Effect of Expanding Barrier Precautions for Reducing Clostridium Difficile Acquisition in VA
Phase: NA
Conditions: Clostridium Difficile
Sponsor: VA Office of Research and Development

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Effect of Expanding (Gloving) Barrier Precautions for Reducing Clostridium 
difficile Acquisition (and Infection) in VA: The GLORI Study 
Funding Agency: VA HSR&D 
Principal Investigator: Nasia Safdar, MD, 
PhD 
Version 11.0 
March 26, 2024 

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Version 11.0 
March 26, 2024 
Abstract 
Clostridium difficile infection (CDI) has become the most common healthcare-associated 
infection (HAI) in U.S. hospitals, causing half a million infections and 30,000 deaths annually. 
CDI ranges from asymptomatic colonization, mild to severe diarrhea, pseudomembranous 
colitis, toxic megacolon, colonic perforation, and death. Risk factors for CDI include older age, 
comorbidity, hospitalization, exposure to others with CDI, and antibiotic use. Prevention of 
healthcare-onset (HO)-CDI has become a priority for hospitals. Hospital prevention measures 
are limited to modifiable risk factors (i.e., prudent antibiotic use and limiting exposure to C. 
difficile). Hospital exposure to C. difficile can occur directly (i.e., hands or clothing of healthcare 
workers) or indirectly (i.e., environmental surfaces or shared equipment) so infection 
prevention measures focus on healthcare worker hand hygiene and barrier precautions (i.e., 
use of gowns and gloves) and cleaning and disinfection of the hospital environment. However, 
these interventions are limited to symptomatic patients who test positive for CDI. 
Asymptomatic patients serve as a reservoir for cross-contamination, but microbiological 
screening for asymptomatic carriage of C. difficile is not routinely performed in healthcare. 
Gloving for all patient contacts may interrupt transmission from asymptomatic patients 
colonized with C. difficile. 
The overall purpose of the study is to determine the effectiveness of healthcare worker use of 
gloves for all patient contact for reducing acquisition of C. difficile and HO-CDI in inpatient 
hospital units. The main objective of the study is to compare the effects of universal gloving for 
all patient contact to the current standard of care (i.e., glove and gown use only for known CDI 
cases). The aims of the study are: 
1) Compare the effects of universal gloving for all patient contact to the current standard 
of care on C. difficile acquisition rates in hospitalized patients; 
2) Compare the effects of universal gloving compared to standard of care gloving on CDI 
rates, other HAIs, 30-day mortality, and unit length of stay; and 
3) Describe intervention fidelity, cost, and stakeholder (patients’ and healthcare 
workers’) experiences with universal gloving. 
The study will be a cluster randomized trial (CRT) in ten inpatient VA hospital units. Units will be 
randomized either to implement barrier precautions for all patient contacts (universal gloving 
intervention) or continue standard of care (barrier precautions for patients with known CDI and 
other antibiotic-resistant organisms). The intervention will consist of all healthcare workers 
(nurses, providers, respiratory therapists, radiology/laboratory technicians, etc.) utilizing gloves 
for all patient contacts in the units randomized to receive the intervention. Unit-level data, 
including C. difficile acquisition and infection rates, mortality, length of stay, and barrier 
precaution compliance, will be collected monthly from all participating sites. 
If universal gloving is found to be effective in reducing C. difficile acquisition and subsequent 
infection (and its associated morbidity, mortality, and costs), the results will change the 
paradigm for CDI prevention in healthcare settings. 
 
 
 
 
 
 
 
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Page 2 of 35 

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List of Abbreviations 
 
AE 
Adverse Event 
CAUTI 
Catheter-associated Urinary Tract Infection 
CDC 
Centers for Disease Control and Prevention 
CDI 
Clostridium difficile infection 
CLABSI 
Central Line-associated Bloodstream Infection 
CP 
Contact Precautions 
CRT 
Cluster Randomized Trial 
CTSP 
Centralized Transcription Services Program 
HAI 
Healthcare-associated Infection 
HIPAA 
Health Information Portability and Accountability Act 
HO-CDI 
Hospital Onset-Clostridium difficile Infection 
ICU 
Intensive Care Unit 
IPEC 
Inpatient Evaluation Center 
IRB 
Institutional Review Board 
LAR 
Legally Authorized Representative 
LSI 
Local Site Investigator 
MDRO 
Multidrug-Resistant Organism 
MRSA 
Methicillin-Resistant Staphylococcus aureus 
PCR 
Polymerase Chain Reaction 
PHI 
Personal Health Information 
PI 
Principal Investigator 
PII 
Personally Identifying Information 
RA 
Research Assistant 
SAE 
Serious Adverse Event 
VA 
Department of Veterans Affairs 

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Contents 
1.0 
Study Personnel .............................................................................................................6 
2.0 
Introduction ....................................................................................................................6 
3.0 
Objectives ......................................................................................................................8 
4.1 
Resources and Personnel ................................................................................................8 
4.2 Participating Sites 
. .......................................................................................................................................... 8 
4.3 Personnel 
. .......................................................................................................................................... 9 
4.4 Resources 
. .......................................................................................................................................... 9 
5.1 
Study Procedures........................................................................................................ 10 
5.2 Study Design 
. ........................................................................................................................................ 10 
5.2.1 
Experimental Design .......................................................................................... 10 
5.2.2 
Intervention ....................................................................................................... 11 
5.2.3 
Study Population............................................................................................... 11 
5.2.4 
Risk Analysis .................................................................................................... 11 
5.3 Recruitment Methods .................................................................................................... 13 
5.4 Informed Consent Procedures........................................................................................ 16 
5.4.1 Consent Procedures and Documentation................................................................. 17 
5.5 Inclusion/Exclusion Criteria ............................................................................................ 18 
5.6 Study Evaluations ......................................................................................................... 19 
5.7 Safety Monitoring.......................................................................................................... 23 
5.8 Data Analysis ............................................................................................................... 23 
5.8.1 Sample Size Determination .................................................................................... 23 
5.8.2 Statistical Analyses ................................................................................................. 24 
5.9 Withdrawal of Subjects.................................................................................................. 25 
6.1 
Reporting .................................................................................................................... 25 
7.1 
Privacy and Confidentiality ........................................................................................... 27 

