Antiviral Efficacy of Oral Rinses for Inactivation of COVID-19 (MOR2)
Phase: NA
Conditions: COVID-19, Coronavirus Infection, SARS CoV 2 Infection
Sponsor: University of North Carolina, Chapel Hill

 
 
Efficacy of Oral Rinses for Inactivation of COVID-19 (MOR2) 
 
 
 
 
 
 
 
NCT Number 
 
NCT05178173 
Document Date  
03/25/2024 
 
 

 Clinical Intervention Study Protocol 
 
Antiviral Efficacy of Therapeutic Antiseptic Mouth Rinses 
for Inactivation of  
COVID SARS-2 Virus 
A randomized, placebo-controlled, double-masked clinical trial of antiseptic 
mouthwashes in the inactivation of COVID-19 SARS-2 virus in saliva 
 
Study Chairman or Principal Investigator:   
Laura Jacox, DMD, PhD, MS, Assistant Professor of Research and Orthodontics, 
UNC Adams School of Dentistry 
 
Supported by: 
UNC Adams School of Dentistry 
 
Study Intervention Provided by: N/A 
 
 
 
Tool Revision History 
Version Number: 3 
Version Date: March 25, 2024 
 
 
 
 
 

 
TABLE OF CONTENTS 
 
Clinical Intervention Study Protocol Template 
PREFACE 
FULL PROTOCOL TITLE 
Tool Revision History 
TABLE OF CONTENTS 
STUDY TEAM ROSTER 
PARTICIPATING STUDY SITES 
PRÉCIS 
1. STUDY OBJECTIVES 
1.1    Primary Objective 
1.2    Secondary Objectives 
1.3 Tertiary Objectives 
2. BACKGROUND AND RATIONALE 
2.1    Background on Condition, Disease, or Other Primary Study Focus 
2.2    Study Rationale 
3. STUDY DESIGN 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1    Inclusion Criteria 
4.2    Exclusion Criteria 
4.3    Study Enrollment Procedures 
5. STUDY INTERVENTIONS 
5.1    Interventions, Administration, and Duration 
5.2    Handling of Study Interventions 
5.3    Concomitant Interventions 

5.3.1 
Allowed Interventions 
5.3.2 
Required Interventions 
5.3.3 
Prohibited Interventions 
5.4    Adherence Assessment 
6. STUDY PROCEDURES 
6.1    Schedule of Evaluations 
6.2    Description of Evaluations 
6.2.1 
Screening Evaluation 
6.2.2 
Enrollment, Baseline, and/or Randomization 
6.2.3 
Blinding 
6.2.4 
Followup Visits 
6.2.5 
Completion/Final Evaluation 
7. SAFETY ASSESSMENTS 
7.1    Specification of Safety Parameters 
7.2    Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
7.3    Adverse Events and Serious Adverse Events 
7.4    Reporting Procedures 
7.5    Follow-up for Adverse Events 
7.6    Safety Monitoring 
8. INTERVENTION DISCONTINUATION 
9. STATISTICAL CONSIDERATIONS 
9.1    General Design Issues 
9.2    Sample Size and Randomization 
Treatment Assignment Procedures 
9.3    Definition of Populations 
9.4    Outcomes 
9.4.1 
Primary Outcome 
9.4.2 
Secondary Outcomes 
9.4.3 
Tertiary Outcomes 
9.5    Data Analyses 
10. DATA COLLECTION AND QUALITY ASSURANCE 

10.1  Data Collection Forms 
10.2  Data Management 
10.3  Quality Assurance 
10.3.1   
Training 
10.3.2   
Quality Control Committee 
10.3.3   
Metrics 
10.3.4   
Protocol Deviations 
10.3.5   
Monitoring 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY 
11.1  Institutional Review Board (IRB) Review 
11.2  Informed Consent Forms 
11.3  Participant Confidentiality 
11.4  Study Discontinuation 
12. COMMITTEES 
13. PUBLICATION OF RESEARCH FINDINGS 
14. REFERENCES 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
STUDY TEAM ROSTER 
Laura Jacox, Principal Investigator, 2090 First Dental, 385 S. Columbia St., Chapel 
Hill, NC 27599, (847) 702-0988, ljacox@live.unc.edu 
Shannon Wallet, Co-Investigator, 385 S. Columbia St., Chapel Hill, NC 27599, (919) 
537-3359, shannon_wallet@unc.edu 
Ralph Baric, Co-investigator, 3304 Michael Hooker Res Building CB #7435, Chapel 
Hill, NC 27599, (919) 966-3895, rbaric@email.unc.edu 
Natalie Bowman, Co-investigator, CB 7030 Bioinformatics Building, 130 Mason 
Farm Road, Chapel Hill, NC 27514, natalie_bowman@med.unc.edu 
S.T. Phillips, Study Coordinator, GO Health Clinic, 2040 Old Dental, 385 S. 
Columbia St., Chapel Hill, NC 27599, (919) 537-3424, sherrill_phillips@unc.edu 
Clare Bocklage, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 27599, 
(919) 843-2596, eclare@live.unc.edu 
Nare Ghaltakhchyan, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 
27599, 1 (919) 962-2078, nare@live.unc.edu 
Ellie Nanney, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 27599,   
(704) 651-4579, ellien@ad.unc.edu 
Wendy Lamm, Research Assistant, GO Health Clinic, 2040 Old Dental, 385 S. 
Columbia St., Chapel Hill, NC 27599, (919) 537-3418, wendy_lamm@unc.edu 
Payton Mince, Research Assistant, GO Health Clinic, 2040 Old Dental, 385 S. 
Columbia St., Chapel Hill, NC 27599, (919) 537-3418, pmince@ad.unc.edu 
Carol Culver, GO Health Clinic Manager, 2040 Old Dental, 385 S. Columbia St., 
Chapel Hill, NC 27599, (919) 537-3176, carol_culver@unc.edu 
Kevin Moss, Statistician, 385 S. Columbia St., Chapel Hill, NC 27599, (919) 573-
3200, kevin_moss@unc.edu 
Chris Wiesen, PhD. Statistician (survey data), Howard W. Odum Institute for 
Research in Social Science, Davis Library, 208 Raleigh St., Chapel Hill, NC 27514 
USA, 1 (919) 357-3583, chris_wiesen@unc.edu 
 
 
 
 

 
 
PARTICIPATING STUDY SITES 
 
Study Site: UNC Adams School of Dentistry 
 
GO Health Clinic, Old Dental Building #2040 
 
CB# 7450 
 
385 S. Columbia St, Chapel Hill, NC 27599 
 
(919) 537-3424 (P), (919) 843-1798 (F) 
 
Laura Jacox, Principal Investigator, 2090 First Dental, 385 S. Columbia St., Chapel Hill, 
NC 27599, (847) 702-0988, ljacox@live.unc.edu 
Shannon Wallet, Co-Investigator, 385 S. Columbia St., Chapel Hill, NC 27599, (919) 
537-3359, shannon_wallet@unc.edu 
Ralph Baric, Co-investigator, 3304 Michael Hooker Res Building CB #7435, Chapel 
Hill, NC 27599, (919) 966-3895, rbaric@email.unc.edu 
Natalie Bowman, Co-investigator, CB 7030 Bioinformatics Building, 130 Mason Farm 
Road, Chapel Hill, NC 27514, natalie_bowman@med.unc.edu 
S.T. Phillips, Study Coordinator, GO Health Clinic, 2040 Old Dental, 385 S. Columbia 
St., Chapel Hill, NC 27599, (919) 537-3424, sherrill_phillips@unc.edu 
Clare Bocklage, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 27599, (919) 
843-2596, eclare@live.unc.edu 
Nare Ghaltakhchyan, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 27599, 1 
(919) 962-2078, nare@live.unc.edu 
Ellie Nanney, Study Coordinator, 385 S. Columbia St., Chapel Hill, NC 27599, (704) 
651-4579, ellien@ad.unc.edu 
Wendy Lamm, Research Assistant, GO Health Clinic, 2040 Old Dental, 385 S. Columbia 
St., Chapel Hill, NC 27599, (919) 537-3418, wendy_lamm@unc.edu 
Payton Mince, Research Assistant, GO Health Clinic, 2040 Old Dental, 385 S. Columbia 
St., Chapel Hill, NC 27599, (919) 537-3418, pmince@ad.unc.edu 
Carol Culver, GO Health Clinic Manager 2040 Old Dental, 385 S. Columbia St., Chapel 
Hill, NC 27599, (919) 537-3176, carol_culver@unc.edu 
Kevin Moss, Statistician, 385 S. Columbia St., Chapel Hill, NC 27599, (919) 573-3200, 
kevin_moss@unc.edu 

Chris Wiesen, PhD. Statistician (survey data), Howard W. Odum Institute for Research in 
Social Science, Davis Library, 208 Raleigh St., Chapel Hill, NC 27514 USA, 1 (919) 
357-3583, chris_wiesen@unc.edu 
 
 
 
