Clinical trial NCT04146116
Conditions: Surgical Site Infection
Keywords: nasal decolonization Orthopedic trauma surgery
Sponsor: University of Iowa
Start date: 2020-02-19; Completion date: 2021-06-08
Enrollment: 65 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Many surgical site infections are caused by bacteria that is transferred from a patient's nose to their open surgical wound. Some small studies have shown that putting povidone-iodine in a patient's nose reduces this risk. This study aims to evaluate the real-world effectiveness of nasal povidone-iodine (PROFEND®) in a group of 50 patients at the University of Iowa.

Detailed description:
Aim 1. Evaluate the real-world effectiveness of intranasal povidone-iodine (PROFEND®) in reducing Staphylococcus aureus colonization and surgical site infections (SSIs).

Aim 1a. Evaluate patients after surgery to determine S. aureus colonization and to survey patients on tolerability of intranasal povidone-iodine decolonization. The intranasal povidone-iodine swab will be administered to the patient's nares around one hour prior to the first surgical incision. It will then be re-applied around 12 hours later, for a total of two applications within a 24 hour period.

During the same visit at 24 hours after surgery, patients will also be administered a questionnaire to determine the tolerability of intranasal povidone-iodine decolonization. Questions will be asked about adverse events (e.g., itching, irritation) and how intranasal povidone-iodine felt (very pleasant, pleasant, neutral, unpleasant, very unpleasant).

Based on the data obtained from this aim, we will summarize the patient acceptance of intranasal povidone-iodine.

Aim 1b. Compare the rates of SSI among orthopaedic trauma surgery patients who received intranasal povidone-iodine to similar patients who received orthopedic trauma surgery before intranasal povidone-iodine implementation.

Arms: arm 1: Intranasal povidone-iodine (PDI PROFEND) will be applied to the patients' noses before orthopedic trauma surgery and after surgery. This intranasal povidone-iodine was developed under the Tentative Final Monograph for Health-Care Antiseptic Drug Products 21 CFR Parts 333 and 369 (Docket # 75N-183H), Federal Register Volume 59, Number 116, Friday, June 17, 1994, Proposed Rules. However, the product need not be controlled like a pharmaceutical drug. The product may be stored and controlled similarly to an iodine or alcohol skin preparation product.
Interventions: intervention 1: intranasal povidone-iodine
Intervention descriptions: intervention 1: povidone-iodine USP, 10% w/w antiseptic

Protocol documents:
ICF_001.pdf: 
Feasibility of Povidone Iodine Decolonization among 
Orthopedic Trauma Surgery Patients 
NCT 201812801 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 1 of 6 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
Feasibility of Povidone Iodine Decolonization among Orthopedic Trauma Surgery 
Patients  
 
Principal Investigator: 
Marin Schweizer 
 
Research Team Contact: 
Marin Schweizer 319-338-0581 extension 3831 
Loreen Herwaldt (319) 356-8150 
 
Sandra Cobb (319) 353-6247 
 
Michael Willey (319) 356-2256  
 
This consent form describes the research study to help you decide if you want to participate.  This form 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights as a research subject.   
• If you have any questions about or do not understand something in this form, you should ask 
the research team for more information.   
• You should discuss your participation with anyone you choose such as family or friends.   
• Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
This is a research study.  We are inviting you to participate in this research study because you are a 
patient at the University of Iowa Hospitals and Clinics and will be having surgery to fix your bones or 
joints (orthopedic trauma). 
 
The purpose of this research study is to evaluate whether PROFEND (an over-the-counter povidone 
iodine antiseptic) can be used to prevent infections among orthopedic trauma patients and patients’ 
opinions about using PROFEND. 
 
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 60 people will take part in this study conducted by investigators at the University of 
Iowa.  
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for approximately 24 hours on the day 
of your surgery or until you are discharged from the University of Iowa Hospitals and Clinics, if 
discharge occurs before 24 hours from surgery. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
1. The research assistant will use a cotton swab to swab the inside of your nostril before your surgery. 
This swab will be tested in the laboratory for Staphylococcus aureus bacteria, which is commonly found 
in people’s noses. 
2. Your nurse will apply PROFEND, a yellow antiseptic ointment, to the inside of your nose in the hour 
before your surgery. 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 2 of 6 
3. After your surgery, in the evening, the research assistant will again use a cotton swab to swab the 
inside of your nose. This swab will be tested for Staphylococcus aureus bacteria. 
4. After your surgery, your nurse will apply a second dose of PROFEND to the inside of your nose, 
timed approximately 12 hours after your first dose. 
5. Approximately 24 hours after your first dose of PROFEND, the research assistant will come to your 
bedside and swab the inside of your nose with a cotton swab. This swab will also be tested for 
Staphylococcus aureus bacteria. This is the last nasal swab we will collect. 
6. The research assistant will ask you to fill out a short questionnaire to tell us about how you felt when 
PROFEND was applied to your nose. You may skip any questions you prefer not to answer. 
7. If you are discharged from the University of Iowa Hospitals and Clinics before the research assistant 
comes to see you approximately 24 hours after your first dose of PROFEND, the research assistant will 
attempt to call you at home by telephone. The research assistant will read the questionnaire over the 
phone to you. You may skip any questions you prefer not to answer or decline to participate in the 
questionnaire.  
8. A research assistant will review your medical record for the following information: medical record 
number, age, date of admission, date of procedure, type and location of procedure, procedure codes, a 
description of your operative site, S. aureus found in nose, other nasal ointments given, antibiotics 
received, date of discharge, where the patient was discharged to, whether the patient developed a 
surgical site infection within 90 days of the procedure, details about the surgical site infection, and death 
within 90 days. This information will be used to determine whether the application of PROFEND has 
been beneficial. 
 