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7.2 Specimen Banking 
. ........................................................................................................................................ 29 
8.0 
Communication Plan ....................................................................................................29 
9.0 
References .................................................................................................................31 

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1.0 
Study Personnel 
 
Principal Investigator: 
Nasia Safdar, MD, PhD – Associate Chief of Staff for Research, Madison VA 
Nasia.Safdar@va.gov 
Co-Investigators: 
Christopher Crnich, MD, PhD – Chief of Medicine, Hospital Epidemiologist, Madison VA 
Christopher.Crnich@va.gov 
Linda McKinley, RN, BSN, MPH – Research Health Scientist, Madison VA 
Linda.McKinley2@va.gov 
Charlesnika Evans, PhD, MPH – Research Health Scientist, Co-Director of CARRIAGE, 
Hines VA 
Charlesnika.Evans@va.gov 
 
Amy Weintrob, MD – Medical Center Epidemiologist, Washington DC VA 
Amy.Weintrob@va.gov 
Collaborators: 
Daniel Morgan, MD, MS – Chief Hospital Epidemiologist, Baltimore VA 
Daniel.Morgan2@va.gov 
Louise Dembry, MD, MS, MBA – Chief/Director of Hospital Epidemiology/Infection 
Prevention, VA Connecticut Healthcare System 
Louise.Dembry@va.gov 
 
 
Susan Zickmund, PhD – Research Scientist, Director of CTSP, Salt Lake City VA 
Susan.Zickmund@va.gov 
Jiwei Zhao, PhD – Biostatistician, University of Wisconsin – Madison 
Helene Moriarty, BSN, MSN, PhD – Nurse Researcher, Villanova University 
helene.moriarty@villanova.edu 
Coordinating Site (Madison VA) Personnel: 
Julie Keating, PhD – Research Health Scientist 
Madison VA 
Julie.Keating@va.gov 
 
Cara Ray, MA – Regulatory Specialist 
Madison VA 
 Cara.ray@va.gov 

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Kelsey Baubie, MS, MPH – Study Coordinator 
Madison VA 
Kelsey.Baubie@va.gov 
 
Jared Godfrey, BS – Lab Supervisor 
Madison VA 
Jared.Godfrey@va.gov 
 
Local Site Investigators 
Charlesnika Evans, PhD, MPH – Research Health Scientist, Co-Director of CARRIAGE, 
Hines VA 
Charlesnika.Evans@va.gov 
Amy Weintrob, MD – Medical Center 
Epidemiologist, Washington DC VA 
Amy.Weintrob@va.gov 
 
Christopher Pfeiffer, MD – Medical Center Epidemiologist 
Portland VA 
Christopher.Pfeiffer2@va.gov 
 
Mary Hagle, RN, PhD – Nurse Scientist 
Milwaukee VA 
Mary.Hagle@va.gov 
Michael Gelman, MD, PhD – Medical Director of Infection Control Program 
Bronx VA 
Michael.Gelman@va.gov 
 
 
2.0 
Introduction 
Clostridium difficile is the major infectious cause of healthcare-associated diarrhea, causing as 
many as 25% of cases. 1-3 C. difficile infection (CDI) affects 500,000 Americans each year, is 
responsible for 29,000 deaths annually, and has an estimated annual cost of $ 1.1 billion in the 
US. 4,5 Prevention of CDI is essential, and is a critical patient safety issue.4,6-8 Transmission of 
highly antimicrobial-resistant C. difficile occurs primarily in healthcare facilities, where studies 
have found C. difficile acquisition in 1–13% of patients hospitalized for less than a week and in 
50% of patients hospitalized for more than 4 weeks. 9,10 Containment of CDI has been 
designated a public health priority by several federal agencies, including the VA. 11,12 
Based on evidence-based guidelines from the Infectious Diseases Society of America, the VA 
Multidrug Resistant Organism (MDRO) Program Office developed and mandated a multifaceted 
national bundle for prevention of CDI at VA facilities in 2012 which includes: 13 1) rapid, 
appropriate diagnostic testing for C. difficile, 2) empiric isolation for patients with diarrhea and 
suspected CDI, 3) contact isolation for patients with confirmed CDI, 4) environmental 
decontamination of rooms of patients with CDI, and 5) strategies for improving healthcare 
worker hand hygiene. However, decreases in CDI rates have been modest, variable and 
inconsistent.14 A major reason for this finding is that these interventions are limited to 
symptomatic patients who test positive for CDI. This is a gap because asymptomatic patients 
are a major reservoir of C. difficile, colonization greatly increases the risk of infection and 

