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

NCT04721457 | Completed Phase 4 FDA Drug

• 1 other identifier: H-02-J-002; 1384
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV-2; Covid19; Mouthwashes; Viral Load; Polymerase Chain Reaction; Coronavirus; Saliva

Outcome Measures

Primary Outcomes (5)

• 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)

Study Arms (6)

Distilled Water

PLACEBO COMPARATOR

Vigorously rinse with 15 ml of the distilled water for 30 s (Water for Injections BP; Pharmaceutical Solutions Industry, Jeddah, SA)

Drug: Distilled Water

Povidone Iodine (PVP-I)

ACTIVE COMPARATOR

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)

Hydrogen Peroxide (H2O2)

ACTIVE COMPARATOR

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)

Cetylpyridinium Chloride (CPC)

ACTIVE COMPARATOR

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)

Sodium Hypochlorite

ACTIVE COMPARATOR

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

No rinse group

PLACEBO COMPARATOR

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

Interventions

Distilled Water DRUG

Control group

Also known as: water (Water for Injections BP; Pharmaceutical Solutions Industry, Jeddah, SA)

Distilled Water

1% Povidone Iodine (PVP-I) DRUG

Over-the-counter antiseptic mouth rinse

Also known as: Betadine Mouthwash/Gargle; Avrio Health LP, Stamford, CT, USA

Povidone Iodine (PVP-I)

1.5% Hydrogen Peroxide (H2O2) DRUG

Over-the-counter antiseptic mouth rinse

Also known as: Peroxyl; Colgate-Palmolive, Guildford, UK

Hydrogen Peroxide (H2O2)

0.075% Cetylpyridinium Chloride (CPC) DRUG

Over-the-counter antiseptic mouth rinse

Also known as: Colgate Total; Colgate-Palmolive, Guildford, UK

Cetylpyridinium Chloride (CPC)

0.1% Sodium Hypochlorite DRUG

Over-the-counter antiseptic mouth rinse

Also known as: Clinisept Dental Mouthwash; Clinical Health Technologies, Hinckley, Leicestershire, UK

Sodium Hypochlorite

No rinse group OTHER

second control group

No rinse group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• King Abdulaziz University: lead

Study Sites (1)

Alhamra TETAMMAN clinic (PHC)

Jeddah, Saudi Arabia

Location

Related Publications (17)

• To KK, Tsang OT, Yip CC, Chan KH, Wu TC, Chan JM, Leung WS, Chik TS, Choi CY, Kandamby DH, Lung DC, Tam AR, Poon RW, Fung AY, Hung IF, Cheng VC, Chan JF, Yuen KY. Consistent Detection of 2019 Novel Coronavirus in Saliva. Clin Infect Dis. 2020 Jul 28;71(15):841-843. doi: 10.1093/cid/ciaa149.

  PMID: 32047895 RESULT

• Ge ZY, Yang LM, Xia JJ, Fu XH, Zhang YZ. Possible aerosol transmission of COVID-19 and special precautions in dentistry. J Zhejiang Univ Sci B. 2020 May;21(5):361-368. doi: 10.1631/jzus.B2010010. Epub 2020 Mar 16.

  PMID: 32425001 RESULT

• Vergara-Buenaventura A, Castro-Ruiz C. Use of mouthwashes against COVID-19 in dentistry. Br J Oral Maxillofac Surg. 2020 Oct;58(8):924-927. doi: 10.1016/j.bjoms.2020.08.016. Epub 2020 Aug 15.

  PMID: 32859459 RESULT

• O'Donnell VB, Thomas D, Stanton R, Maillard JY, Murphy RC, Jones SA, Humphreys I, Wakelam MJO, Fegan C, Wise MP, Bosch A, Sattar SA. Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection. Function (Oxf). 2020;1(1):zqaa002. doi: 10.1093/function/zqaa002. Epub 2020 Jun 5.

  PMID: 33215159 RESULT

• 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 RESULT

• Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020 May 12;323(18):1843-1844. doi: 10.1001/jama.2020.3786.