PRÉCIS 
Study Title 
Antiviral Efficacy of Therapeutic Antiseptic Mouth Rinses for Inactivation of COVID 
SARS-2 Virus 
Objectives 
The primary objective is to quantify the impact of antiseptic mouthwashes on salivary 
infectivity in COVID-19+ patients. The secondary objective is to determine patients’ 
acceptance of using antiseptic mouthwashes in healthcare settings. 
Design and Outcomes  
Randomized, double-blind prospective trial to test the efficacy and acceptability of 
two therapeutic, antiseptic mouth rinses to inactivate SARS-CoV-2 virus in saliva of 
COVID-19 positive patients aged 18-65 years old. Both mouth rinses are 
commercially available and will be used according to on-label instructions. Patients 
will be randomized to a mouth rinse 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 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 one, 
75-90 minute visit. 
Interventions and Duration 
Subjects will be asked to rinse with an unlabeled/blinded antiviral mouth rinse for 60 
seconds and provide 5 mL of saliva prior to the rinse and 2 mL of saliva immediately 
post-rinse, 15 minutes post-rinse, 30 minutes post-rinse, 45 minutes post-rinse, and 60 
minutes post-rinse. Subjects will also be asked to complete a short survey about the 
rinsing experience. Subjects will be onsite for a 70-90 minute, single visit 
appointment.  
Sample Size and Population 
We will enroll 84 COVID+ subjects per mouth rinse, with 3 mouth rinses (including a 
water control), requiring us to enroll 252 COVID+ patients. Patients will be 

randomized to their selected mouth rinse assignment. These patients will have already 
had a confirmed COVID+ test within 10 days prior to enrollment. In addition to 
having a COVID+ test, patients will need to be at least 18 years of age and at most 65 
years of age and in good oral health without any known allergies or reactions to the 
ingredients of the mouth rinses. Patients who are pregnant/ nursing/lactating, have a 
cognitive or developmental disability, have an active oral herpes flare up, have any 
oral viral infection and/or flare up, have significant mucosal tears, growths or damage 
to their mouth, have uncontrolled severe periodontal disease with bleeding gums, or 
have xerostomia will be excluded from the study. There is no exclusion criteria based 
on gender or race. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
1. STUDY OBJECTIVES 
1.1   
Primary Objective 
The primary objective of this study is to determine the efficacy of antiseptic 
mouthwashes on reducing SARS-CoV-2 cellular infectivity in COVID+ patient saliva. 
We hypothesize that COVID-19+ patients will have a >95% reduction in SARS-CoV-2 
viral infectivity following a 60 second oral rinse with an antiseptic mouth rinse and 
that this reduction will persist for at least 30 minutes. This primary objective will focus 
on quantifying SARS-CoV-2 viral infectivity and RNA level using an in vitro 
infectivity assay and quantitative real time PCR. This objective provides urgently 
needed data to guide healthcare workers on the proper use of specific commercially 
available mouthwashes capable of reducing SARS-CoV-2 viral infectivity and 
potentially limiting COVID-19+ transmission.  
1.2   
Secondary Objectives 
There is no secondary objective. 
1.3   
Tertiary Objectives 
 
The tertiary objective is to determine the acceptability of using antiseptic mouthwashes 
on reducing SARS-CoV-2 cellular infectivity by patients in various settings including 
healthcare contexts. We hypothesize that patients will welcome the use of commercially 
available antiseptic mouth rinses into clinical practice.  All patients enrolled will be 
surveyed on the taste, appearance, sensation, and acceptability of using the mouth rinse 
in different settings. Understanding acceptability of a mouth rinse protocol is critical to 
implementation and therefore the ability to reduce COVID-19 transmission risk in 
clinical settings. 
 
 
 
 

 
 
 
 
 
2. BACKGROUND AND RATIONALE 
2.1   
Background on Condition, Disease, or Other Primary Study Focus 
The COVID-19 global pandemic, caused by SARS-CoV-2 virus, represents a public 
health emergency with severe societal and economic impacts. Evaluating the potential for 
antiviral mouth rinses to inactivate SARS-CoV2 holds great potential for quelling the 
virus’ spread among healthcare workers, who comprised up to 10% of COVID-19 cases 
early in the pandemic.1,2 Healthcare providers like dentists, who deliver care in and near 
the oropharynx, suffer the highest risk of occupational exposure, if using inadequate 
PPE.3 This is because SARS-CoV-2 is transmitted primarily through aerosol and 
respiratory droplets and salivary glands are a site of early SARS-CoV-2 viral replication 
and transmission.4,5 Dentists work in close proximity to the mouth and nasal passages 
with many procedures producing salivary airborne particles, particularly those involving 
ultrasonic and rotary instruments (hand pieces, “drills”) and 3-way syringes.5–8  High 
rates of SARS-CoV-2 transmission suggest that the minimum infectious dose is low 
compared to other viral diseases, and recent data suggest even one viral particle may be 
sufficient for infection.9 Working in close proximity to the oropharynx and generating 
salivary aerosols increases viral load exposure and therefore the risk of infection among 
dentists, oral surgeons, and other interventional doctors of the face.9 Furthermore, the 
proclivity of aerosols to remain airborne for up to 3 hours puts other patients, providers 
and staff at risk of exposure during aerosol-generating procedures, particularly in open 
bay clinics common to dental schools and large practices.4–6,10 
One promising strategy to reduce clinical spread is use of antiviral mouth rinses to 
inactivate SARS-CoV-2 infectability in saliva. Several commercially available mouth 
rinses have promising in vitro data with SARS-CoV-2 and in vivo data with other 
enveloped viruses, with a proposed mechanism of membrane disruption.3,11 Ethanol 
solutions (21% EtOH) have been shown to reduce SARS-CoV-2 viral infectivity levels in 
vitro, and in patients suffering Herpes Simplex Virus-1 flare-ups, a 30 second oral rinse 
significantly reduced salivary infectivity for over 30 minutes.12 Cetylpyridinium chloride 

(CPC) has promising in vitro data for inactivating SARS-CoV-2 infectivity.13 Minimal in vivo 
clinical data regarding SARS-COV-2 exists to-date for most oral rinses.  
Despite promising in vitro data, there is a dearth of in vivo clinical trials interrogating the 
efficacy of mouth rinses on reducing salivary SARS-CoV-2 viral infectivity. Given the 
rapid transmission and widespread distribution of the COVID-19 pandemic, the 
development of protocols and treatments mitigating transmission represent a major and 
urgent unmet public health need; this study will rigorously address the in vivo utility of 
widely available oral rinses in limiting SARS-CoV-2 viral infectivity and their 
acceptability in the dental healthcare setting. 5–8 Our data from a smaller, prior study 
indicate that rinsing with Ethanol or CPC-containing products reduces salivary viral load 
by qPCR. As a result, we focus this investigation on evaluating the efficacy of an ethanol 
solution and a CPC solution to reduce salivary viral load and infectivity.  
 
1.        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). 
2.        Sorveglianza Integrata COVID-19 in Italia. Instituto Superiore di 
Sanitahttps://portale.fnomceo.it/wp-content/uploads/2020/04/Infografica_9aprile-ITA.pdf 
(2020). 
3.        O’Donnell, V. B. et al.Potential Role of Oral Rinses Targeting the Viral Lipid 
Envelope in SARS-CoV-2 Infection. Function 1, (2020). 
4.        Harrel, S. K. & Molinari, J. Aerosols and splatter in dentistry: A brief review of 
the literature and infection control implications. J. Am. Dent. Assoc.(2004) 
doi:10.14219/jada.archive.2004.0207. 
5.        Izzetti, R., Nisi, M., Gabriele, M. & Graziani, F. COVID-19 Transmission in 
Dental Practice: Brief Review of Preventive Measures in Italy. Journal of Dental 
Research(2020) doi:10.1177/0022034520920580. 
6.        Ather, A., Patel, B. & Ruparel, N. Coronavirus Disease 19 (COVID-19): 
Implications for Clinical Dental Care. J. Endod.(2020). 
7.        Baghizadeh Fini, M. What dentists need to know about COVID-19. Oral 
Oncology(2020) doi:10.1016/j.oraloncology.2020.104741. 
8.        Cleveland, J. L. et al.Transmission of blood-borne pathogens in US dental health 
care settings: 2016 update. J. Am. Dent. Assoc.(2016) doi:10.1016/j.adaj.2016.03.020. 

9.        Pfefferle, S. et al.Low and high infection dose transmission of SARS-CoV-2 in the 
first COVID-19 clusters in Northern Germany. medRxiv(2020) 
doi:10.1101/2020.06.11.20127332. 
10.      Ge, Z. yu, Yang, L. ming, Xia, J. jia, Fu, X. hui & Zhang, Y. zhen. Possible 
aerosol transmission of COVID-19 and special precautions in dentistry. Journal of 
Zhejiang University: Science B(2020) doi:10.1631/jzus.B2010010. 
11.      Carrouel, F. et al.COVID-19: A Recommendation to Examine the Effect of 
Mouthrinses with ß-Cyclodextrin Combined with Citrox in Preventing Infection and 
Progression. J. Clin. Med.(2020) doi:10.3390/jcm9041126. 
12.      Dennison, D. K., Meredith, G. M., Shillitoe, E. J. & Caffesse, R. G. The antiviral 
spectrum of Listerine antiseptic. Oral Surgery, Oral Med. Oral Pathol. Oral 
Radiol.(1995) doi:10.1016/S1079-2104(05)80124-6. 
13.      Statkute, E., Rubina, A., O’Donnell, V., Thomas, D., & Stanton, R. The Virucidal 
Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro. BiorXiv. 
doi.org/10.1101/2020.11.13.381079 
 