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importation of CDI from the community to the hospital is increasing.15,16 Yet, there is a paucity of 
evidence on how to reduce transmission from asymptomatic patients. 
The two main potential approaches to tackling transmission from the reservoir of colonized 
patients are to undertake regular microbiological screening or to implement universal contact 
precautions. The efficacy of these approaches is yet unknown. Microbiological screening at 
admission to detect asymptomatic carriage of C. difficile and place colonized patients in 
contact precautions is not favored by front-line healthcare workers because it is costly, labor- 
intensive and requires microbiology resources at each site. Universal gloving where healthcare 
workers don gloves upon each entry to a patient room regardless of disease state may be 
promising in reducing the acquisition of CDI because gloves are the most effective means of 
preventing hand contamination with C. difficile spores. Data on universal gowning and gloving 
is limited to organisms other than C. difficile and in ICU settings which cannot be extrapolated 
to C. difficile because C. difficile is a spore-forming organism allowing it to remain viable in 
adverse conditions in the environment for long periods of time and diarrhea leads to heavy, 
persistent environmental contamination.17-20 We hypothesize that current standard of practice 
that targets glove use for only patients with known CDI does not interrupt C. difficile 
transmission from patients with asymptomatic colonization resulting in C. difficile acquisition 
and subsequent infection. The rationale for the hypothesis is that both patients with active 
infections and those with asymptomatic colonization serve as reservoirs for patient-to-patient 
transmission of C. difficile either through contaminated healthcare workers hands or 
contaminated healthcare environment (i.e., patient equipment and/or environmental surfaces). 
Hand and environmental contamination with C. difficile spores are well established and these 
spores are resistant to both hand hygiene and environmental antisepsis methods21-23. 
 
Hand hygiene is generally accepted to be the most effective means of infection prevention, and 
current guidance recommends the use of the preferential use of alcohol based hand rubs 
(ABHR) over soap and water in all clinical situations except 1) when hands are visibly soiled 
(e.g., blood, body fluids) and 2) after caring for a patient with known or suspected C. difficile or 
norovirus during an outbreak or if endemic rates are high.24 C. difficile spores are not killed by 
ABHR and may be difficult to remove even with thorough hand washing with soap and water.21,22 
Strict adherence to gloving is the most effective means of preventing hand contamination with 
C. difficile spores.25 One study prospectively studied the use of gloves in interrupting C. difficile 
transmission26 and universal gloving has been proposed as a novel approach to prevent CDI.27 
 
Of the two possible approaches to target colonization, screening patients for asymptomatic 
carriage has increased costs, need for microbiology resources and training, and increased use 
of contact precautions for those colonized. Universal gloving also results in increased use of 
contact precautions by gowning and gloving, but the microbiology resources are not necessary. 
In discussions with VA facilities, there has been much enthusiasm for universal gloving and 
none for screening and isolation. 
 
3.0 
Objectives 
The overall goal of our research is to reduce CDI. This proposed study will study the 
effectiveness of healthcare workers’ use of universal gloving for all patient contact in reducing 
the acquisition of C. difficile in hospitalized patients compared with current VA standard care 
(i.e., healthcare worker glove use when caring for patients in CP isolation) using a pragmatic 
cluster randomized trial (CRT) in ten inpatient VA hospital units. 

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We hypothesize that patients with asymptomatic carriage of C. difficile can shed the pathogen 
and therefore are an important reservoir for transmission of C. difficile. There are two 
approaches to target this colonization: microbiological screening of patients to identify those 
patients who are carriers of C. difficile and increased barrier precautions. Microbiological 
screening for asymptomatic carriage of C. difficile is not routinely performed in healthcare 
because data is limited regarding the use of a detection and isolation intervention to decrease 
transmission of C. difficile and therefore not recommended at present.28 Here, we propose to 
implement the use of gloves for all patient contact (i.e., universal gloving) in non-ICU acute care 
units to prevent transmission of C. difficile from both patients with known infections and those 
patients who are asymptomatic carriers. 
We have proposed three objectives: 
• 
To compare the effects of universal gloving for all patient contact to the current standard 
of care on C. difficile acquisition rates in hospitalized patients 
• 
To compare the effects of universal gloving compared to standard of care on CDI rates, 
other healthcare-associated infections (CLABSI, CAUTI, MRSA), 30-day mortality and 
unit length of stay. 
• 
To evaluate intervention fidelity (hand hygiene and barrier precaution compliance; glove 
use for all patients and glove plus gown use for patients in contact precautions (CP) 
isolation), the cost and stakeholder experiences (interviews and provider-patient contact 
survey). 
This study will be the first to evaluate whether universal gloving will prevent transmission from 
patients who are asymptomatically colonized with C. difficile in non-ICU units in an RCT. The 
study will also investigate the impacts of universal gloving on associated factors, including CDI, 
other healthcare-associated infections, and their effects on a unit’s morbidity, mortality, costs 
and patients and healthcare workers experience. If the results of the study support universal 
gloving, it will change the paradigm for prevention of CDI nationwide. 
 
4.1 
Resources and Personnel 
4.2 
Participating Sites 
The coordinating study site and personnel (including the PI) will be based at the Madison VA. 
The Madison VA-based team will be responsible for overall study execution, including protocol 
refinement, comprehensive site training, medical monitoring, handling of patient-related issues 
that may arise, coordination of clinical event ascertainment efforts, and interfacing with study 
committees and local site teams. 
Five sites (Milwaukee, Hines, Bronx, Washington DC, Portland) will enroll ten inpatient units 
(i.e., acute medical, medical/surgical, surgical or specialty units) to participate in the study; 2 
inpatient units at each site. A Local Site Investigator (LSI; see above list of names under 
personnel) and a Research Assistant (RA) will be assigned to each participating site to assist in 
completing study procedures and ensuring compliance with the study protocol at this site. 
Local site responsibilities will be discussed in detail with the LSI and RA prior to beginning study 
procedures. These responsibilities may include: 
• 
Maintain site documentation (e.g. study binder, study information sheets, sample code 
key) 
• 
Obtain local approvals as required 