  PMID: 32159775 RESULT

• Bruch MK. Toxicity and safety of topical sodium hypochlorite. Contrib Nephrol. 2007;154:24-38. doi: 10.1159/000096812.

  PMID: 17099299 RESULT

• De Nardo R, Chiappe V, Gomez M, Romanelli H, Slots J. Effects of 0.05% sodium hypochlorite oral rinse on supragingival biofilm and gingival inflammation. Int Dent J. 2012 Aug;62(4):208-12. doi: 10.1111/j.1875-595X.2011.00111.x. Epub 2012 May 11.

  PMID: 23017003 RESULT

• Seo HW, Seo JP, Cho Y, Ko E, Kim YJ, Jung G. Cetylpyridinium chloride interaction with the hepatitis B virus core protein inhibits capsid assembly. Virus Res. 2019 Apr 2;263:102-111. doi: 10.1016/j.virusres.2019.01.004. Epub 2019 Jan 9.

  PMID: 30639191 RESULT

• Feres M, Figueiredo LC, Faveri M, Stewart B, de Vizio W. The effectiveness of a preprocedural mouthrinse containing cetylpyridinium chloride in reducing bacteria in the dental office. J Am Dent Assoc. 2010 Apr;141(4):415-22. doi: 10.14219/jada.archive.2010.0193.

  PMID: 20354090 RESULT

• Marui VC, Souto MLS, Rovai ES, Romito GA, Chambrone L, Pannuti CM. Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: A systematic review. J Am Dent Assoc. 2019 Dec;150(12):1015-1026.e1. doi: 10.1016/j.adaj.2019.06.024.

  PMID: 31761015 RESULT

• Pitten FA, Kramer A. Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic. Arzneimittelforschung. 2001;51(7):588-95. doi: 10.1055/s-0031-1300084.

  PMID: 11505791 RESULT

• Osso D, Kanani N. Antiseptic mouth rinses: an update on comparative effectiveness, risks and recommendations. J Dent Hyg. 2013 Feb;87(1):10-8. Epub 2013 Feb 5.

  PMID: 23433693 RESULT

• Caruso AA, Del Prete A, Lazzarino AI. Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic. Med Hypotheses. 2020 Nov;144:109910. doi: 10.1016/j.mehy.2020.109910. Epub 2020 Jun 1.

  PMID: 32505069 RESULT

• Walsh LJ. Safety issues relating to the use of hydrogen peroxide in dentistry. Aust Dent J. 2000 Dec;45(4):257-69; quiz 289. doi: 10.1111/j.1834-7819.2000.tb00261.x.

  PMID: 11225528 RESULT

• Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018 Jun;7(2):249-259. doi: 10.1007/s40121-018-0200-7. Epub 2018 Apr 9.

  PMID: 29633177 RESULT

• Kariwa H, Fujii N, Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents. Dermatology. 2006;212 Suppl 1(Suppl 1):119-23. doi: 10.1159/000089211.

  PMID: 16490989 RESULT

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Water; Povidone-Iodine; Mouthwashes; Hydrogen Peroxide; Cetylpyridinium; hydrated silica gel-based toothpaste; Sodium Hypochlorite

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)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Iodophors; Iodine Compounds; 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; Specialty Uses of Chemicals; Chemical Actions and Uses; Cosmetics; Peroxides; Reactive Oxygen Species; Free Radicals; Pyridinium Compounds; Pyridines; Hypochlorous Acid; Chlorine Compounds; Sodium Compounds

Study Officials

• MANAR M ALZAHRANI, MSD, FRCD(C)

  King Abdulaziz University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Allocated mouth rinses will be concealed in opaque sealed envelopes. Each envelope contains a 15 ml sterile amber test tube filled with the assigned mouth rinse, a 120 ml sterile empty specimen container for expectoration of the mouth rinse, and four identical empty 50 ml sterile test tubes for collecting saliva samples, each labeled with the allocated number and time point (T0, T1, T2, or T3), and a biohazard bag.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 22, 2021
• Study Start: January 3, 2021
• Primary Completion: March 28, 2021
• Study Completion: December 10, 2021
• Last Updated: July 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)