2.2   
Study Rationale 
One promising strategy to reduce clinical spread is use of antiviral mouth rinses to 
inactivate SARS-CoV-2 infectability in saliva. Several commercially available mouth 
rinses have promising in vitro data with SARS-CoV-2 and in vivo data with other 
enveloped viruses, with a proposed mechanism of membrane disruption.3,11 Ethanol 
solutions (21% EtOH) have been shown to reduce SARS-CoV-2 viral infectivity levels in 
vitro, and in patients suffering Herpes Simplex Virus-1 flare-ups, a 30 second oral rinse 
significantly reduced salivary infectivity for over 30 minutes.12 Cetylpyridinium chloride has 
promising in vitro data for inactivating SARS-CoV-2 infectivity.13 Minimal in vivo clinical data 
regarding SARS-COV-2 exists to-date for most oral rinses.  
Despite promising in vitro data, there is a dearth of in vivo clinical trials interrogating the 
efficacy of mouth rinses on reducing salivary SARS-CoV-2 viral infectivity. Given the 
rapid transmission and widespread distribution of the COVID-19 pandemic and its new 
variants, the development of protocols and treatments mitigating transmission represent a 
major and urgent unmet public health need; this study will rigorously address the in vivo 
utility of widely available oral rinses in limiting SARS-CoV-2 viral infectivity and their 
acceptability in the dental healthcare setting. 5–8 
Like other enveloped viruses, coronaviruses are surrounded by a lipid bilayer which allows 
for spike glycoproteins required for infection to be inserted.3 The mouth rinses proposed 

in this study have shown success in previous studies in disrupting this lipid envelope in 
other viruses, and there is promise that they will do the same to the SARS-CoV-2 virus. 
Effect size: Based on our similar viral load studies evaluating mouth rinse efficacy against 
SARS-CoV-2 and studies about other enveloped viruses, we used power calculations to 
estimate effect size and determine sample size as a function of length of mouth rinse time 
course. With simultaneous comparisons across time points (T0-T1, T1-T2, T0-T2, T2-T3, 
T0-T3, T1-T3), the sample size n=43 for each mouth rinse can detect the effect size in 
Cohen’s d =0.8 at 30 minutes, which is between medium and large, under 80% power and 
0.016 type-I error rate by Bonferroni correction.12 To account for 14% of patients having 
no virus in their saliva and 10% of patient producing insufficient saliva, we plan to enroll 
55 participants per arm.  
Subjects will be required to rinse their mouths with an unlabeled/blinded mouth rinse for 
60 seconds. Per the instructions on the product label, it is recommended to rinse for 30-60 
seconds. The longer rinse-time was chosen for this study in order to maximize the 
antiviral activity of the proposed mouth rinses. The mouth rinses chosen for this study are 
all commercially available products with known antiviral effects. 
The intervention will be administered orally because an oral mouth rinse will be utilized, 
and the dosage will be 20 mL, dependent on the dosage instructions on the product label. 
The duration of the intervention will be 60 minutes, with collection of pooled saliva 
samples pre-rinse and every 15 minutes (0 min, 15 min, 30 min, 45 min, and 60 min) 
post-rinse. This time period was chosen to be similar to that of a typical dental 
appointment. Multiple saliva samples will be collected to show how long the proposed 
mouth rinses are successful in deactivating the virus. 
Known and potential risks include breach of confidentiality, slight discomfort, and a low 
chance of a previously undiagnosed allergy. To minimize risk of breach of 
confidentiality, all patients will be assigned a unique study ID. There will be no other 
subject identifiers on samples or data. The linkage file that relates patient’s names to 
study ID numbers will be stored on a UNC secure server. All desktop computers and 
servers are kept in locked facilities and in accordance with UNC IT/security safeguards 
and policies.  All providers and study researchers have been trained in and abide by 
HIPAA procedures, and confidential patient information will be stored on secured, 
encrypted UNC servers. Patients will already have been provided with their COVID 
status through their healthcare providers, and this confidential medical information will 
not be released by any study personnel. Some patients may perceive the mouth rinse as 
causing some discomfort if they dislike the flavor or the bubbling sensation. A small 
fraction of patients (rare <1%) may be allergic to the mouth rinse. We will ask detailed 
questions in our screening protocol if patients are allergic to any component of the mouth 
rinses, but if a patient answers no to all screening questions regarding allergy and then 
they are allergic, it may lead to an adverse allergic reaction.  

The following table lists adverse effects associated with each mouth rinse proposed in 
this study: 
 
mouth rinse* 
Adverse effects 
26.9% ethanol 
plus essential 
oils 
● 
If more than used for rinsing (20ml) is accidentally swallowed, get 
medical help or contact a Poison Control Center right away. The exact 
amount used for rinsing (20ml) will be dispensed to study participants, 
such that they cannot swallow more than 20ml, to reduce the risk of 
this adverse event.  
● 
Poison control: (800) 222-1222 
 
0.1% 
Cetylpyridinium 
Chloride 
● 
If more than used for rinsing (20ml) is accidentally swallowed, get 
medical help or contact a Poison Control Center right away. The exact 
amount used for rinsing (20ml) will be dispensed to study participants, 
such that they cannot swallow more than 20ml, to reduce the risk of 
this adverse event.   
● 
Poison control: (800) 222-1222 
 
Sterile water 
No contraindications 
 
*All mouth rinses are commercially available in the USA, routinely used in clinical settings, and 
will be used in an on-label manner. 
 
 
3. STUDY DESIGN 
One of the aims of this placebo-controlled, randomized, double-blinded study is to 
determine the efficacy of antiseptic mouthwashes on reducing SARS-CoV-2 cellular 
infectivity in COVID+ patient saliva (described above).  Asymptomatic and symptomatic 
SARS-CoV-2+ subjects will be enrolled in the study (according to Inclusion and Exclusion 
Criteria - Section A.3). Symptomatic SARS-CoV-2+ subjects will be enrolled within 10 
days of symptom onset and/or within 10 days of initial positive test; asymptomatic SARS-
CoV-2+ subjects will be enrolled within 10 days of initial positive test. Positive test results 
will be accepted if they are provided by a medical professional or official testing site. 
Results can appear either in the UNC electronic medical record or be printed from an 
established testing site such as UNC, a local pharmacy, a medical practice, or an established 
lab. At-home positive test results will be accepted when they are confirmed by study 

personnel with a rapid antigen test at the time of visit. Subjects will be seen and samples 
collected in the isolated Clinical Research Space associated with the GoHealth Clinic 
(Adams School of Dentistry, UNC Chapel Hill, North Carolina, USA).  SARS-CoV-2+ 
subjects will be enrolled within 10 days positive test. Study participants who meet all 
inclusion criteria without any exclusion criteria will be randomized to either an 
experimental or control group using a block randomization tool.  
Participants will be asked to give a baseline salivary sample (5ml over 5 minutes) and then asked 
to rinse with an unlabeled (blinded) antiseptic mouth rinse for 60 seconds according to the table 
below. The rinses and control will be similar in appearance visually, such that a double-blind can 
be maintained. The research assistant (Wendy Lamm) will be the sole unblinded staff member who 
will perform randomization and communicate the subject’s group assignment to blinded study 
staff, in advance of the visit based on the block randomization schedule. The unblinded staff 
member will set-up the rinses for the participants appointment minimizing the possibility of study 
staff being able to identify the blinded rinses. In the instance that Ms. Lamm is unavailable, Ms. 
Payton Mince or Ms. Carol Culver will perform randomization and set-up the rinses. Blind will be 
strictly maintained except in the case of medical emergency requiring reveal of an individual’s 
rinse identity. The product group key will be provided to the analyzing statistician at the conclusion 
of the clinical study. 
mouth rinse* 
Number of participants (sample 
size)  
Group 
26.9% ethanol plus essential oils 
84 
Experimental 
0.1% Cetylpyridinium Chloride 
84 
Experimental 
Sterile water 
84 
Control 
*All mouth rinses are commercially available in the USA, routinely used in clinical settings, and 
will be used in an on-label manner. 
After the participant expectorates the mouth rinse, research staff will collect another 
salivary sample (T0, 2 mL over 5 minutes). During a 10 minute recuperation period, the 
study participants will answer demographics survey questions and questions regarding the 
taste, color, flavor and general acceptability of using the mouth rinse as part of routine 
dental and medical visits as well as in social settings. At 15 minutes post-rinse, the 
participant will be asked to provide an additional saliva sample (2 mL over 5 minutes), 
followed by another 10 minute recuperation period. This sequence will be repeated for at 

the 30, 45 and 60-minute time points post rinse. At 60 minutes, the study participant will 
give their final salivary sample (2 mL over 5 min), and study participation will conclude.   
All salivary samples will be collected on ice in sterile 15 mL conical vials labelled 
“COVID Core” and using pre-printed labels including patient’s random alphanumeric 
study ID. Saliva samples will be cataloged and stored at the UNC Delta COVID 
Translational Initiative (also known as the Covid-19 Core) for future qRT-PCR and viral 
infectivity assays.  Samples will be transported on ice from the collection site to 4403A 
Koury Hall in leak proof biohazard bags. Samples will be processed according to the 
sample processing and outcomes procedure (below).  
Following study participation completion, participants will receive $50 compensation in 
the form of a Visa gift card. 
During the period that the COVID+ study participants are present in the clinic and giving 
saliva samples, we will inquire about their comfort. If participants exhibit signs of distress, 
research study staff will contact emergency medical responders (present in the building) to 
visit the patient and if deemed appropriate, the participants will be escorted to UNC 
hospital (adjacent building). 
This time course analysis design will allow us to determine if any of the antiseptic mouthwashes 
are effective at reducing SARS-CoV-2 in salivary secretions of COVID-19+ study participants as 
well as to determine the therapeutic window if effective. We have designed this study to 
recapitulate a standard oral exam and procedure time (~1 hr in length).  Further, the design will 
allow for a kinetic analysis of viral shedding in salivary secretions and to determine the most 
effective mouth rinse. 
Sample processing and outcomes 
Sample processing: Following collection, saliva samples will be processed according to existing 
BSL2+ SOP protocols (COVID Core, UNC (PI: Wallet and Maile) by pre-authorized personnel. 
Samples will be assessed for 1) molecular presence of SARS-CoV-2, 2) salivary antibody and 
cytokine responses to SARS-CoV-2 and 3) in vitro infectibility. All samples have labels with only 
alphanumeric identifiers thus maintaining the blind and protecting PHI through the entire 
laboratory analysis process. 
1. Molecular analysis: For molecular analysis, samples will be inactivated by adding 2 
mL of extraction buffer to each 500 uL saliva aliquot (4:1 ratio) and mixed by inversion. 
These samples will be further aliquoted at 250uL in 1.5 mL Eppendorf tubes and stored in 
an “Inactivated Samples -80 °C Freezer” until further analysis. 
2. Antibody and cytokine responses: an aliquot of saliva will be inactivated in a 56 °C 
water bath for 30 minutes. 250 uL aliquots will be transferred into 1.5 mL cryovials and 