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• 
Ensure adherence to study protocol and procedures 
• 
Provide education/training on study procedures for local staff and on-site resource for 
staff and patient questions 
• 
Recruit patients and consent for swab/stool sample collection 
• 
Specimen collection 
o Stool samples – collect swab/stool specimens, 
o provide supplies and instructions to patients performing self-collected 
specimen collection, 
o specimen label, store, ship 
• 
Collect data 
o intervention fidelity 
o Clinical outcomes 
• 
Upload data to Madison 
• 
Recruit patients and healthcare workers for interviews/focus groups 
• 
Facilitate and/or Conduct patient interviews 
• 
Facilitate and/or Conduct healthcare worker focus groups 
• 
Conduct observations of hand hygiene, contact precaution, and universal gloving 
practice compliance 
• 
Recruit patients and healthcare workers for surveys 
• 
Organize survey collection process 
• 
Participate in meetings/check-ins with coordinating site; maintain communication 
• 
Follow all VA privacy/information security regulations 
Clinical staff (such as nursing staff) will also assist with study conduct. Clinical staff’s 
responsibilities may include: 
• 
Inform patients that the unit is participating in a research study and that staff will be 
wearing gloves during all patient care activities. 
• 
Specimen collection 
o Stool samples – collect swab/stool specimens, 
o provide supplies and instructions to patients performing self-collected 
specimen collection, 
o Collect patient self-collected samples, label and store according to sample 
collection guidelines for RA processing 
 
4.3 
Personnel 
The Madison-based study team includes the PI, Co-Investigators, Project Manager/Study 
Coordinator, laboratory staff, and Research Scientists. 
Each participating site will name an LSI and RA to handle local procedures as described above. 
Additional personnel at each site (e.g. unit leadership) will be engaged as needed to ensure 
buy-in and adherence to study procedures. 
4.4 
Resources 
Multiple entities will support the successful progress and completion of the study: 
Executive Committee (EC): The EC will consist of the PI, the site investigators, and the 
research assistants. The EC will review study contact, recruitment and 
troubleshooting, IRB, and other regulatory issues. 

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Steering Committee (SC): The SC will be composed of the PI and co-investigators as 
well as the lead biostatistician. The SC will discuss progress, recruitment goals, review 
quality of the data, and troubleshoot. 
Coordinating Site Committee (CSC): The CSC will be physically located at the Madison 
VA and led by Dr. Nasia Safdar (PI). The CSC will be responsible for overall study 
execution, including protocol refinement, comprehensive site training, medical 
monitoring, handling of patient-related issues that may arise, coordination of clinical 
event ascertainment efforts, and coordinating with other Committees and with VA 
HSR&D. The CSC will also coordinate with statistical and qualitative data experts to 
ensure appropriate data management, quality control and quality assurance, information 
technology for communication and trial conduct monitoring, statistical methods (ex. 
randomization, interim monitoring), analyses, interpretation of findings, preparation of 
results, and publication of findings from the trial. 
We will work with the VA Centralized Transcription Services Program, located at the Salt Lake 
City VA and led by Dr. Susan Zickmund, for the transcription of qualitative interviews. 
 
5.1 
Study Procedures 
5.2 
Study Design 
5.2.1 
Experimental Design 
We will conduct this study using a pragmatic stratified-cluster randomized trial (CRT) in ten 
inpatient VA hospital units (acute medical, medical/surgical, or surgical inpatient acute care 
units). Hospital units will be randomly assigned in a 1:1 ratio: 5 units will be randomized to 
enact universal gloving practices (intervention) and 5 units will continue standard of care 
(control). 
Due to resource and personnel feasibility, randomization will be stratified by location to allow for 
the selection of one intervention and one control unit at each site. 
A 6-12-month pre-intervention period will be used to conduct preliminary work at sites including 
training research assistants, identifying current practices, finalizing monitoring and observation 
plans. Each participating unit will collect data for up to 24 months – a 24-month intervention 
period. During the intervention period, we will collect data on a monthly basis, including C. 
difficile acquisition and infection rates, other infections (CLABSI, CAUTI, MRSA), mortality, 
length of stay, and intervention fidelity (hand hygiene compliance and barrier precaution 
compliance; glove use for all patients and glove plus gown use for patients in CP isolation). 
These unit-level data will be obtained from aggregate reports prepared by the infection control 
department at each site from data they have entered into the VA Inpatient Evaluation Center 
(IPEC) data management system and/or from VA administrative records. Patient-level data on 
relevant clinical characteristics such as comorbidities, prior treatments and healthcare usage, 
and outcomes such as HAIs will be obtained from VA administrative records for patients who 
consent to stool specimen collections. We will conduct interviews/focus groups with healthcare 
workers throughout the intervention period and individual interviews with patients throughout 
the intervention period. These interviews and focus groups will explore healthcare workers’ and 
patients’ experiences with the intervention. We will also conduct patient and healthcare worker 
survey on provider-patient contact using a Likert scale to assess the amount of contact patients 
have with their healthcare workers in both the intervention and control groups. 

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5.2.2 
Intervention 
In the units randomized to receive the intervention, all healthcare workers (nurses, providers, 
respiratory therapist, radiology and laboratory technicians, etc.) will utilize universal gloving 
(non- sterile gloves) for all patient contacts. If a patient in the intervention unit is known to have 
CDI or an MDRO, both gowns and gloves will be used as is current standard of care practice for 
patients in CP isolation. Signage denoting what type of precautions are needed will be placed on 
the door of each patient’s room. 
 
The non-intervention units will follow standard of care which consists of healthcare workers 
following barrier contact precautions (i.e., gloves plus gowns) only for patients with known CDI 
and other MDROs (e.g., MRSA). 
 
