Clinical trial NCT04364802
Conditions: COVID-19 SARS-CoV 2
Keywords: COVID-19 SARS-CoV 2 Health Care Workers COVID-19 Prophylaxis
Sponsor: Nikita Gupta
Start date: 2020-04-29; Completion date: 2022-01-28
Enrollment: 98 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Povidone-iodine (PVP-I) is a broad-spectrum antiseptic with activity against bacteria, fungi, and viruses. It has been previously used in both intranasal preparations against Methicillin Resistant Staphylococcus Aureus (MRSA) as well as oral preparations in in-vitro studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), influenza H1N1, and rotavirus with good efficacy. This study will evaluate the efficacy of PVP-I as prophylaxis in Coronavirus Disease 2019 (COVID19)-negative front-line health care workers, hospital patients, and community members.

Detailed description:
The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), has been implicated in over 12 million cases and counting in the United States alone and has killed at least 1300 health care workers and \>250,000 citizens. This, added to the national shortage of personal protective equipment (PPE) and the need to reuse PPE, lends to the significantly increased risk to healthcare providers. At the beginning of this trial, there were only 360,000 cases.

The highest concentration of viral particles resides within the nasopharynx. The virus is thought to spread via respiratory droplets with the potential for transmission via inhalation of droplets, contact to the nose and mouth with infected materials, and airborne transmission. Given that frontline workers are involved in high-risk procedures including intubation, bronchoscopy, proning patients (which can lead to droplet production) and in some cases are reusing PPE, finding ways to reduce viral load or viral exposure are paramount.

Povidone-iodine (PVP-I) is a broad-spectrum antiseptic with activity against bacteria, fungi, and viruses. It has been previously used in both intranasal preparations against MRSA as well as oral preparations in in-vitro studies of SARS-CoV-2, MERS-CoV, H1N1, and rotavirus with good efficacy.

Due to the known breadth of its antiviral activity and similarities in molecular structure, it can be extrapolated that PVP-I should have robust activity against SARS-CoV-2. Eggers et al found that at a concentration of 1% there was a reduction of viral activity of 99.99% in in-vitro assays. At 2 minutes, a concentration of 0.23% was enough to reduce viral loads appreciably. New data has demonstrated efficacy in-vitro of PVP-I against SARS-CoV-2 at low concentrations.

PVP-I is widely used as an antiseptic and is well-tolerated and has been shown to have little to no effect on mucociliary clearance, olfaction, or thyroid function if iodine holidays are taken, although care must be utilized in monitoring.

In this study, front line healthcare workers will be asked to complete a pre-participation survey and screened for COVID positivity. They will then be given premade PVP-I gargles and nasal sprays, as well as a calendar card to mark compliance. PVP-I nasal spray and gargle (10% diluted 1:30) will be used prior to the start of a shift, during "lunch break", and at the end of shift. First, the nasal spray will be sprayed in the nose (2 sprays each naris). For adequate coverage, the participant should be able to taste the iodine or see it in the back of the throat. This should be left in place for 30 seconds. Then, the participant will gargle the solution for 30 seconds and not have anything to eat or drink by mouth for 30 minutes. Treatment will continue for 3 weeks, or until the healthcare worker presents with COVID symptoms. Participants will then be tested for COVID positivity and asked to fill out a second questionnaire assessing study tolerability. At completion of the study, they will be asked to turn in their calendar card to assess how many applications they were able to complete.

Given the high rate of asymptomatic carriers, a second arm will also be planned for patients who have a 7+ day hospitalization or who are set to undergo a significant surgical procedure. These patients will be offered participation in the study as well and will be given the same questionnaire and undergo preoperative testing if they consent. For patients in the study group, PVIP gargle and nasal sprays will be applied preoperatively or shortly after admission and enrollment in the study for the non-operative group. The patients will then be retested in 2 weeks or as directed by the presentation of symptoms concerning for infection with SARS-CoV-2.