stored in the “Inactivated Samples -80 °C Freezer” in 4403A Koury Hall until further 
analysis.  
3. In vitro infectivity: Samples will be stored in the “Activated Samples -80 °C Freezer” 
in 4403A Koury Hall until further analysis.  
At analysis, all samples will be serially diluted in sterile PBS (10-10 fold dilutions). Plaque 
assays will be performed using Vero E6 cells at confluency in 96-well cell culture plates. 
Briefly, cell cultures will be washed with sterile PBS and samples containing virus will 
then be plated in duplicate (100 µL per well). Plates will be incubated at 37 °C for 45 
minutes with occasional rocking. Then 2 mL of 0.5% agarose in minimal essential media 
(MEM) containing 2% FBS and antibiotics will be added per well. Plates will be incubated 
at 37 °C for 72 hours, fixed with 10% buffered formalin, followed by the removal of the 
overlay, and then stained with 0.2% crystal violet to visualize plaque forming units (PFU). 
Average PFUs will be evaluated by OD. All assays will be performed in BSL-3 laboratory 
setting. (PMID: 32475066)  
Unprocessed saliva exceeding immediate experimental capacity will be stored in aliquots 
of 250 uL volume in 1.5 mL Eppendorf tubes and stored in “Activated Samples -80C 
Freezer.”  
Survey data: The survey data will be analyzed and used to determine clinical and other 
factors impacting applicability of each of the mouth rinses.  
4. SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1   
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in 
the study: 
● Diagnosed COVID+ status by physician, official testing site, or on-site rapid 
antigen test administered by study personnel at the time of visit. Either became 
symptomatic or initially tested positive in the prior 10 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.  
● 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)  
4.2   
Exclusion Criteria 
Subjects presenting with any of the following will not be included in the study: 
● 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 mouth rinses. (self-reported) 
○ Self-reported allergy to ethanol, essential oils (Eucalyptol, Menthol, 
Methyl salicylate, Thymol), Listerine, Cetylpyridinium Chloride, and 
other components in the mouth rinses. 
○ 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), severe 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 mouth rinse 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 Ethanol rinses 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.  
○ Patient with developmental/cognitive disability that cannot self-consent, 
comprehend and follow the requirements of the study based on research 
site personnel’s assessment.  
○ Patients with sizable mucosal tears, abrasions, growths or burns in the 
mouth  
● The following table lists exclusion criteria specific to each mouth rinse proposed 
in the study: 
mouth rinse* 
Exclusions 
26.9% ethanol plus 
essential oils 
● 
Do not use in children under 12 
0.1% 
Cetylpyridinium 
Chloride 
● 
Do not use in children under 6 
Sterile Water  
 No contraindications 
*All mouth rinses are commercially available in the USA, routinely used in clinical settings, and will be used in an 
on-label manner. 
Summary of Inclusion and Exclusion Criteria for Mouth rinse RCT 
Inclusion Criteria 
Exclusion Criteria 
Individuals (all sex, all gender) at least 18 years of age and at 
most 65 years of age in good oral health and with stable 
physical health, decided at the discretion of the study 
coordinator.  
Known allergies or significant adverse reactions following the 
use of oral hygiene products (toothpastes, mouth rinses), 
commercial cosmetics, iodine, and any ingredient in the mouth 
rinses (list will be provided).  

Diagnosed COVID+ status by physician, official testing site, or 
on-site rapid antigen test administered by study personnel at the 
time of visit. Either became symptomatic or initially tested 
positive in the prior 10 days. 
Established history of severe Xerostomia (drug-induced or 
autoimmune dry mouth), severe periodontal disease with 
actively bleeding gums, significant oral abrasions/ulcers or 
growths, alcohol abuse, and/or recreational drug abuse. 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.  
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. 
Drinking or eating within an hour of the study visit.  
Consuming alcohol within 12 hours of the study visit.  
Rinsing with a commercial mouth rinse within 24 hours of the 
study visit.  
Able to comprehend and follow the requirements of the study 
(including availability on scheduled visit dates) based on 
research site personnel’s assessment.  
Developmental/cognitive disability such that patient cannot 
self-consent, comprehend and follow the requirements of the 
study 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)  
Positive pregnancy test, reported pregnancy or lactation. 
  
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 with 
bleeding gums, or other recent oral viral infection or flare up 
within the past 30 days. 
  
4.3   
Study Enrollment Procedures 
Subjects will be recruited from patients seen in the UNC Respiratory Diagnostic Clinic 
(RDC), UNC testing sites or UNC hospital who have tested positive for COVID+. The subjects 
are being approached by phone or email based off of the UNC RDC/EPIC COVID+ list. 
Subjects will be contacted for recruitment by phone and (if unreachable by phone) by secure 
email by study personnel; patients will have the study rationale and risks explained and will be 
provided time to ask questions and consider participation. If patients are interested in 
participating, a single appointment will be scheduled for them at the Adams School of Dentistry 

Go Health Clinical research core. Consent documentation will be signed in person and in private 
in the Go Health Clinical Research Core.  For hospital in-patients appearing on the EPIC 
COVID+ list, subjects will be approached by a study coordinator in their private hospital room. 
The study's purpose and requirements will be explained and the patient will have the opportunity 
to ask questions and will have time to consider participation. If interested, consent forms will be 
left in the patient’s room for review. Study team members will return later for final consent 
signatures and if consenting, the study visit can occur in their private room. For Spanish 
speaking patients and/or parents, Spanish forms will be provided and communication will occur 
through a Spanish translator. All patients are adults and over normal cognitive capacity, and 
therefore will be able to consent for themselves. A list of COVID+ subjects will be provided by 
the RDC clinic and UNC Epic, available via secure UNC servers and secure UNC email to our 
research team's clinical coordinator, and this list will include names and contact details (PHI). 
This list is updated daily and provided to approved research sites, including ours. 
At the visit, a consented patient will answer screening questions regarding inclusion and 
exclusion criteria. Answers will be entered into the CDART research database managed by 
UNC. Participants lacking a lab or physician confirmed COVID+ test will be administered a 
rapid antigen test by study personnel at the time of their visit to confirm their COVID infection. 
Any participants that produce a negative rapid antigen test (on-site) will be excluded. Prior to 
finalizing these screening questions, women participants of childbearing potential will be asked 
to provide a urine sample in the restroom, to undergo a rapid pregnancy test by study personnel. 
Any pregnant or lactating patients will be excluded.  
Our study statistician, Kevin Moss, will create a block randomization schedule and 
perform these computations. All patients will be consented and then fill out our screening 
questions for inclusion and exclusion to confirm eligibility prior to being assigned to the 
randomization schedule. 
 
5. STUDY INTERVENTIONS 
5.1   
Interventions, Administration, and Duration 
Patients who meet all inclusion criteria without any exclusions will be asked to give a 
baseline salivary sample of 5ml over 5 minutes. The patient will then be asked to rinse 
with an unlabeled/blinded antiseptic mouth rinse for 60 seconds. Once s/he expectorates 
the mouth rinse, a time 0, 2ml salivary sample will be collected over 5 minutes. Then the 
patient will have 10 minutes to recuperate, while answering survey questions about their 
demographics and regarding the taste, color, flavor and acceptability of using the mouth 
rinse as part of routine dental and medical visits. Intra-oral photographs of notable lesions 
may be taken to document oral manifestations of COVID-19. At 15 minutes post-rinse, 
the patient will be asked to provide an additional 2ml saliva samples over 5 minutes, 

followed by another 10 minute break. This sequence repeats for the 30, 45 and 60 minute 
time points. At 60 minutes, the patient will give their last salivary sample, and study 
participation will conclude.  Participants will be provided with a gift card for their 
participation.  
5.2   
Handling of Study Interventions 
Mouth rinses will be acquired from the following sources: 
mouth rinse* 
Source: Online pharmacies and reputable 
marketplaces with over the counter mouth rinses 
26.9% ethanol plus essential oils 
Listerine’s Original Mouth rinse- Amazon or CVS 
online store 
0.1% Cetylpyridinium Chloride 
Crest Pro-Health Mouth rinse- Amazon or CVS 
online store 
Sterile water 
Amazon or CVS online store 
*All mouthrinses are commercially available in the USA, routinely used in clinical settings, and 
will be used in an on-label manner. 
Any adverse events or protocol deviations will be reported to the UNC IRB.  Weekly meetings of 
the internal quality control committee will allow us to closely monitor such events.  
5.3   
Concomitant Interventions 
There are no concomitant interventions other than the mouth rinse and a short survey.  
5.3.1 Allowed Interventions 
There are no additional interventions, other than mouth rinsing with one of the 3 
options previously described. If patients have an allergic reaction, EMS will be 
contacted for management and emergency medical procedures will be followed until 
EMS arrives. If a patient begins experiencing anaphylaxis, we will administer 
epinephrine via an epi-pen, as a rescue medication.  No other rescue medications are 
indicated.  
5.3.2 Required Interventions 
The patient will rinse with a blinded mouth rinse for 60 seconds and then will spit it 
out, followed by donating saliva samples. 
5.3.3 Prohibited Interventions 

Patients who have drank or eaten within an hour of the study visit will be excluded.  
Patients who have consumed alcohol within 12 hours of the study visit.   
Patients who have used a mouth rinse within 24 hours of the study will be excluded. 
Patients who have participated in a study of other oral products (toothpaste, mouth 
rinses) within the prior 30 days will be excluded.  
Patients who are abusers of alcohol or recreational drugs. 
5.4   
Adherence Assessment 
Adherence would be defined as rinsing with the mouth rinse for a full 60 seconds 
before expectorating, and then providing a baseline saliva sample followed by saliva 
samples every 15 minutes four times, until an hour post-rinse (15 min, 30min, 45min, 
60min).    
 