5.2.3 
Study Population 
The study population will be ten participating units. All patients aged 18 and above within these 
units will be included in the intervention and clinical data collection. 
Within the units assigned to the intervention, we will conduct interviews with healthcare workers 
and patients about their experiences with the intervention. We will conduct focus groups with up 
to 60 healthcare workers (up to 12 individuals for each of the 5 sites enacting the intervention) 
who are aged 18 and above, are employed by the participating facility and have performed 
employment duties within the participating unit during the intervention period, and who agree to 
participate in the interview. We will interview 50 patients (10 per site enacting the intervention) 
who are aged 18 and above, are admitted as an inpatient to the participating unit during the 
intervention period, and who agree to participate in the interview. 
We will also conduct surveys with patients and environmental services staff. We will aim to 
survey 10 patients per site at all 10 participating sites, for a total of 100 patients (50 from 
intervention group and 50 from control group). Given the small expected number of 
environmental service staff on each unit, we will aim to survey at least 1 worker per site at all 
10 participating sites, for a total of 10 workers. 
Focus groups and patient interviews will be conducted via face-to-face or phone/Teams call. All 
interviews will be audio -recorded to be transcribed later for analysis of themes and concepts 
unless patients decline to be recorded, in which case field notes will be taken and analyzed 
instead. Please see section 7.0 for specific detailed procedures for handling interview recording 
and transcript information. 

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5.2.4 
Risk Analysis 
5.2.4.1 
Known Potential Risks 
This is a minimal risk study to participating units and to the healthcare workers and patients 
within these units. 
Physical Risks. No physical risks are anticipated from this study. Use of barrier contact 
precautions (gloving plus gowning) is currently the standard of care for patients with certain 
communicable diseases including antibiotic-resistant organisms (e.g., MRSA), so the expansion 
of universal gloving for care of all patients (intervention) does not present additional risk to 
healthcare workers or patients. 
There are no physical risks associated with collection of stool samples for C. difficile lab testing. 
However, if we are unable to obtain a stool specimen, we will obtain a stool sample using a 
perirectal swab which may present minimal discomfort or embarrassment to patients. The 
perirectal swabs will be obtained using a CDC standardized methodology and standardized 
specimen collection technique which involves swabbing the perirectal area. Perirectal swabs 

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have been found to be equivalent to rectal swab specimens for detection of asymptomatic 
carriers of C. difficile.29 The swab will be taken from the skin surrounding the anus and will not 
be inserted into the anus. The patient will feel a sensation similar to wiping their bottom with 
toilet paper during the perirectal swab. The swab collection may be associated with 
embarrassment but will be collected using standard of care privacy practices including the use 
of a privacy curtain or closing the door to the patient room. If subject reports embarrassments 
post procedure an assessment of the procedure and review of protocol will be conducted with 
staff. 
If any patient desires to decline perirectal swabs, we will not collect swabs from that individual. 
In these cases, stool samples may be used to measure C. difficile acquisition rather than 
perirectal swabs if the patient agrees. Stool samples will be collected using standard 
procedures and pose no risk to the patient. 
Patients may become tired during interviews and study team members will frequently elicit 
feedback from patients about their ability to continue during the interview. 
Psychological Risks. No psychological risks are expected to result from participating in the 
study, including via interviews, observations, or surveys. Healthcare workers may fear 
repercussions from interviews, observation or survey, but potential participants will verbally 
agree or decline to participate in private without the knowledge of their supervisors to avoid 
potential feelings of coercion or fear of repercussion. Additionally, participating healthcare 
workers will not be subordinate in any way to study team members. There will not be any 
identifiable data collected; anonymity will avoid any possible repercussion and data will not be 
used to assess individual performance at study sites, nor will our data in any way affect 
participant standing at the institution. As part of the interview process, a statement will be read 
prior to audio recording asking the interviewee not to share personal information. Although 
there is no intention to collect identifiable healthcare worker data that would link interview 
responses to a healthcare worker, if identifiable data was inadvertently shared during audio 
recording, this data will be deleted from the transcripts. Participants may experience social or 
psychological discomfort during interviews. Study team members will frequently elicit feedback 
from participants about their comfort level and remind them they do not have to answer 
questions they are not comfortable with and that the entire interview is voluntary. Study 
participation will be entirely voluntary. 
Social, Legal, or Other Risks. There is a minimal risk of loss of privacy or confidentiality. Only 
the minimum necessary identifiers will be collected and maintained for study conduct; any 
unintentional identifiers will be removed from the data. A unique code will be generated for  
each aggregate and patient-level data variable and linked to a unique code representing the 
hospital unit and (for patient-level data) the patient. This identifier will be for purposes of the 
study only and will not include individually identifiable private information; it will be used to 
replace all individual identifiers in the data prior to analysis. De-identified patient-level data for 
which participants gave HIPAA authorization to share with the University of Wisconsin and 
deidentified aggregate data may be shared with the University of Wisconsin (the university 
affiliate) as specified in a valid Data Use Agreement. Otherwise, data will be saved to the 
Madison VA secure server behind the VA firewall. The shared data file will only be accessible 
via VA computers that are password protected and accessed only by research personnel. Logs 
of VCS gift cards given to participants containing participants’ study names and forms signed 
by participants (required in order to use the gift cards) will only be accessible by the minimum 
necessary study staff and staff from Fiscal/Budget offices at participating sites who may need to 
audit the logs. Computers will be maintained in locked offices with access only by research 
personnel. Interviews will be recorded on encrypted digital recorders or using Microsoft Teams 
and directly saved to the Madison VA secure server behind the VA firewall. When using 
Microsoft Teams access to the channel/meeting on which it is recorded will be restricted to 
study staff with permissions to access this data. The shared data file will only be accessible to 
study team members via VA computers that are password protected and automatically logged 
off when not in use. A unique number will be generated for each interview and this identifier will 