Community spread has been found to be the most likely implicated in infection and thus the trial is now being expanded to include community members. Thus, a THIRD arm has now been added to include community members. Prescreening questionnaires will be given. As long as the participant has had no prior history of a positive COVID-19 test, they will be considered eligible for participation. After a screening consultation, they will undergo a COVID-19 test (should be completed within 72 hours of screening). If negative, they will be eligible. Participants who are pregnant, breastfeeding, have thyroid disease or cancer, or who have an allergy to iodine/shellfish/or contrast dye can still participate but will automatically be on the control arm. Participants may opt to be on either the PVP-I arm or the control arm. They will be asked to fill out a daily questionnaire regarding their exposures and whether they were wearing a mask or if other people were wearing a mask at that time.

Arms: arm 1: Front-line healthcare workers (FLCHW) who are negative for COVID will receive standard PPE and a pre- and post-study test for COVID-19. arm 2: Front-line healthcare workers (FLCHW) who are negative for COVID-19 will receive standard PPE and a pre- and post-study test for COVID-19. Additionally, they will receive PVP-I spray and gargle. arm 3: Inpatients who have a 7+ day hospitalization or who are set to undergo a significant surgical procedure will receive standard care and a pre- and post-study COVID-19 test. arm 4: Inpatients who have a 7+ day hospitalization or who are set to undergo a significant surgical procedure will receive standard care and a pre- and post-study COVID-19 test. Additionally, they will receive PVP-I gargle and nasal sprays that will be applied shortly after admission or perioperatively. arm 5: Community participants who are negative for COVID-19 will receive a pre- and post-study COVID-19 test. arm 6: Community participants who are negative for COVID-19 will receive a pre- and post-study COVID-19 test. Additionally, they will receive PVP-I gargle and nasal sprays.
Interventions: intervention 1: Povidone-Iodine Nasal Spray and Gargle intervention 2: Povidone-Iodine Nasal Spray and Gargle intervention 3: Povidone-Iodine Nasal Spray and Gargle
Intervention descriptions: intervention 1: Healthcare workers will receive standard PPE and a pre- and post-study nasal swab COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle (10% diluted 1:30) to use at the beginning of their shift, in the middle, and at the end of their shift. intervention 2: Patients will receive standard of care treatment and a pre- and post-study nasal spray COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle shortly after admission or preoperatively. intervention 3: Community members will receive a pre- and post-study nasal swab COVID19 test. Additionally, they will receive povidone-iodine nasal spray and gargle (10% diluted 1:30) to use at home.

Protocol documents:
Prot_ICF_001.pdf: 
Document Coversheet 
 
Study Title: COVID-19: Povidone-Iodine Intranasal Prophylaxis in Front-line Healthcare 
Personnel and Inpatients (PIIPPI) 
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
4/12/22 
NCT Number: 
NCT04364802 
IRB Number 
58748 
Coversheet created: 
8/18/22 
 
 