 
6. STUDY PROCEDURES 
6.1   
Schedule of Evaluations 
Assessment 
Phone Screening: (Day-14 to Day -1) 
Final Screening, Baseline, Enrollment, 
Randomization, Intervention: Visit 1 (Day 
0) 
Informed Consent 
Form  
Provided for review 
X  
Demographics 
 
 X 
DXA 
X verbally asked 
X  
Medical History 
 
X  
Current Medications 
 
X 
Rapid Antigen Test- 
COVID+ 
 
X 

Urine Analysis- 
pregnancy 
 
X 
Vital Signs 
 
X 
Inclusion/Exclusion 
Criteria 
X reviewed 
X 
Enrollment/Randomiz
ation 
  
 
X 
Treatment 
Administration Form 
  
X  
Concomitant 
Medications 
 
X 
Adverse Events 
 
X 
6.2   
Description of Evaluations 
Subjects are required to be onsite for a 70-90 minute, single visit appointment. After 
consenting and confirmation of meeting inclusion/exclusion criteria, subjects will be 
asked to rinse with an unlabeled/blinded antiviral mouth rinse for 60 seconds and provide 
5 mL of saliva prior to the rinse and 2 mL of saliva immediately post-rinse, 15 minutes 
post-rinse, 30 minutes post-rinse, 45 minutes post-rinse, and 60 minutes post-rinse. 
Subjects will also be asked questions as part of a short survey about the rinsing 
experience and their willingness to rinse in different situations. 
6.2.1 Screening Evaluation 
Consenting Procedure 
Patients will be contacted first by phone and, if not available, then by email. The consent 
process will be conducted by a study coordinator. The study's purpose and requirements 
will be explained and the patient will have the opportunity to ask questions and will have 
time to consider participation. Interested patients will make an appointment to visit the Go 
Health Clinical Research Unit at Adams School of Dentistry for this study.  Study 
participation includes only one visit. The consent forms will be reviewed and signed by 
interested patients in person in the clinical isolation unit associated with the Go Health 
Clinical Research Unit at Adams School of Dentistry prior to study participation. For 
Spanish speaking patients and/or parents, Spanish forms will be provided and 

communication will occur through a Spanish translator. For hospital in-patients appearing 
on the EPIC COVID+ list, subjects will be approached by a study coordinator in their 
private room. The study's purpose and requirements will be explained and the patient will 
have the opportunity to ask questions and will have time to consider participation. If 
interested, consent forms will be left in the patient’s room for review. Study team members 
will return later for final consent signatures and if consenting, the study visit can occur in 
their hospital room. All patients are adults and have normal cognitive capacity, and 
therefore will be able to consent for themselves. 
Screening 
PreScreening is typically done through a phone call but may be supplemented with email 
correspondence. The screening process is finalized at Visit 1. 
• During the prescreening conversation the patient will answer screening questions 
regarding inclusion and exclusion criteria and will be provided with the informed 
consent to read and review prior to consenting and enrollment process. 
At the visit, participants lacking a lab or physician confirmed COVID+ test will be 
administered a rapid antigen test by study personnel at the time of their visit to confirm 
their COVID infection. Any participants that produce a negative rapid antigen test (on-site) 
will be excluded. Next, women participants of childbearing potential will be asked to 
provide a urine sample in the restroom, to undergo a rapid pregnancy test by study 
personnel. Any pregnant or lactating patients will be excluded. If a participant meets 
enrollment criteria and consents to participate, their answers will be entered into the 
CDART research database managed by UNC. 
 
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
Outpatient subjects will be recruited from patients seen in the UNC Respiratory 
Diagnostic Clinic (RDC), UNC testing sites or UNC hospital who have tested positive for 
COVID-19. Subjects will be contacted for recruitment by phone and (if unreachable by 
phone) by secure email by study personnel; patients will have the study rationale and 
risks explained and will be provided time to ask questions and consider participation. If 
patients are interested in participating, a single appointment will be scheduled for them at 
the Adams School of Dentistry Go Health Clinical research core in the associated clinical 
research isolation area. Consent documentation will be signed in person and in private in 
the Clinical Research Core. A list of COVID+ subjects will be provided by the RDC 
clinic and EPIC, accessible via secure UNC servers or secure UNC email to our research 
team's clinical coordinator, and this list will include names and contact details (PHI). This 
list is updated daily and provided to approved research sites, including ours. 
Baseline Assessments 

Study personnel confirm enrollment qualifying criteria and perform a COVID rapid 
antigen test and pregnancy test on applicable individuals. Otherwise, there are no baseline 
assessments required as this study only requires a 70-90 minute single visit appointment. 
Randomization 
Our statistician will create a block randomization tool which will be provided to the 
unblinded study staff (Wendy Lamm) to perform the randomization. In the instance that 
Ms. Lamm is unavailable, Ms. Payton Mince or Ms. Carol Culver will perform 
randomization and set-up the rinses. The participant’s group assignment will be 
communicated to the blinded clinical staff. All patients will be consented and then 
complete our screening questions for inclusion and exclusion to confirm eligibility prior 
to being assigned to the randomization schedule. 
The researcher in charge of collecting the salivary samples will be blinded to the 
mouthwash solution, as they will be given a pre-aliquoted mouth rinse in an unlabeled 
storage tube to provide to the patient for the rinse.  
6.2.3 Blinding 
At their onsite visit, subjects will be provided with an unlabeled/blinded mouth rinse. The 
researcher in charge of collecting the salivary samples will be blinded to the mouthwash 
solution as well, as they will be given a pre-aliquoted mouth rinse in an unlabeled storage 
syringe to provide to the patient for the rinse. Our statistical consultant, Kevin Moss, will 
set up a randomization schedule that the team will abide by for assignment of enrolled 
subjects.  
6.2.4 Follow-up Visits 
This study requires only one 70-90 minute, single visit appointment. No diagnostic tests 
will be run as part of this clinical trial. All participants will already have known COVID+ 
status. Participants with at-home rapid antigen COVID+ tests will have their COVID 
infection confirmed with a rapid antigen test administered by study personnel at the time 
of visit. Results to the rapid antigen test will be available to participants and study 
personnel 15 minute after being administered. Therefore, no follow-up reporting is 
needed.  
6.2.5 Completion/Final Evaluation 
This study requires only one 70-90 minute, single visit appointment. After consenting and 
randomization, subjects will be asked to rinse with an unlabeled/blinded antiviral mouth 
rinse for 60 seconds and provide 5 mL of saliva prior to the rinse and 2 mL of saliva 
immediately post-rinse, 15 minutes post-rinse, 30 minutes post-rinse, 45 minutes post-

rinse, and 60 minutes post-rinse. Subjects will also be asked to complete a short survey 
about the rinsing experience. 
Subjects may withdraw from the trial at any time at their own request, or they may be 
withdrawn at any time at the discretion of the Investigator or Sponsor for safety, 
behavioral or administrative reasons.  
The Investigator may discontinue a subject if, in the opinion of the Investigator, the 
subject is no longer a suitable candidate for the study. Possible reasons for the 
discontinuation of a subject are including but not limited to: adverse event, protocol 
deviation, missed appointment, subject no longer meets the eligibility criteria. 
Patients may be removed from the study due to an allergic reaction to a mouth rinse or 
due to failure or inability to comply with study procedures.  
If a patient suffers from severe xerostomia/dry mouth, such that s/he cannot produce the 
baseline salivary sample volume or the immediate, 15 minute and 30 minute post-rinse 
saliva volumes, s/he will be removed from the study with a parking voucher, but without 
a gift card and will be replaced. If a patient suffers from dry mouth, such that s/he cannot 
produce salivary sample volumes needed for later time points (45 minutes or 60 minutes 
post-rinse) but s/he produced sufficient baseline, immediate, 15 minute and 30 minute 
post-rinse samples, s/he will still be compensated with a gift card and parking vouchers, 
and will remain in the study. Missing or deficient salivary samples will be noted in 
CDART. Severe xerostomia is an exclusion criteria during screening, yet we anticipate 
that some individuals may not know that they have severe xerostomia until they are 
participating in the study visit and then need to discontinue due to reduced salivary flow, 
as described.   
 
7. SAFETY ASSESSMENTS 
The following table lists possible adverse effects associated with each mouth rinse proposed in 
this study: 
mouth rinse* 
Adverse effects 
26.9% ethanol plus 
essential oils 
● 
If more than used for rinsing (20ml) is accidentally swallowed, get 
medical help or contact a Poison Control Center right away. The 
exact amount used for rinsing (20ml) will be dispensed to study 
participants, such that they cannot swallow more than 20ml, to 
reduce the risk of this adverse event.   
● 
Poison control: (800) 222-1222 
 

0.1% 
Cetylpyridinium 
Chloride 
● 
If more than used for rinsing (20ml) is accidentally swallowed, get 
medical help or contact a Poison Control Center right away. The 
exact amount used for rinsing (20ml) will be dispensed to study 
participants, such that they cannot swallow more than 20ml, to 
reduce the risk of this adverse event.   
● 
Poison control: (800) 222-1222 
 
Sterile Water  
No contraindications 
 
*All mouth rinses are commercially available in the USA, routinely used in clinical settings, and 
will be used in an on-label manner. 
The use of on-label, widely used mouth rinses (like Listerine) and collection of saliva 
carry minimal risk for participants, apart from the very rare, undiagnosed allergy, and 
the unlikely event that the sample is swallowed. If the case of allergy, UNC Hospital 
emergency services will be contacted. In the case of swallowing, a Poison Control 
Center will be contacted.  
7.1   
Specification of Safety Parameters 
Mouth rinse and saliva collection carries low risk and minimal to no safety concerns 
to the participants. Results of analysis from known COVID+ patients will not require 
any medical follow-up or safety concerns. As a result, the investigator will monitor 
subject data, without a safety monitoring board. The investigator and team will meet 
weekly to review safety concerns, unanticipated problems or adverse events.  
7.2   
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
The investigators and study coordinators will meet weekly to review unanticipated 
problems with recruitment or adverse events. There is only one site for this study. The 
use of on-label, widely used mouth rinses (like Listerine) and collection of saliva 
carry minimal risk for participants, apart from the very rare, undiagnosed allergy, 
which would be managed through proper referral to the neighboring UNC hospital. 
7.3   
Adverse Events and Serious Adverse Events 
An adverse event (AE) is generally defined as any unfavorable and unintended 
diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or 
disease which either occurs during the study, having been absent at baseline, or if 
present at baseline, appears to worsen. Adverse events are to be recorded regardless 
of their relationship to the study intervention.  