Your information and biospecimens collected as part of the research, even if identifiers will be removed, 
will not be used or distributed for future research studies. Specimens will not be used for commercial 
profit or to complete whole genome sequencing. 
 
WILL I BE NOTIFIED IF MY BIOSPECIMENS RESULT(S) IN AN UNEXPECTED FINDING?   
The results from the nasal swab we collect in this research study are not the same quality as what you 
would receive as part of your routine health care. The nasal swab culture results will not be reviewed by 
a physician who normally reads such results. Due to this, you will not be informed of any unexpected 
findings. The results of your nasal swab culture will not be placed in your medical record with your 
primary care physician or otherwise. If you believe you are having symptoms that may require care, you 
should contact your primary care physician. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
Rare (less than 10%) – 1 to 2% of people who have used PROFEND reported the following side 
effects: 
• Itching (pruritus) 
• Slight burning feeling in the nose 
• Cough 
• Runny nose (rhinorrhea) 
• Skin rash 
Profend has a mild medicinal/iodine scent. 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 3 of 6 
There is also a risk of loss of confidentiality of data.  Measures in place to protect confidentiality are 
indicated in the ‘What About Confidentiality’ section below. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
 
We don’t know if you will benefit from being in this study. 
 
However, we hope that, in the future, other people might benefit from this study because use of 
PROFEND may help prevent infections after the surgical repair of broken bones. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, other options may be available to you.  Instead of 
being in this study, you could request that your physician order a Staphyloccocus aureus nasal screening 
swab and, if that result is positive, prescribe mupirocin, a different ointment that can treat S. aureus 
nasal colonization. The PROFEND product used in this study is only available through participation in 
this study because the product has been donated by the manufacturer. 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
You will not have any additional costs for being in this research study. 
             
WILL I BE PAID FOR PARTICIPATING? 
You will not be paid for being in this research study.   
 
WHO IS FUNDING THIS STUDY? 
PDI Healthcare is funding this research study.  This means that the University of Iowa is receiving 
payments from PDI Healthcare to support the activities that are required to conduct the study.  No one 
on the research team will receive a direct payment or increase in salary from PDI Healthcare for 
conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
• If you are injured or become ill from taking part in this study, medical treatment is available at the 
University of Iowa Hospitals and Clinics. 
• The University of Iowa does not plan to provide free medical care or payment for treatment of any 
illness or injury resulting from this study unless it is the direct result of proven negligence by a 
University employee.  
• If you experience a research-related illness or injury, you and/or your medical or hospital insurance 
carrier will be responsible for the cost of treatment. 
 
WHAT ABOUT CONFIDENTIALITY? 
We will keep your participation in this research study confidential to the extent permitted by law.  
However, it is possible that other people such as those indicated below may become aware of your 
participation in this study and may inspect and copy records pertaining to this research.  Some of these 
records could contain information that personally identifies you.  
• federal government regulatory agencies,  
• the U.S. Food and Drug Administration and the sponsor, PDI Healthcare,   
• auditing departments of the University of Iowa, and  


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 4 of 6 
• the University of Iowa Institutional Review Board (a committee that reviews and approves 
research studies)  
  
In the future, PDI Healthcare may continue to use your health information that is collected as part of this 
study. For example, PDI Healthcare may combine information from this study with the results of other 
studies to re-analyze the safety and effectiveness of the study medication, to evaluate other products or 
therapies, to develop a better understanding of a disease, or to improve the design of future research 
studies. PDI Healthcare may also share information from the study with regulatory agencies in foreign 
countries. 
 
To help protect your confidentiality, we will use a descriptor such as “P01-MMDD” (MM: numerical 
month, DD: numerical day) to label any data, documents, or specimens. Your name or other identifying 
information will not be used. The hard copy records (the survey and consent form) will be a locked 
cabinet inside a locked office. The medical record collected will be stored in a password-protected, 
access-restricted shared network drive that is only accessible by members of the research team. The 
nasal swabs will be destroyed after any cultures grow and the results will be stored with in the network 
drive as well.  If we write a report or article about this study or share the study data set with others, we 
will do so in such a way that you cannot be directly identified. 
 
