (RT-PCR) detection of viral SARS-CoV-2 RNA and viral infectivity assays. Patients will also complete a short-survey on the taste and experience of using the mouthwash. This study involves 480 subject participants and one, 75-90 minute visit.

Conditions

Covid19; Coronavirus Infection; SARS-CoV-2 Infection

Keywords

Inactivation of COVID SARS-2 Virus; Antiseptic Mouth Rinses

Outcome Measures

Primary Outcomes (3)

• Change in Salivary Viral RNA Level of SARS-CoV-2

  Determination of SARS-CoV-2 viral RNA in COVID+ patient saliva using Quantitative Polymerase Chain Reaction (qPCR).

  Baseline, 30 minutes

• Change in Rapid Antigen Test Salivary Protein Levels of SARS-CoV-2

  Determination of SARS-CoV-2 protein antigen levels in COVID+ patient saliva using rapid antigen test as back-up if qPCR analysis is not possible. If the Rapid Antigen Test is needed and proves infeasible, an alternative test (i.e., sandwich ELISA) will be used.

  Baseline, 30 Minutes

• Change in Salivary Protein Antigen Levels of SARS-CoV-2

  Determination of SARS-CoV-2 protein antigen levels in COVID+ patient saliva using sandwich ELISA assay as back-up if qPCR analysis is not possible. If the sandwich ELISA assay proves infeasible, an alternative test (i.e., Rapid Antigen Test) will be used.

  Baseline, 30 minutes

Other Outcomes (2)

• Change in Salivary Viral Infectivity of SARS-CoV-2

  Baseline, 30 Minutes

• Participants' Willingness to Use Mouthrinse

  After using mouthrinse, between 0-minute and 15-minute saliva collection

Study Arms (6)

0.9% NaCl Saline

PLACEBO COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL of Saline.

Other: 0.9% w/v NaCL Saline

27% Ethanol plus essential oils

ACTIVE COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL 27% ethanol plus essential oils.

Drug: 27% Ethanol plus essential oils

0.075% Cetylpyridinium Chloride

ACTIVE COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL 0.075% Cetylpyridinium Chloride.

Drug: 0.075% Cetylpyridinium Chloride

1.5% w/v Hydrogen Peroxide

ACTIVE COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL of 1.5% w/v hydrogen peroxide rinse.

Drug: 1.5% w/v Hydrogen Peroxide

0.5% w/v Povidone-iodide

ACTIVE COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL .5% w/v povidone-iodide.

Drug: 0.5% w/v Povidone-iodide

0.12% Chlorhexidine Gluconate

ACTIVE COMPARATOR

Subject participants will rinse mouth one time for 60 seconds with 10 mL of 0.12% Chlorhexidine Gluconate.

Drug: 0.12% Chlorohexidine Gluconate

Interventions

0.9% w/v NaCL Saline OTHER

saline placebo rinse

0.9% NaCl Saline

1.5% w/v Hydrogen Peroxide DRUG

Over-the-counter antiseptic mouth rinse

1.5% w/v Hydrogen Peroxide

0.12% Chlorohexidine Gluconate DRUG

Dentist prescribed antimicrobial mouth rinse

0.12% Chlorhexidine Gluconate

27% Ethanol plus essential oils DRUG

Over-the-counter antiseptic mouth rinse

27% Ethanol plus essential oils

0.5% w/v Povidone-iodide DRUG

Over-the-counter antiseptic mouth rinse

0.5% w/v Povidone-iodide

0.075% Cetylpyridinium Chloride DRUG

Over-the-counter antiseptic mouth rinse

0.075% Cetylpyridinium Chloride

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed COVID+ status by physician. Either became symptomatic in the prior 7 days, or if not symptomatic, likely infected/exposed within the prior 7 days.
• Individuals (all sex, all gender) at least 18 years of age and at most 65 years of age and in good oral health without any known allergies to commercial dental products or cosmetics. American Society of Anesthesiologists (ASA) class I or II prior to COVID infection
• Evidence of a personally signed and dated informed consent document indicating the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial and all of their questions have been answered.
• Able to comprehend and follow the requirements of the study (including availability on scheduled visit dates) based on research site personnel's assessment.
• Females of childbearing potential will have a negative urine pregnancy test (on site) or be physically incapable of pregnancy (implants or injections, Intrauterine device, Bilateral tubal ligation, Hysterectomy, Ovariectomy, Women post-menopausal)

You may not qualify if:

• Patients who have been eating or drinking within an hour of the study
• Patients under 18 years old and older than 65 years old
• Subjects presenting with and/or self-reporting any of the following will not be included in the study:
• history of significant adverse effects following use of oral hygiene products such as toothpastes and mouthrinses. (self-reported)
• Self-reported allergy to iodine, ethanol, essential oils (Eucalyptol, Menthol, Methyl salicylate, Thymol), hydrogen peroxide, chlorhexidine gluconate, peroxyl, listerine, betadine, peridex, cetylpyridinium chloride, and other components in the mouth rinses (methyl salicylate, ethanol, saccharin sodium, glycerin, propylene glycol, sorbitol, Federal Food, Drug, and Cosmetic (FD\&C) blue no. 1, Poloxamer 407, Benzoic acid, Zinc chloride, Sodium benzoate, Sucralose, PolyEthylene Glycol - 40 (PEG-40) sorbitan diisostearate, potassium sorbate, citric acid).
• History of serious medical conditions that, at the discretion of the Investigator, will disqualify the subject. (Self-reported)
• A history of severe dry mouth (xerostomia), drug-induced xerostomia (antidepressants, anticonvulsants, antihypertensives), or Sjogren's syndrome
• A history of recent (within the last 30 days) or current recent oral herpes flare up, candida (thrush) infection, apthous ulcer flare up, current/active severe periodontal disease, or other recent oral viral infection or flare up within the past 30 days (self-reported)
• Current history of alcohol or drug abuse (self-reported).
• History of drinking water or eating food within an hour of the study visit.
• History of drinking alcohol within 12 hours of the study visit.
• History of using a commercial mouthrinse within 24 hours of the study visit.
• Participation in any study involving oral care products, concurrently or within the previous 30 days. (self-reported)
• Positive pregnancy test, reported pregnancy or lactation (this criterion is due to oral tissue changes related to pregnancy and nursing which can affect interpretation of study results. Additionally, women are advised to check with their physician before using Povidone-iodine during pregnancy and lactation, which cannot occur in a blinded, randomized trial.)
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this trial.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

General and Oral Health Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (17)

• State Officials Announce Latest COVID-19 Facts Including New Data on Racial Demographics and Expanded Health Care Worker Data. California Department of Public Health (2020).

  BACKGROUND

• Sorveglianza Integrata COVID-19 in Italia. Instituto Superiore di Sanitahttps://portale.fnomceo.it/wp-content/uploads/2020/04/Infografica_9aprile-ITA.pdf (2020).

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• Carrouel F, Conte MP, Fisher J, Goncalves LS, Dussart C, Llodra JC, Bourgeois D. COVID-19: A Recommendation to Examine the Effect of Mouthrinses with beta-Cyclodextrin Combined with Citrox in Preventing Infection and Progression. J Clin Med. 2020 Apr 15;9(4):1126. doi: 10.3390/jcm9041126.

  PMID: 32326426 BACKGROUND

• Dennison DK, Meredith GM, Shillitoe EJ, Caffesse RG. The antiviral spectrum of Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):442-8. doi: 10.1016/s1079-2104(05)80124-6.

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• Hasheminia D, Moaddabi A, Moradi S, Soltani P, Moannaei M, Issazadeh M. The efficacy of 1% Betadine mouthwash on the incidence of dry socket after mandibular third molar surgery. J Clin Exp Dent. 2018 May 1;10(5):e445-e449. doi: 10.4317/jced.54444. eCollection 2018 May.

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• Challacombe SJ, Kirk-Bayley J, Sunkaraneni VS, Combes J. Povidone iodine. Br Dent J. 2020 May;228(9):656-657. doi: 10.1038/s41415-020-1589-4. No abstract available.

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• Kirk-Bayley, J., Challacombe, S., Sunkaraneni, V. & Combes, J. The Use of Povidone Iodine Nasal Spray and Mouthwash During the Current COVID-19 Pandemic May Protect Healthcare Workers and Reduce Cross Infection. SSRN Electron. J.(2020) doi:10.2139/ssrn.3563092.

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MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Ethanol; Oils, Volatile; Cetylpyridinium

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Oils; Lipids; Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Laura Jacox, DMD, PhD, MS
• Organization: University of North Carolina at Chapel Hill

ljacox@live.unc.edu

847-702-0988

Study Officials

• Laura Jacox, DMD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blind prospective trial to test the efficacy and acceptability of 5 therapeutic, antiseptic mouth rinses to inactivate SARS-CoV-2 virus in saliva of COVID-19 positive patients.

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: October 14, 2020
• Study Start: December 18, 2020
• Primary Completion: October 21, 2021
• Study Completion: October 21, 2021
• Last Updated: March 25, 2024
• Results First Posted: March 25, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: following publication up to 1 year
• Access Criteria: Deidentified individual data that supports the results will be shared beginning following publication up to 1 year provided the investigator who proposes to use the data has approval from an IRB, IEC, or REB as applicable, and an executed data use/sharing agreement with UNC.

Locations

US (1)