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be for purposes of the study only. Information linking identifier to audio recording or field notes 
will be maintained in a secure location; shared data file on the VA server behind the VA firewall 
accessed. The shared data file will only be accessible to study team members via VA 
computers that are password-protected and automatically logged off when not in use. Hard 
copies of field notes will be kept in locked file cabinets in locked offices accessed only by 
authorized research personnel. 
5.2.4.2 
Known Potential Benefits 
No direct benefits to patients and healthcare workers are anticipated, but patients may 
potentially benefit if the use of gloves by healthcare workers for all patient contact prevents the 
spread of organisms such as C. difficile within the hospital setting. Others may benefit in the 
future from what we learn as a result of the study, as our study will address critical gaps 
regarding effectiveness of universal gloving for CDI prevention. 
We hypothesize that the use of the universal gloving intervention will reduce C. difficile 
acquisition and infection within the units assigned to the intervention. 
If this study shows a decrease in the carriage of C. difficile, the community at large would 
benefit by eliminating a potential reservoir for disease transmission. Regardless of study 
results, important knowledge will be gained from the study guiding future research in the 
prevention of healthcare-associated CDI. 
5.2.4.3 
Assessment of Potential Risks and Benefits 
The risks to subjects in this study are minimal. In order to reduce risk and discomfort to 
subjects, we propose to collect stool samples when possible and then perirectal swabs f for 
measuring C. difficile. When perirectal swabs are collected, subjects can choose to have the 
RA/healthcare worker perform the perirectal swab or self -collect the perirectal swab. The 
intervention – universal gloving – is a non-invasive barrier precaution that has been a source 
of enthusiasm for VA healthcare facilities. As part of the study, we will also ask about 
stakeholders’ (patients and healthcare workers) experiences with universal gloving for all 
patient contacts versus standard of care. In addition, a sample of patients and healthcare 
workers will be asked to complete a survey regarding their perception of provider-patient 
contact using a 5-point Likert scale. This information will help us to understand if the 
intervention causes a burden or unintended consequences with study participants. 
The use of barrier contact precautions in both the intervention and control units will follow all 
standard of care procedures. It is expected of hospital accrediting standards and professional 
standards that equal; high quality care will be provided to all patients regardless of diagnosis. 
Patients on units that are in the intervention arm of the study where expanded barrier 
precautions (i.e., universal gloving) are used for all patient contacts will receive the same high- 
quality care as a patient in in the control arm of the study following standard of care procedures. 
Patients on units that are in the control arm of the study will have no change in their care. 
Educational materials used in the study will remind healthcare workers in the participating sites 
that patient care practices must conform to local facility standards regardless of whether 
expanded barrier precautions (i.e., universal gloving) are implemented for patient care. 
C. difficile is an important and increasing cause of morbidity and mortality in Veterans in VA 
hospitals and communities. As 1) there is the potential for both short- and long-term benefits in 
the reduction of C. difficile-associated morbidity and mortality based on the findings of this study 
and 2) the Veterans’ health, safety, and comfort has been maximized in our study design, we 
believe that the benefits of this study outweigh its minimal risks. 
5.3 Recruitment Methods 
INTERVENTION 
Ten inpatient units (two each from five participating VA facilities) will be included in the study, 
and the intervention will be conducted at the unit level. Multiple sites have previously expressed 

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interest in participating in an investigation of universal gloving as well as in healthcare- 

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associated infection prevention research in general. Communication describing the study and 
the study team’s/PI’s contact information will be distributed to facilities. Informational 
teleconferences will be offered for interested facilities to provide additional study requirements 
and eligibility criteria. Interested facilities will be sent a screening questionnaire to assess 
eligibility and facility support. 
 
This study is a cluster randomized trial: because all patients in a unit can contribute to 
transmission of C. difficile, the intervention needs to apply to all patients in the unit. As only VA 
facilities will be included, all patients in the unit will be aged 18 or greater. 
SPECIMEN COLLECTION 
Research staff will check with patient’s nurse or other healthcare team member (e.g., the 
nursing station) prior to approaching patients for specimen collection consent to determine if it 
is appropriate to approach a patient based on his/her health needs and other contextual 
factors, for example, whether there are any patients who should not be approached because 
they are in quarantine or not feeling well. We will work with unit staff to refine the process for 
identifying patients who may be approached as needed based on unit staff’s preferences; for 
example, members of the healthcare team may wish to make first contact with a patient by 
asking if they may introduce the RA to discuss a research opportunity or by distributing flyers 
describing the study prior to the RA visit to the unit. Research staff will approach those patients 
deemed appropriate on the participating units on the first study day and then subsequently 
newly admitted patients to ask if they are willing to speak about a voluntary research 
opportunity. If so, the RA will review study details and ascertain the patient’s interest in 
providing a stool or swab specimen. The RA will assess whether it is a good time to approach 
the patient (e.g., by checking with the patient’s nurse or other healthcare team member) prior 
to approaching the patient. The healthcare team members will not screen for eligibility or 
directly recruit patients to participate in specimen collection. Rather, the healthcare team 
member’s role is to facilitate patient care by being an advocate for the patient. Admitted 
patients will be identified from VA administrative records (e.g., from the CDW) and the 
admission and discharge tracking system used by the participating unit (e.g., the gains and 
loss report). 
 
Patient participants will be offered a $15 Veterans Canteen Service (VCS) gift card (Patriot Bucks) 
in exchange for their participation in the study at local sites where and when VCS gift cards are 
made available to the local study team. The gift card will be given to the patient by the RA after the 
patient provides their first specimen, regardless of whether the patient provides a second 
specimen prior to discharge (i.e., even if the subject later withdraws from the study). Versions of 
recruitment flyers referencing the gift cards will be used whenever and wherever VCS gift cards 
are available. 
 
INTERVIEWS 
We will recruit individual healthcare workers and patients for interviews about their experience 
with the intervention. 
 