The University of Iowa Hospitals and Clinics generally requires that we document your participation in 
research occurring in a University of Iowa Health Care facility.  This documentation will be in either 
your medical record or a database maintained on behalf of the institution reflecting that you are 
participating in this study. The information included will provide contact information for the research 
team as well as information about the risks associated with this study. We will keep this Informed 
Consent Document in our research files; it will not be placed in your medical record chart. 
 
A description of this clinical trial will be available on http://www.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 MY HEALTH INFORMATION BE USED DURING THIS STUDY? 
The Federal Health Insurance Portability and Accountability Act (HIPAA) requires your health care 
provider to obtain your permission for the research team to access or create “protected health 
information” about you for purposes of this research study.  Protected health information is information 
that personally identifies you and relates to your past, present, or future physical or mental health 
condition or care.  We will access or create health information about you, as described in this document, 
for purposes of this research study and for your treatment.  Once your health care provider has disclosed 
your protected health information to us, it may no longer be protected by the Federal HIPAA privacy 
regulations, but we will continue to protect your confidentiality as described under “Confidentiality.” 
 
We may share your health information related to this study with other parties including federal 
government regulatory agencies, the University of Iowa Institutional Review Boards and support staff, 
or the study sponsor PDI Healthcare. 
 
You cannot participate in this study unless you permit us to use your protected health information.  If 
you choose not to allow us to use your protected health information, we will discuss any non-research 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 5 of 6 
alternatives available to you.  Your decision will not affect your right to medical care that is not 
research-related.  Your signature on this Consent Document authorizes your health care provider to give 
us permission to use or create health information about you. 
 
Although you may not be allowed to see study information until after this study is over, you may be 
given access to your health care records by contacting your health care provider. Your permission for us 
to access or create protected health information about you for purposes of this study has no expiration 
date. You may withdraw your permission for us to use your health information for this research study by 
sending a written notice to Dr. Marin Schweizer, Institute for Clinical and Translational Science, 
200 Hawkins Dr, Iowa City, IA, 52242.   However, we may still use your health information that was 
collected before withdrawing your permission.  Also, if we have sent your health information to a third 
party, such as the study sponsor, or we have removed your identifying information, it may not be 
possible to prevent its future use.  You will receive a copy of this signed document. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time.  If you decide not to be in this 
study, or if you stop participating at any time, you won’t be penalized or lose any benefits for which you 
otherwise qualify. 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact: Sandra Cobb (319) 353-6247. If you experience a research-related injury, please contact: 
Loreen Herwaldt (319) 356-8150.  
 
If you have questions, concerns, or complaints about  your rights as a research subject or about research 
related injury, please contact the Human Subjects Office, 105 Hardin Library for the Health Sciences, 
600 Newton Rd, The University of Iowa, Iowa City, IA  52242-1098, (319) 335-6564, or e-mail 
irb@uiowa.edu.  General information about being a research subject can be found by clicking “Info for 
Public” on the Human Subjects Office web site, http://hso.research.uiowa.edu/. To offer input about 
your experiences as a research subject or to speak to someone other than the research staff, call the 
Human Subjects Office at the number above. 
 
 
This Informed Consent Document is not a contract. It is a written explanation of what will happen 
during the study if you decide to participate. You are not waiving any legal rights by signing this 
Informed Consent Document. Your signature indicates that this research study has been explained to 
you, that your questions have been answered, and that you agree to take part in this study.  You will 
receive a copy of this form. 
 
 
 
 
 
 
 
 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201812801 
APPROVAL DATE: 10/16/19 
 
 
 
Page 6 of 6 
 
Subject's Name (printed):  __________________________________________________________ 
 
 
 
 
__________________________________________ 
_______________________________ 
(Signature of Subject)  
 
 
 
 
(Date) 
 
 
Statement of Person Who Obtained Consent 
 
I have discussed the above points with the subject or, where appropriate, with the subject’s legally 
authorized representative.  It is my opinion that the subject understands the risks, benefits, and 
procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 

Prot_002.pdf: 
Title: Feasibility of Pre-operative Povidone Iodine Decolonization among Orthopedic 
Trauma Surgery Patients To Reduce S. aureus SSIs  
NCT Number: NCT04146116 
July 18, 2019  


Background  
Our previous multicenter study of a bundled intervention to prevent S. aureus surgical site 
infections (SSI) resulted in a 42% decrease in complex S. aureus SSIs (rate ratio = 0.58; 95% 
CI, 0.37 to 0.92) among hip, knee and cardiac surgery patients.1 The evidence-based bundled 
intervention included screening for S. aureus nasal colonization, decolonizing carriers with 
intranasal mupirocin and chlorhexidine gluconate body wash, and prescribing optimal 
perioperative antibiotics. However, even among elective orthopedic procedures, compliance 
with this intervention was less than ideal.  
 