A serious adverse event (SAE) is generally defined as any untoward medical 
occurrence that results in death, is life threatening, requires inpatient hospitalization 
or prolongation of existing hospitalization, results in persistent or significant 
disability/incapacity, or is a congenital anomaly. 
The use of on-label, widely used mouth rinses (like Listerine) and collection of saliva 
carry minimal risk for participants, apart from the very rare, undiagnosed allergy, or 
the unlikely event that a participant slips or falls during the study, which would be 
managed through proper referral to the neighboring UNC hospital. 
The investigator and team will meet weekly to review safety concerns, unanticipated 
problems or adverse events. All adverse events will be reported to the IRB and the 
committee overseeing the study within 30 days.  
7.4   
Reporting Procedures 
The PI will be responsible to monitor the overall study, including both research data 
and clinical procedures. The PI will be responsible for reporting all adverse events to 
the necessary parties. The investigator and team will meet weekly to review safety 
concerns, unanticipated problems or adverse events. All adverse events will be 
reported to the IRB and the committee overseeing the study within 30 days.  
7.5   
Follow-up for Adverse Events 
In the case of an adverse event, participants will be referred to the neighboring UNC 
hospital. All follow-up visits and procedures regarding adverse events will be handled 
through the UNC Hospital system. A representative from our team will call the 
participant one week after the adverse event occurs to check-in. 
7.6   
Safety Monitoring 
The investigator will monitor subject data, without a safety monitoring board. The 
investigator and team will meet weekly to review safety concerns, unanticipated 
problems or adverse events. 
 
8. INTERVENTION DISCONTINUATION 
Subjects may withdraw from the trial at any time at their own request, or they may be 
withdrawn at any time at the discretion of the Investigator or Sponsor for safety, 
behavioral or administrative reasons.  
The Investigator may discontinue a subject if, in the opinion of the Investigator, the 
subject is no longer a suitable candidate for the study. Possible reasons for the 

discontinuation of a subject are including but not limited to: adverse event, protocol 
deviation, missed appointment, subject no longer meets the eligibility criteria. 
Patients may be removed from the study due to an allergic reaction to a mouth rinse or 
due to failure or inability to comply with study procedures.  
If a patient suffers from xerostomia/dry mouth, such that s/he cannot produce the baseline 
salivary sample volume or the immediate, 15 minute and 30 minute post-rinse saliva 
volumes, s/he will be removed from the study with a parking voucher, but without a gift 
card and will be replaced. If a patient suffers from dry mouth, such that s/he cannot 
produce salivary sample volumes needed for later time points (45 minutes or 60 minutes 
post-rinse) but s/he produced sufficient baseline, immediate, 15 minute and 30 minute 
post-rinse samples, s/he will still be compensated with a gift card and parking vouchers, 
and will remain in the study. Missing or deficient salivary samples will be noted in 
CDART. 
 
 
 
 
 
 
 
 
9. STATISTICAL CONSIDERATIONS  
9.1   
General Design Issues 
A double-blinded, randomized controlled trial was chosen as the study design. It allows us to 
collect human based data on the effects of commercially available mouth rinses on salivary 
infectivity and viral load. A crossover study was not pursued because the repeated use of different 
mouth rinses is likely to confound the results.  A 1-hour time-course was chosen to correspond 
with the average length of most dental procedures. Fifteen minute intervals were chosen to evaluate 
viral kinetics over time, and to see when infectivity rebounds post- mouth rinse.  
Statistical Hypothesis 

The central hypothesis of this study is that a 60 second antiseptic mouth rinse will effectively 
reduce viral infectivity (>50%) of SARS-CoV-2 for a minimum of 30 minutes duration.  
The secondary hypothesis is that a 60 second mouth rinse will be well tolerated in a clinical care 
setting by a majority of patients and providers.  
Sample Size Considerations 
Based on our similar viral load studies evaluating mouth rinse efficacy against SARS-COV-2 and 
other enveloped viruses, we used power calculations to estimate effect size and determine sample 
size as a function of length of mouth rinse time course.12 With simultaneous comparisons, the 
sample size n=43 for each mouth rinse can detect the effect size in Cohen’s d =0.8, which is 
between medium and large, under 80% power and 0.016 type-I error rate by Bonferroni 
correction.12 To account for 14% of patients having no virus in their saliva and 10% of patients 
producing insufficient saliva, we plan to enroll 55 participants per arm. 
Statistical analysis of our deidentified data will be performed by Kevin Moss, the statistician on 
this project.  
Primary Outcomes 
The analyses will compare viral RNA level (qRT-PCR) and viral infectivity levels between mouth 
rinse types and across the time course 
Data generated from the qRT-PCR assays will be presented as mean standard deviation for 
normally distributed data and as median [Interquartile range] for non-normally distributed data. P 
values will be reported as two tailed. Between group comparisons will be performed using a 
Student’s t test or Mann-Whitney U test. Normality will be assessed using the Kolmorgorov-
Smirnov test, and logistic regression will be performed with robust standard errors.  
The viral infectivity analysis will compare infectivity levels between mouth rinse types and across 
the time course for calculation of the reduction factor (RF). The RF will be calculated as the 
difference in the quotient of the infection titre before (‘control titration’) and after the mouth rinse  
(‘remaining virus’). Therefore, the log10 titre and its (double) standard deviation (SD) were 
calculated as well as the variance of the RF. 
Secondary Outcomes 
Survey statistical analysis will be conducted by Odum Institute’s statistical consultant, Chris 
Wiesen, PhD. We will use descriptive statistics, frequency counts and means to evaluate feasibility 
and acceptability of using point-of-care mouth rinses in clinical workflow. 
 
9.2   
Sample Size and Randomization 

Based on similar viral infectivity studies evaluating antiviral mouth rinse efficacy, we were able 
to run power calculations to estimate effect size and determine sample size as a function of 
length of mouth rinse time course. The sample size is justified by a paired t-test on outcomes 
between time points. With simultaneous comparisons, the sample size n=43 for each mouth rinse 
can detect the effect size in Cohen’s d =0.8 at 30 minutes, which is between medium and large, 
under 80% power and 0.016 type-I error rate by Bonferroni correction.12 To account for 14% of 
patients having no virus in their saliva and 10% of patients producing insufficient saliva, we plan 
to enroll 55 participants per arm. 
The statistical consultant on this project will create a block randomization tool for the study staff; 
the unblinded staff member will randomize a participant once enrollment compliance has been 
confirmed and consent has been given. The participant’s group assignment will then be 
communicated to the blinded study staff. IRB approved study personnel will ask participants 
screening questions to confirm eligibility for enrollment. After consent and screening, the 
randomization tool will be used by study staff to assign the subject to a study group.   
The researcher responsible for collecting the salivary samples will be blinded to the mouthwash 
solution, as they will be given a pre-aliquoted mouth rinse in an unlabeled tube to provide to the 
patient for the rinse.  
The PI, Co-I, study coordinators and study personnel who work for GoHealth are authorized to 
break the blinding based on emergency medical necessity such as if a patient suffers an allergic or 
adverse reaction to one of the mouth rinses.  Though highly unlikely as all mouth rinses are sold 
commercially at Walgreens and CVS, adverse or allergic reactions are possible. Using the 
numerical code associated with the participant and mouth rinse syringe, the study personnel 
responding to the emergency can reference the block randomization schedule to determine the 
mouth rinse type, to inform the emergency medical workers, poison control or the emergency room 
what type of mouth rinse product led to the reaction.  
9.3   
Definition of Populations 
Our population includes patients 18-65 years old who have tested positive with 
COVID-19 in the prior 10 days, and/or have symptom development in the prior 10 
days (for symptomatic participants). Inclusion and exclusion criteria (described 
elsewhere) will be met.  We are not treating patients for their COVID-19 infection.  
9.4   
Outcomes 
All oral rinse products are commercially available, low risk products. Therefore, 
adverse outcomes are anticipated to be extremely rare, and will be reviewed weekly 
by the study team/committee.  Any adverse event or deviation will be documented in 
our CDART database system. All significant adverse events (SAEs) will be reported 
appropriately to the IRB. 