Healthcare Workers 
We will conduct focus groups/interviews with up to 12 healthcare workers at each participating 
unit assigned to the intervention, for a total of up to 60 healthcare workers involved in focus 
groups. Prior to beginning the focus groups/interviews, which may take place throughout the 
intervention period, the Local Site Investigator and Research Assistant will discuss recruitment 
options with unit leadership. Recruitment strategies may include presentations at staff meetings 
(using verbal script) or email to unit staff. The LSI or local RA will lead these recruitment 
strategies, for example by presenting at staff meetings or sending emails. 
Recruitment for these focus groups may also include emails to unit staff. We will discuss with 
unit leadership/supervisors if email is appropriate to use for their staff and, if so, how to access 
these email addresses. We will discuss with site staff, including unit leadership/supervisors and 

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local research staff, who should send the email – it will come from either the LSI, the local RA, 
or a member of the central research team. The email will include contact information so 
recipients can reply to the appropriate research team member to agree to participate, decline 
participation, or ask questions. Staff receiving study information sheets will be able to contact 
the study team to participate or select opt-in option on the study information sheet whereby the 
study team will contact them. Staff who select the opt-out option of the study information sheet 
will not be contacted and removed from the potential list of participants. If we do not hear a 
response (either agreement/declination to participate or request to not be contacted again), we 
will follow-up a maximum of two additional times via email and/or phone. 
During the recruitment process, regardless of outreach method, each potential participant will 
receive the interview information sheet. The healthcare worker will have time to review the 
sheet, and research staff will answer any questions they have before asking if they would like 
to participate. Healthcare workers who agree to participate in interviews will be given a brief, 
voluntary, anonymous demographics survey by the local RA (e.g., with the interview 
information sheet) to complete before or after the interview. Healthcare workers may 
participate in interviews even if they decline to complete the demographics survey. 
 
Healthcare worker interview guides will be submitted to the appropriate unions for review prior 
to launching procedures. Interviews will take place during non-work time (e.g. lunch hour) or 
during supervisor-approved work time (e.g. during regularly scheduled staff meetings where 
patients have coverage and supervisors can leave the area). Supervisors will be notified prior to 
beginning any interview recruitment procedures. 
 
Patients 
We will interview 10 patients at each participating unit assigned to the intervention for a total of 
50 patient interviews. During the intervention period, the site Research Assistant will work with 
unit staff to identify and approach patients. The RA will discuss with unit staff to determine if it 
is appropriate to approach a patient based on his/her health needs and other contextual 
factors; for example, patients will not be approached who are receiving end-of- life care, are 
cognitively impaired, or are unable to understand English. Patients who are under contact 
precaution isolation above and beyond the intervention (for example, use of gowns and gloves 
for all patient contact) will not be approached for interviews. We will work with unit staff to 
refine the process for identifying patients who may be approached as needed based on unit 
staff’s preferences; for example, members of the healthcare team may wish to make first 
contact with a patient –by asking if they may introduce the RA to discuss a research 
opportunity or by distributing flyers describing the interviews prior to the RA visit to the unit. 
The healthcare team member will not screen for eligibility or directly recruit patients to 
participate in interviews. Rather, the healthcare team member’s role is to facilitate patient care 
by being an advocate for the patient. 
 
The RA will check with the patient’s nurse or other healthcare team member before 
approaching the patient to ask him/her to participate and will not approach any patient without 
the nurse’s or other healthcare team member’s agreement that it is a good time to do so. The 
RA will not approach patients who have indicated they do not want to be contacted, receiving 
end-of-life care, cognitively impaired, non- English speakers, in contact isolation precautions or 
when he/she is undergoing any medical procedures. The RA will ask the patient in his/her room 
if he/she is willing to speak about a voluntary research opportunity. If so, the RA will meet face- 
to- face with the patient to assess eligibility and to provide basic information regarding the study 
and the voluntary nature of participation. A liberal amount of time will be allotted for discussion 
of the study and the patient’s role in the study, and to answer any questions posed by the 
patient. The written information sheet will also be provided to the patient. The RA will offer the 
potential subject time for private contemplation and review of the documents provided or time to 
discuss the study with important support persons not currently with the patient. If the patient 
decides to participate, he/she can tell the RA in person or via the provided contact information 
in order to set up an interview. The RA will ask for the patient’s phone number so that the 

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patients can be contacted regarding the interviews. In addition, the RA will ask the patient if the 
RA may return to the patient at a later time to check in about their decision. The RA may return 
to the patient one additional time to follow-up, and only with the patient’s approval to do so 
based on the recruitment script. Patients who agree to participate in interviews will be given a 
brief, voluntary, anonymous demographics survey by the local RA (e.g., with the interview 
information sheet) to complete before or after the interview. Patients may participate in 
interviews even if they decline to complete the demographics survey. 
SURVEYS 
Patients 
We will work with unit staff to refine the process for identifying patients who may be 
approached as needed based on unit staff’s preferences; for example, the healthcare team 
member may wish to make first contact with a patient –by asking if they may introduce the RA 
to discuss a research opportunity or by distributing flyers describing the survey prior to the RA 
visit to the unit. The healthcare team member will not directly recruit patients to participate in 
the surveys. The RA will check with the patient’s nurse before approaching the patient to ask 
him/her to participate and will not approach any patient without the nurse’s agreement that it is 
a good time to do so. We will recruit patients to complete a Patient-Provider Contact Survey to 
understand perceptions of whether contact with patients is impacted due to the intervention. 
No PII or PHI will be included on these surveys. We will aim to obtain 10 patient surveys per 
site. 
We will work with unit staff to determine how to share the survey with patients; options may 
include leaving the survey on bedside table, including survey in admission/discharge 
paperwork, and/or having research staff explain the survey and ask patient if they are willing to 
participate. A pen/pencil will be provided to patients who wish to complete the survey. We will 
collect completed surveys through a discreet, anonymous receptacle and/or the RA picking up 
surveys from patients who have agreed to complete the survey. 
Environmental Services Workers 
We will also recruit environmental services workers to complete a survey of their experiences 
with the intervention (e.g. to determine if the increased gloving impacts their workload). No PII 
or PHI will be included on these surveys. We will aim to obtain 1 survey per site. 
 