Consent to Participate in a Research Study 
KEY INFORMATION FOR POVIDONE-IODINE INTRANASAL AND OROPHARYNGEAL GARGLE 
FOR PROPHYLAXIS IN FRONT-LINE PHYSICIANS/HEALTHCARE WORKERS AND INPATIENTS 
TO PREVENT THE SPREAD OF SARS-COV-2 (COVID19) 
We are asking you to choose whether or not to volunteer for a research study about using a nasal spray and 
gargle containing an iodine containing solution while working in the hospital. We are asking you because of the 
high potential for catching COVID19 while in the hospital. This page is to give you key information to help you 
decide whether to participate. We have included detailed information after this page. Ask the research team 
questions. If you have questions later, the contact information for the research investigator in charge of the 
study is below. 
WHAT IS THE STUDY ABOUT AND HOW LONG WILL IT LAST? 
The purpose of this research is to gather information on the safety and effectiveness of povidone-iodine (PVI) 
nasal sprays and gargle to reduce the risk of contracting and spreading COVID19. Your participation in this 
research will last 3 weeks. This preparation is approved by the Food and Drug Administration (FDA) but not 
for this usage. There will be a treatment group that will use PVI and a control group that will provide care as 
usual without using the preparation if they have a contraindication to doing so or would like to opt out but still 
participate.  You will be contacted up to 6 months afterward to assess any further thoughts and experiences.
WHAT ARE KEY REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY? 
Subjects have a theoretical benefit of a reduced risk of contracting and spreading COVID19. It is hypothesized 
that PVI may inhibit viral attachment to cellular receptors and inhibit viral release and spread from infected cells. 
For a complete description of benefits, refer to the Detailed Consent. 
WHAT ARE KEY REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS STUDY? 
You might not want to participate in this trial because it involves having to use a spray in your nose and 
having to gargle three times a day. Iodine can sometimes cause nasal irritation. For a complete description of 
risks, refer to the Detailed Consent and/or Appendix. An alternative to using this spray is using nothing and 
continuing to exercise good hygiene practices. 
DO YOU HAVE TO TAKE PART IN THE STUDY? 
If you decide to take part in the study, it should be because you really want to volunteer. You will not lose any 
services, benefits or rights you would normally have if you choose not to volunteer. 
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS? 
If you have questions, suggestions, or concerns regarding this study or you want to withdraw from the study 
contact Alexandra E. Kejner, MD FACS or Zachary Porterfield MD PhD of the University of Kentucky, 
Department of Otolaryngology at 859-257-5097 or by email at Alexandra.kejner@uky.edu or 
zach.porterfield@uky.edu. 
If you have any concerns or questions about your rights as a volunteer in this research, contact staff in the 
University of Kentucky (UK) Office of Research Integrity (ORI) between the business hours of 8am and 5pm 
EST, Monday-Friday at 859-257-9428 or toll free at 1-866-400-9428. 
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DETAILED CONSENT: 
ARE THERE REASONS WHY YOU WOULD NOT QUALIFY FOR THIS STUDY? 
If you are pregnant, breast-feeding, have thyroid cancer or take thyroid medications, you will not be eligible to use 
the nasal and gargle preparations but will still be eligible to participate in the COVID19 testing and questionnaires 
as what is called the “control group”. 
WHERE WILL THE STUDY TAKE PLACE AND WHAT IS THE TOTAL AMOUNT OF TIME INVOLVED? 
The research procedures will be conducted at the University of Kentucky Chandler Hospital. You will meet with 
the research staff to obtain the initial COVID 19 test and to receive materials and instructions. At the end of the 
study (3 weeks), you will return to meet with the research staff for a follow up COVID 19 test. If you develop 
symptoms at any time during the study period prior to the end of 3 weeks, you should receive a COVID 19 test 
as is standard of care and please report the results to us. A positive test ends your involvement in the study.  
WHAT WILL YOU BE ASKED TO DO? 
You will first be asked to complete a pre-screening questionnaire. Then, if you have never had a positive 
COVID19 test, you will undergo a COVID19 test. You will be given the results of your COVID test as soon as they 
are available. You will then be given the nasal spray and gargle preparation 
You will be asked to do the nasal spray and gargle 3 times a day, for up to 7 days on, with 3 day breaks, 
depending on your work schedule, for a total of 3 weeks. 
IF during the trial, you begin to develop symptoms, you will be tested for COVID19. If during the study period you 
do NOT develop symptoms, you will be re-tested at the end of 3 weeks from beginning use. 
For participants who are not able to use the iodine nasal sprays or gargle, use standard hand hygiene. If you 
begin to develop symptoms, your COVID19 test will be repeated. If during the study period you do NOT develop 
symptoms, you will be re-tested at the end of 3 weeks. 
You will be contacted up to 6 months following your participation to assess your thoughts and experience on trial 
as well as if you ever contracted COVID following participation and if you were vaccinated or not.  This 
information will only be linked to your unique name and will not be shared.
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
Potential risks include foul taste from the PVI, discoloration of the throat and nose. There is a minuscule risk of 