 The qRT-PCR and viral infectivity assays for our primary outcome will be 
documented in excel spreadsheets generated by the qRT-PCR and viral infectivity 
assay quantification devices, available weeks to months after sample collection when 
the experiments are conducted. Samples will be run in large batches.  The survey 
results will also yield excel spreadsheets of data, available shortly after data 
collection.  
The outcomes do not include patient treatment response, and therefore the outcomes 
will not be reviewed and adjudicated by an outside committee.  The study personnel 
will constitute their own committee that meets weekly, and they will review and 
evaluate the data once these experiments are conducted. The committee will not be 
masked to the participant’s group assignment; the statistician will conduct analyses 
and then the committee will evaluate the data to reach scientific conclusions on which 
mouth rinse is more effective. 
9.4.1 Primary Outcome  
The primary objective of this study is to determine the efficacy of antiseptic mouthwashes 
on reducing SARS-CoV-2 cellular infectivity in COVID+ patient saliva. We hypothesize 
that COVID-19+ patients will have a >95% reduction in SARS-CoV-2 viral infectivity 
following a 60 second oral rinse with an antiseptic mouth rinse and that this reduction will 
persist for at least 30 minutes. This primary objective will focus on quantifying SARS-
CoV-2 viral infectivity and RNA level using an in vitro infectivity assay and quantitative 
real time PCR. This objective provides urgently needed data to guide healthcare workers 
on the proper use of specific commercially available mouthwashes capable of reducing 
SARS-CoV-2 viral infectivity and potentially limiting COVID-19+ transmission.  
Outcome assessments will be conducted weeks to months after the study visit, when 
qRT-PCR and viral infectivity assays are conducted in the COVID core and the Baric lab.   
9.4.2 Secondary Outcomes  
There is no secondary objective. 
9.4.3 Tertiary Outcomes  
The tertiary objective is to determine the acceptability of using antiseptic mouthwashes on 
reducing SARS-CoV-2 cellular infectivity by patients in settings including healthcare 
contexts. We hypothesize that patients will welcome the use of commercially available 
antiseptic mouth rinses into clinical practice.  All patients will be surveyed on the taste, 
appearance, sensation, and acceptability of using the mouth rinse in healthcare settings. 
Understanding acceptability of a mouth rinse protocol is critical to implementation and 
therefore the ability to reduce COVID-19 transmission risk in clinical settings. 

Survey results will be evaluated using bivariate, descriptive statistics and non-parametric methods 
as appropriate for the question type. Outcome assessments will be conducted weeks to months 
after the study visit, when statistical analyses are conducted. 
9.5   
Data Analyses  All data analyzed will be deidentified.  
qRT-PCR: Data will be presented as mean standard deviation for normally distributed data and as 
median [Interquartile range] for non-normally distributed data. P values will be reported as two 
tailed. Between group comparisons will be performed using a Students t test or Mann-Whitney 
test. Normality will be assessed using the Kolmorgorov-Smirnov test, and logistic regression will 
be performed with robust standard errors. Methods adapted from Bullard et al 2020. 
Viral infectivity: The viral infectivity analysis will compare infectivity levels between mouth rinse 
types and across the time course for calculation of the reduction factor (RF). The RF will be 
calculated as the difference in the quotient of the infection titre before (‘control titration’) and after 
the mouth rinse  (‘remaining virus’). Therefore, the log10 titre and its (double) standard deviation 
(SD) were calculated as well as the variance of the RF. 
Survey results will be evaluated using bivariate, descriptive statistics and non-parametric methods 
as appropriate for the question type.  
Power Calculation: Based on our similar viral load studies evaluating mouth rinse efficacy against 
SARS-COV-2 and other enveloped viruses, we used power calculations to estimate effect size and 
determine sample size as a function of length of mouth rinse time course.12 The sample size is 
justified by a paired t-test on outcomes between time points. With simultaneous comparisons, the 
sample size n=43 for each mouth rinse can detect the effect size in Cohen’s d =0.8, which is 
between medium and large, under 80% power and 0.016 type-I error rate by Bonferroni 
correction.12 To account for 14% of patients having no virus in their saliva, we plan to enroll 55 
participants per arm. Analyses will compare viral RNA level (qRT-PCR) and viral infectivity 
levels between mouth rinse types and across the time course. ANCOVA models will be utilized to 
look at changes in viral load and infectivity logarithmically before and after treatment.  
 
 
 
 
 
 

10. DATA COLLECTION AND QUALITY ASSURANCE  
10.1 
Data Collection Forms 
Consented patients' data (including screening questions, demographics, and the survey on 
mouth rinse acceptability) will be collected using the CDART dental toolkit program, 
which stores data on a secure UNC maintained server and meets federal guidelines for 
clinical study data acquisition. The CDART electronic forms and database will serve as 
our CRFs and source data. IRB approved study personnel will ask participants the 
questions and will enter responses into this encrypted, password protected database. Data 
will be collected in this program using participant's study ID and no other personal health 
identifiers (PHI). A separate linkage file for participants ID and name will be set-up and 
maintained by the study coordinators and will be securely stored on UNC servers. This 
linkage file will be kept confidential. and not shared with anyone outside of the study 
coordinators. Clinical data will only be transmitted among the research team using the 
school of dentistry secure research servers. Demographic data will be transmitted among 
the research team through access to the secure CDART research database system, stored 
on secure UNC servers, which study personnel will access only through encrypted 
computers via secure user accounts. 
 
10.2 
Data Management 
An Excel key will be created by the study coordinators with study ID (random 
alphanumeric code) to identify patients, saved in a secure folder on a UNC SOD server. 
This linkage file will be stored separately from data and destroyed at the close of the 
study and will never be shared beyond the study coordinators.    
All data collected from participants and results from sample analysis will be coded with 
unique numerical identifiers and stored in the UNC CDART clinical research database 
and on a secure UNC-CH server. Only trained, IRB-approved study personnel will enter 
and access data in the secure CDART research database. 
Consented patients' data (including screening questions, demographics, and the survey on 
mouth rinse acceptability) will be collected using the CDART dental toolkit program, 
which stores data on a secure UNC maintained server and meets federal guidelines for 
clinical study data acquisition. Only HIPAA and human subjects trained, IRB-approved 
study personnel will collect, enter and manage patient data; study coordinators will serve 
in this capacity.  
Data will be collected in the CDART research database using participant's study ID and 
no other PHI identifiers, on approved, carefully designed digital forms within CDART. 
CDART forms will include questions with drop downs, radio button multiple choice and 
text field entry, depending on the question type. There will be separate digital forms for 
inclusion/exclusion screening questions (before sample collection begins), demographic 

questions, and questions regarding mouth rinse experience (taste, color, sensation)  and 
willingness to use a mouth rinse in various settings (e.g. dentist or doctor appointments). 
A separate linkage file, securely stored on UNC servers, will be utilized to associate the 
random alphanumeric study ID with patient identifier, so samples and CDART data will 
not be associated with patient identifiers.  
Data will only be transmitted among the research team using the SOD secure research 
server. Demographic data will be transmitted among the research team through access to 
the secure CDART research database system, stored on secure UNC servers, which study 
personnel will access only through encrypted computers via secure user account. 
Linkage files containing identifiers will be deleted and permanently removed from all 
servers and study computers at the conclusion of the study with acceptance of associated 
manuscripts. Saliva specimens will be labeled with a study ID (random alphanumeric 
code) that is not identifiable without the linkage file, and therefore will not be identifiable 
after linkage file destruction.  
The quality control committee (described below) will be in charge of monitoring these 
forms and the CDART database.  
 
10.3 Quality Assurance 
 
The Clinical Quality Management Plan (CQMP) establishes the quality 
management guidelines this study, also referred to as MOR2. The purpose of the CQMP 
is to identify and document the ongoing processes and activities that will be used to 
monitor and facilitate quality protocol execution following study initiation. Quality 
measures related to study development and start-up are not included in this plan. An 
individual who has no other role on the study team will be responsible for execution of 
this plan. 
 
QM Activity Schedule and Tools 
Quality Management (QM) activities will be conducted for each enrolled study subject. 
Additional QM activities and reviews will be conducted on an as-needed basis in 
response to staff or process changes.    
The site Quality Assurance Coordinator (QAC) will use the Quality Management Subject 
Data Review Tool to review completion and accuracy of the source documents, eCRFs 
and Delegation of Responsibility (DOR).   
The following outlines the QM process: 
• The QAC will maintain the CQMP and QM tools/logs in electronic folder. 
• The QAC will review 100% of the executed consents using the QM Subject Data Review 
Tool. The QAC will verify form completion and accuracy and verify that the most 
current IRB-approved study consent documents are being used. 
• The QAC will review 100% of CDART eCRF data. This includes all eCRF records 
containing CRF and/or source documentation. The QAC will verify completion of study 
data entry, subject dispositions and if any unanticipated problems, adverse events, 

promptly reportable events and/or protocol deviation have been documented and reported 
to local IRB as required by the UNC Office of Research Ethics.     
• The QAC will review completion of the Delegation of Responsibilities (DOR) prior to 
study start and upon new study personnel. 
• At an interval of 10 enrolled subjects, the QAC will randomly select one subject and 
review all source documentation and any other corroboration documentation for eCRF 
data entry, all eCRF’s and pregnancy log (if applicable). 
• This CQMP will be a living document and will be reviewed for applicability and 
accuracy and updated as necessary by the QAC. Upon each review, the QAC will provide 
the study team feedback and report items covered by the review, identification of 
problem areas and trends, suggest corrective action plan(s) (if applicable), and if/when 
there is a need for revision to CQMP. Additional QM needs identified will be 
communicated to the study team where needed and revisions made upon request of the 
Investigator.  
 