Decolonization interventions such as this have not been rigorously investigated in trauma 
surgery populations, because of the expeditious and non-elective nature of trauma care. Pre-
operative decolonization with mupirocin is impractical to complete in the vast majority of patients 
with orthopaedic trauma. Dr. Michael Willey, an orthopaedic trauma surgeon, went to great 
lengths to implement S. aureus screening and mupirocin decolonization of carriers among his 
patient population at University of Iowa Hospitals and Clinics (UIHC). Yet, even with full surgeon 
support, compliance with S. aureus nasal screening was 80% and compliance with mupirocin 
was only 41%. Thus, there is great interest in determining whether a simpler intervention using 
povidone-iodine (PROFEND®) nasal decolonization could be implemented into the clinical 
process of care and reduce rates of surgical site infections (SSI) in this very high-risk 
population.  
 
PROFEND® nasal decolonization has the potential to be an efficient and low-cost intervention 
to reduce rates of SSI.2,3 Although orthopaedic trauma patients are at high risk of SSI, our 
sample size and power calculations found that a study evaluating the effectiveness of nasal 
PROFEND® for reducing deep SSI in this population would need ~1,000 patients, and thus 
would require participation by multiple hospitals. A pilot study evaluating the feasibility of 
administering PROFEND® among patients undergoing orthopaedic trauma procedures could 
inform the development and implementation of a large, multicenter study.  
 
This proposal describes a small, phase IV post-marketing study to assess the best way to 
implement this FDA approved product among surgical patients.  
 
Study design  
Implement PROFEND® pre-operative decolonization for individuals undergoing operative 
fixation of lower extremity fractures and evaluate the feasibility of this intervention.  
Aim 1. Evaluate patients 24 hours after surgery to determine S. aureus colonization and 
to survey patients on tolerability of PROFEND® decolonization.  
 
Patients will be tested for S. aureus nasal colonization prior to surgery, the evening after surgery 
and on the day after surgery. At each time point, a dry, sterile, rayon swab will be used to 
sample the anterior apex portion of the right and left nostril. The swab will be immersed in a 
tube of 1 mL neutralizing solution (75 mM phosphate buffer containing 1.0% lecithin, 0.1% 
Triton™ X-100, 5.0% polyoxyethylene sorbitan monooleate, and 0.5% sodium thiosulfate, pH 
7.9 + 0.1) and capped tightly. The swabs will be inoculated into 1mL broth and vortexed for 15 
seconds. Serial dilutions will be performed and plated on media. The cultures will be 
quantitatively assessed to determine the log10 reduction in S. aureus after use of PROFEND®. 
For semi-quantitative cultures the swabs will be inoculated into 5mL broth, incubated with 
agitation overnight for a broth enrichment step. After 24 hours, 10uL will be plated onto the first 
quadrant of the media and each successive quadrant will be streaked using a new bacteriologic 
loop in order to dilute the number of bacteria in each quadrant. The culture results will provide 
information we will need when designing a large multicenter study of PROFEND®. The 


PROFEND® swab will be administered to the patient’s nares following this initial sample around 
one hour prior to the first surgical incision. It will then be re-applied around 12 hours later, for a 
total of two applications within a 24 hour period.  
 
During the same visit at 24 hours after surgery, patients will also be administered a 
questionnaire to determine the tolerability of PROFEND® decolonization. Questions will be 
asked about adverse events (e.g., itching, irritation) and how PROFEND® felt (very pleasant, 
pleasant, neutral, unpleasant, very unpleasant). The adverse event question will be the same as 
a question that we have already asked 183 patients who received mupirocin. Thus, we will be 
able to compare these results with one another.  
 
Based on the data obtained from this aim, we will summarize the patient acceptance of 
PROFEND®.  
 
 
References  
1. Schweizer ML, Chiang HY, Septimus E, et al. Association of a bundled intervention with surgical site 
infections among patients undergoing cardiac, hip, or knee surgery. JAMA : the journal of the American 
Medical Association. 2015;313(21):2162-2171.  
2. Bebko SP, Green DM, Awad SS. Effect of a Preoperative Decontamination Protocol on Surgical Site 
Infections in Patients Undergoing Elective Orthopedic Surgery With Hardware Implantation. JAMA 
surgery. 2015.  
3. Phillips M, Rosenberg A, Shopsin B, et al. Preventing surgical site infections: a randomized, open-label 
trial of nasal mupirocin ointment and nasal povidone-iodine solution. Infection control and hospital 
epidemiology : the official journal of the Society of Hospital Epidemiologists of America. 2014;35(7):826-
832.