thyroid dysfunction if excess amount of iodine is taken. There is a potential that you could still catch COVID19 
while taking this preparation. There is a chance that you may get nasal irritation and dryness and even a small 
nosebleed while using the nasal spray. 
There is always a chance that any medical treatment can harm you. The research treatments/procedures in this 
study are no different. In addition to risks described in this consent, you may experience a previously unknown 
risk or side effect. 
WILL YOU BENEFIT FROM TAKING PART IN THIS STUDY? 
We do not know if you will get any benefit from taking part in this study. However, there is a possibility that use of 
the nasal spray and irrigation may prevent you from contracting the coronavirus that causes COVID19 while you 
are caring for patients. If you take part in this study, information learned may help others with your condition. 
IF YOU DON’T WANT TO TAKE PART IN THE STUDY, ARE THERE OTHER CHOICES? 
If you do not want to be in the study, there are no other choices except not to take part in the study. 
WHAT WILL IT COST YOU TO PARTICIPATE? 
You and/or your insurance company, Medicare, or Medicaid will be responsible for the costs of all care and 
treatment that you would normally receive for any conditions you may have. These are costs that are considered 
medically necessary and will be part of the care you receive even if you do not take part in this study. 
The University of Kentucky may not be allowed to bill your insurance company, Medicare, or Medicaid for the 
medical procedures done strictly for research. 
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The cost of the nasal preparation, gargle, and COVID19 initial test will be covered by a grant, there will be
no cost to you
•
The cost of the second COVID19 test if medically indicated due to symptoms may be paid by your
insurer if you are insured by a health insurance company (you should ask your insurer if you have
any questions regarding your insurer’s willingness to pay these costs); or
•
The cost of the second COVID19 test if medically indicated due to symptoms may be paid by Medicare or
Medicaid if you are covered by Medicare or Medicaid. (If you have any questions regarding
Medicare/Medicaid coverage you should contact Medicare by calling 1-800-Medicare (1-800-633-4227)
or Medicaid at 1-800-635-2570.)
Your insurer, Medicare, or Medicaid, may agree to pay for the costs. However, a co-payment or deductible may 
be needed from you. The amount of this co-payment or deductible may be costly. 
WHO WILL SEE THE INFORMATION THAT YOU GIVE? 
When we write about or share the results from the study, we will write about the combined information. We will 
keep your name and other identifying information private. 
We will make every effort to prevent anyone who is not on the research team from knowing that you gave us 
information, or what that information is. When you sign up for the study, you will be assigned a serial number and 
your data will only be associated with that number. Your COVID19 testing will be associated with your name, but 
will not be publicly disclosed. Your name will only be associated with your testing status so that we can alert you 
to the results. If you test positive for COVID19, we will refer you to the Infection Prevention and Control (IPAC) 
group for further treatment. 
You should know that in some cases we may have to show your information to our infection control group at the 
hospital because of the pandemic currently affecting the United States. 
For example, the law may require us to share your information with: 
•
a court or agencies, if you have a reportable disease/condition;
•
authorities, if you report information about a child being abused; or if you pose a danger to yourself or
someone else.
We will be using REDCap a data collection software. It is important to note that any data collection process 
undertaken through the use of third-party software comes with potential risks. Included among these risks is a 
potential breach of confidentiality. The study team will take all available precautions to prevent this from occurring, 
although we cannot guarantee that your identity will never become known. 
We will make every effort to safeguard your data, but as with anything online, we cannot guarantee the security of 
data obtained by way of the Internet. Third-party applications used in this study may have Terms of Service and 
Privacy policies outside of the control of the University of Kentucky. 
REDCap is a secure, web-based program to capture and store data at the University of Kentucky. We will make 
every effort to safeguard your data in REDCap. However, given the nature of online surveys, we cannot 
guarantee the security of data obtained by way of the Internet. 
WHAT IF I WITHDRAW FROM THE STUDY EARLY? 
You can choose to leave the study at any time. You will not be treated differently if you decide to stop taking part 
in the study. 
If you choose to leave the study early, data collected until that point will remain in the study database and may not 
be removed. 
The investigators conducting the study may need to remove you from the study. You may be removed from the 
study if: 
•
you are not able to follow the directions,
•
we find that your participation in the study is more risk than benefit to you, or
•
the agency paying for the study chooses to stop the study early for a number of scientific reasons.
The study intervention will no longer be provided to you and may not be available for purchase. This may occur 
for a number of reasons. 
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ARE YOU PARTICIPATING, OR CAN YOU PARTICIPATE, IN ANOTHER RESEARCH STUDY AT THE SAME 
TIME AS PARTICIPATING IN THIS ONE? 