10.3.1  Training 
All study personnel have been trained in health privacy (HIPAA) and human subjects 
research through the CITI program and are certified to work with patient data on clinical 
trials. Study coordinators and healthcare providers are trained in and approved for the use 
of the CDART electronic research database and EPIC medical record system. Technical 
research personnel performing viral PCR and infectivity assays are approved to operate in 
their BL3 laboratory facilities and have specialized, lab-based training in these molecular 
techniques. They have also undergone training in the use of universal precautions and 
management of human biological samples along with bloodborne pathogen training. 
Finally, the GoHealth Clinical Research core has highly experienced research 
coordinators who will monitor all study staff to ensure protocol compliance and quality 
assurance.    
10.3.2  Quality Control Committee 
Findings of the site Quality Assurance Coordinator (QAC) will be presented to the 
investigators and study coordinators (as appropriate for the findings) at selected weekly 
meetings for discussions and remediation actions as appropriate.  There is only one site 
for this study. The use of on-label, widely used mouth rinses (like Listerine) and 
collection of saliva carry minimal risk for participants, apart from the very rare, 
undiagnosed allergy, which would be managed through proper referral to the neighboring 
UNC hospital. Therefore, there is no study quality control committee.  
10.3.3  Metrics 
Every salivary sample will be collected in a conical tube with millimeter markings to 
monitor salivary volume. If insufficient saliva is collected, the study personnel collecting 

the samples from participants will note insufficient volume in the CDART database for 
each applicable time point and will indicate in CDART if the subject must be withdrawn 
and replaced. If a patient is unable to generate sufficient saliva for the 0 min, 15 minutes 
or 30 minutes post-rinse time points, the subject will be removed from the study and this 
will be noted in CDART along with their insufficient samples. If a subject is unable to 
generate sufficient saliva for time points 45 or 60 minutes post-rinse, the patient will 
remain in the study but their insufficient samples will be noted in CDART.   
For RT-PCR and viral infectivity assays, all salivary samples will be run in triplicate with 
standard experimental controls (negative and positive) and protocol quality checks 
performed by research technical personnel in the COVID core, Baric, Webster and Wallet 
laboratories.  
10.3.4  Protocol Deviations 
Protocol deviations will be recorded within the source documentation for each participant 
within the CDART study database by study personnel during the study visits.  The 
investigators and study coordinators will meet weekly to review unanticipated problems, 
adverse events and protocol deviations recorded in the CDART study database. All such 
events will be appropriately reported to the IRB board of UNC.  
10.3.5  Monitoring 
Findings of the site Quality Assurance Coordinator (QAC) will be presented to the 
investigators and study coordinators (as appropriate for the findings) at selected weekly 
meetings for discussions and remediation actions as appropriate.  The QAC and the lead 
study coordinator will make recommendations to the PI if needed outside of the regularly 
weekly study team meetings. 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY 
11.1 
Institutional Review Board (IRB) Review 
This protocol and the informed consent document and any subsequent modifications 
will be reviewed and approved by the IRB or ethics committee responsible for 
oversight of the study. Consent forms are separate from this protocol document and 
were submitted as part of the IRB application. 
11.2 
Informed Consent Forms 
Patients who have tested positive for COVID-19 in the UNC Respiratory Diagnostic 
Clinic (RDC), UNC testing sites or UNC hospital will be contacted to participate in this 
study by research personnel. Patients will be contacted first by phone and, if not 
available, then by email. The study's purpose and requirements will be explained and the 

patient will have the opportunity to ask questions and will have time to consider 
participation. Interested patients will make an appointment to visit the clinical isolation 
area associated with the Go Health Clinical Research Unit at Adams School of Dentistry 
for this study.  Study participation includes only one visit. The consent forms will be 
reviewed and signed by interested patients in person in the isolation area adjacent to the 
Go Health Clinical Research Unit at Adams School of Dentistry.  
For hospital in-patients appearing on the EPIC COVID+ list, subjects will be approached 
by a study coordinator in their private room. The study's purpose and requirements will 
be explained and the patient will have the opportunity to ask questions and will have time 
to consider participation. If interested, consent forms will be left in the patient’s room for 
review. Study team members will return later for final consent signatures and if 
consenting, the study visit can occur in the patient’s room. 
A signed consent form will be obtained from each participant. For participants who 
cannot consent for themselves, such as those with a legal guardian (e.g., person with 
power of attorney), this individual must sign the consent form, though minors and 
patients who are intellectually delayed and unable to consent for themselves will be 
excluded. The consent form will describe the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation. A copy will be offered to each 
participant or legal guardian and this fact will be documented in the participant’s record. 
For Spanish speaking patients and/or parents, Spanish forms will be provided and 
communication will occur through a Spanish translator. All patients are adults and over 
normal cognitive capacity, and therefore will be able to consent for themselves. 
At the visit, a consented patient will answer screening questions regarding inclusion and 
exclusion criteria. Answers will be entered into the CDART research database managed 
by UNC. Prior to finalizing these screening questions, women participants of 
childbearing potential will be asked to provide a urine sample in the restroom, to undergo 
a rapid pregnancy test by  study  personnel. Any pregnant or lactating patients will be 
excluded.  
Our study statistician will create a block randomization tool and the unblinded staff 
member will randomize participants. All patients will be consented and then answer our 
screening questions for inclusion and exclusion to confirm eligibility prior to being 
assigned to the randomization schedule. 
11.3 
Participant Confidentiality 
An Excel Linkage File key will be created with study ID (random alphanumeric 
code) to identify patients, saved in a secure folder in a UNC School of Dentistry 
(SOD) server, by the unblinded staff member. This linkage file will be stored 
separately from data and destroyed at the close of the study.. All data collected from 
participants and results from sample analysis will be coded with unique numerical 

identifiers and stored in the UNC CDART clinical research database and on a secure 
UNC-CH server. Data will only be transmitted among the research team using the 
SOD secure research server. Demographic data will be transmitted among the 
research team through access to the secure CDART research database system, stored 
on secure UNC servers, which study personnel will access only through encrypted 
computers via secure user account. All research personnel will be trained in 
maintaining patient confidentiality and HIPAA. 
Any data, specimens, forms, reports, and other records that leave the site will be 
identified only by a participant identification number (Participant ID, PID) to 
maintain confidentiality. We do not anticipate any data, specimens, forms reports and 
other records leaving the site as sample storage and analysis will occur on site. All 
paper records will be kept in a locked file cabinet, and all digital records will be 
stored in the encrypted, secure, password protected CDART research database. All 
computer entry and networking programs will be done using PIDs only. Information 
will not be released without written permission of the participant, except as necessary 
for monitoring by IRB, the FDA, the NCCIH, and the OHRP. 
There is little to no potential for deductive disclosures from the survey portion of 
this study. Patients will be asked about the experience rinsing with a commercially 
available mouth rinse (such as Listerine).  They will asked to rate the taste, 
appearance/color, sensation, and their willingness to use the mouth rinse in the future. 
General demographics will be asked such as gender, race, ethnicity and age bracket. 
Their identity cannot be deduced from this information.  
11.4 
Study Discontinuation 
The study may be discontinued at any time by the IRB, the NCCIH, the OHRP, the FDA, 
or other government agencies as part of their duties to ensure that research participants 
are protected. 
12. COMMITTEES 
The IRB committee will review and approve all study documents, and adverse events and 
protocol deviations will be reported to them for review as well.  
13. PUBLICATION OF RESEARCH FINDINGS 
Any presentation, abstract or manuscript will be made available for review and approval 
by the sponsor and all authors prior to submission.  
14. REFERENCES 

1.        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). 
2.        Sorveglianza Integrata COVID-19 in Italia. Instituto Superiore di 
Sanitahttps://portale.fnomceo.it/wp-content/uploads/2020/04/Infografica_9aprile-ITA.pdf 
(2020). 
3.        O’Donnell, V. B. et al.Potential Role of Oral Rinses Targeting the Viral Lipid 
Envelope in SARS-CoV-2 Infection. Function 1, (2020). 
4.        Harrel, S. K. & Molinari, J. Aerosols and splatter in dentistry: A brief review of 
the literature and infection control implications. J. Am. Dent. Assoc.(2004) 
doi:10.14219/jada.archive.2004.0207. 
5.        Izzetti, R., Nisi, M., Gabriele, M. & Graziani, F. COVID-19 Transmission in 
Dental Practice: Brief Review of Preventive Measures in Italy. Journal of Dental 
Research(2020) doi:10.1177/0022034520920580. 
6.        Ather, A., Patel, B. & Ruparel, N. Coronavirus Disease 19 (COVID-19): 
Implications for Clinical Dental Care. J. Endod.(2020). 
7.        Baghizadeh Fini, M. What dentists need to know about COVID-19. Oral 
Oncology(2020) doi:10.1016/j.oraloncology.2020.104741. 
8.        Cleveland, J. L. et al.Transmission of blood-borne pathogens in US dental health 
care settings: 2016 update. J. Am. Dent. Assoc.(2016) doi:10.1016/j.adaj.2016.03.020. 
9.        Pfefferle, S. et al.Low and high infection dose transmission of SARS-CoV-2 in the 
first COVID-19 clusters in Northern Germany. medRxiv(2020) 
doi:10.1101/2020.06.11.20127332. 
10.      Ge, Z. yu, Yang, L. ming, Xia, J. jia, Fu, X. hui & Zhang, Y. zhen. Possible 
aerosol transmission of COVID-19 and special precautions in dentistry. Journal of 
Zhejiang University: Science B(2020) doi:10.1631/jzus.B2010010. 
11.      Carrouel, F. et al.COVID-19: A Recommendation to Examine the Effect of 
Mouthrinses with ß-Cyclodextrin Combined with Citrox in Preventing Infection and 
Progression. J. Clin. Med.(2020) doi:10.3390/jcm9041126. 
12.      Dennison, D. K., Meredith, G. M., Shillitoe, E. J. & Caffesse, R. G. The antiviral 
spectrum of Listerine antiseptic. Oral Surgery, Oral Med. Oral Pathol. Oral 
Radiol.(1995) doi:10.1016/S1079-2104(05)80124-6. 

13.      Statkute, E., Rubina, A., O’Donnell, V., Thomas, D., & Stanton, R. The Virucidal 
Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro. BiorXiv. 
doi.org/10.1101/2020.11.13.381079 
 
15. SUPPLEMENTS/APPENDICES 
No supplements or appendices.  All forms are submitted as part of the IRB application.