You may take part in this study if you are currently involved in another research study as long as it does not 
involve other types of nasal preparations. It is important to let the investigator/your doctor know if you are in 
another research study. You should discuss this with the investigator/your doctor before you agree to participate 
in another research study while you are in this study. 
WHAT HAPPENS IF YOU GET HURT OR SICK DURING THE STUDY? 
If you believe you are hurt or if you get sick because of something that is due to the study, you should call Dr. 
Alexandra E. Kejner, MD FACS or Dr. Zachary Porterfield, MD PhD immediately at 859-257-5097. 
It is important for you to understand that the University of Kentucky does not have funds set aside to pay for the 
cost of any care or treatment that might be necessary because you get hurt or sick while taking part in this study. 
Also, the University of Kentucky will not pay for any wages you may lose if you are harmed by this study. 
Medical costs related to your care and treatment because of study-related harm 
•
will be your responsibility;
•
may be paid by your insurer if you are insured by a health insurance company (you should ask your
insurer if you have any questions regarding your insurer’s willingness to pay under these circumstances);
or
•
may be paid by Medicare or Medicaid if you are covered by Medicare or Medicaid (If you have any
questions regarding Medicare/Medicaid coverage you should contact Medicare by calling 1-800-Medicare
(1-800-633-4227) or Medicaid 1-800-635-2570.).
A co-payment/deductible may be needed by your insurer or Medicare/Medicaid even if your insurer or 
Medicare/Medicaid has agreed to pay the costs. The amount of this co-payment/deductible may be costly. 
You do not give up your legal rights by signing this form. 
Due to the coronavirus public health emergency, the federal government has issued an order that may limit your 
right to sue if you are injured or harmed while participating in this COVID-19 study.  If the order applies, it limits 
your right to sue and recover losses from the researchers, healthcare providers, any study sponsor, distributor or 
manufacturer involved with the study. However, the federal government has a program that may provide 
compensation to you or your family if you experience serious physical injuries or death. To find out more about this 
“Countermeasures Injury Compensation Program” please go to https://www.hrsa.gov/cicp/about/index.html or call 
1-855-266-2427
WILL YOU RECEIVE ANY REWARDS FOR TAKING PART IN THIS STUDY? 
You will not receive any rewards or payment for taking part in the study. 
WHAT IF NEW INFORMATION IS LEARNED DURING THE STUDY THAT MIGHT AFFECT YOUR DECISION 
TO PARTICIPATE? 
We will tell you if we learn new information that could change your mind about staying in the study. We may ask 
you to sign a new consent form if the information is provided to you after you have joined the study. 
WILL YOU BE GIVEN INDIVIDUAL RESULTS FROM THE RESEARCH TESTS? 
Do you give permission for us to contact you about research results or incidental findings that are determined to 
be important to you/your family’s health? (Incidental findings are unforeseen findings discovered during the 
course of the research that may affect you or your family’s health). 
□Yes □No
Initials 
You may also withdraw your consent to be contacted with information about research results or incidental 
findings by sending a written request to Dr. Alexandra E. Kejner, MD at 740 S. Limestone Rd E300E 
Kentucky Clinic, Lexington, KY 40502 
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WILL WE CONTACT YOU WITH INFORMATION ABOUT PARTICIPATING IN FUTURE STUDIES? 
We will send a follow up survey up to 6 months following your participation.  This will be linked only to your 
uniquename and will not have any identifiable information.  It will not be shared.
WHAT ELSE DO YOU NEED TO KNOW? 
If you volunteer to take part in this study, you will be one of about 300 people to do so. 
An internal grant is providing financial support and/or material for this study. 
The information or specimens that you are providing will no longer belong to you. The research may lead to new 
clinical or educational knowledge, tests, treatments, or products. These products could have some financial value. 
There are no plans to provide financial payment to you or your relatives if this occurs. 
A description of this clinical trial will be available on ClinicalTrials.gov as required by U.S. Law. This 
website will not include information that can identify you. At most, the website will include a summary of 
the results. You can search this website at any time. 
WILL YOUR INFORMATION (OR SPECIMEN SAMPLES) BE USED FOR FUTURE RESEARCH? 
All identifiable information (e.g., your name, medical record number, or date of birth) will be removed from the 
information or samples collected in this study. This means that no link or code to your identity will be 
kept. After all identifiers have been removed, the information or samples may be used for future research or 
shared with other researchers without your additional informed consent. Once you give your permission to 
have your de-identified information or samples stored, they will be available indefinitely and cannot be 
removed due to the inability to identify them. 
INFORMED CONSENT SIGNATURES 
This consent includes the following: 
•
Key Information Page
•
Detailed Consent
You will receive a copy of this consent form after it has been signed. 
Date
Printed name of [authorized] person obtaining informed consent 
Printed name of research subject
Date 
Signature of research subject 
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