We will discuss with supervisors prior to beginning any recruitment or survey procedures in 
order to determine the appropriate recruitment strategies for the local team and its workflow. 
Recruitment options include leaving an introductory flyer as well as the information sheet and 
survey itself in staff mailboxes. In addition, we may present the project and information sheet at 
regularly scheduled staff meetings where the supervisor is not present. We will provide time to 
answer questions as well as information for how to complete and return surveys. A discreet, 
anonymous receptacle will be placed for completed surveys. The survey completion should take 
no more than 5 minutes and thus should not interfere with work duties. 
5.4 Informed Consent Procedures 
Verbal Informed consent and signed HIPAA authorization will be obtained for stool sample 
collection from the participant. 
We are requesting a waiver of informed consent for the intervention (use of universal 
gloving) and access to unit records (patient admission and discharge; gains and loss 
report, VA administrative records on unit admissions and discharges) to track 
compliance with study procedures and measure unit-level clinical outcomes and 
observe healthcare worker compliance with gloving procedures. We will work with each 
facility to determine how they normally track admission and discharge. We anticipate 
that most, if not all, sites will utilize the standard gain and loss report or admission, 
discharge, transfer (ADT) report available on VISTA; thus, we plan to use this report to 

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track admission and discharge. To track unit-level clinical outcomes, we will either ask 
units to provide this information to us using standard reporting parameters for each site, 
or we will access this information via CPRS, VISTA, and/or the VA administrative 
records (e.g., the CDW). 
We are requesting a waiver of documentation of informed consent for patient specimen 
collection and healthcare worker/ patient interviews, focus groups, and surveys. 
We are requesting waivers of consent because: 
It is not possible to carry out the study using written individual informed consent. In this study, 
we are performing a cluster randomized trial. Cluster randomized trials such as these most 
often are granted waived consent due to the inability to carry out the research without waiver 
of consent. As is the case for many infection control or behavioral interventions, this 
intervention cannot be studied using a traditional patient-level randomization because: a) the 
intervention is difficult if not nearly impossible to randomize to individual patients in the unit 
and not other patients; b) there are group-level variables in patient units (patient-specific 
variables and healthcare worker-specific variables) that make the CRT the most valid study 
design; and c) bacteria transmission does not occur on the individual level but on a group 
level within a patient unit. An example of a group level variable is colonization pressure. 
Colonization pressure, defined as the percent of patients in a given patient unit with an 
infectious agent such as an antibiotic-resistant organism (MRSA), affects the probability of 
other patients acquiring the bacteria and developing an infection (primary and secondary 
outcomes of the study). Since wearing gloves and gowns to care for a particular patient (e.g., 
patient A) would protect that patient from acquiring an infection, but would also prevent other 
patients (e.g., patient B, patient C, patient D) in the same unit from acquiring bacteria from 
patient A. Another reason is that if the study was randomized to individual patients, it is likely 
that healthcare workers would be influenced by the intervention of wearing gloves and gowns 
and potentially being more adherent to other infection control practices. A patient-level 
randomized trial is inadequate to study interventions that reduce transmission of infections. 
CRT is the preferred design in many infectious disease and infection control studies when the 
investigator is worried about contamination of intervention to control patients. 
(1) The research involves no more than minimal risk to the participant. Use of barrier contact 
precautions (gloving plus gowning) is currently the standard of care for patients with certain 
communicable diseases including antibiotic-resistant organisms (e.g., MRSA), so the 
expansion of universal gloving for care of all patients (intervention) does not present additional 
risk to healthcare workers or patients. 
 
 
(2) The waiver will not adversely affect rights and welfare of participants. Use of barrier 
precautions are currently the standard of care for patients with certain communicable diseases 
including antibiotic-resistant organisms (e.g., MRSA). It is expected of hospital accrediting 
standards and professional standards that equal; high quality care will be provided to all 
patients regardless of diagnosis. Patients on units that are in the intervention arm of the study 
where barrier precautions are used for all patient contacts will receive the same high-quality 
care as a patient in which barrier precautions are either being used for other purposes or not 
being used at all. Patients on units that are in the control arm of the study will have no change 
in their care. Educational materials used in the study will remind healthcare workers in the 
participating sites that patient care practices must conform to local facility standards regardless 
of whether barrier precautions are implemented for patient care. 
(3) Whenever appropriate, additional pertinent information will be provided to participants after 
participation. In the event that patients or healthcare workers request study information, each 
site will have readily available copies of the study information sheet which describes the 
purpose of the trial, the procedures involved in the trial, and who to contact for further 
information. No individual patient information will be provided. 

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5.4.1 Consent Procedures and Documentation 
 
SPECIMEN COLLECTION (STOOL SAMPLE) 
Research staff will provide study details and obtain verbal informed consent and signed HIPAA 
authorization from all subjects prior to swab/stool specimen and data collection. The study team 
will provide time to answer questions and clarify consent procedures. Interested subjects will be 
provided with an information sheet. A version of the information sheet detailing subject payment 
details will be used by local sites when VCS gift cards are available to them. An information sheet 
without reference to subject payments will be used whenever and wherever VCS gift cards are 
available for them to use. Where required by local policy, consent will be documented in the 
electronic medical record. 
If the subject is unable to consent (incompetent, impaired decision-making capacity), the 
subject’s legally authorized representative will be asked to provide verbal informed consent, 
and the subject’s Personal Representative will be asked to provide written HIPAA 
authorization. No subjects who are unable to consent will be enrolled in the study unless 
verbal consent has been obtained from a legally authorized representative and written HIPAA 
authorization has been obtained from a Personal Representative. Local research personnel 
will follow all applicable laws and regulations. VHA Directive 1605.01 defines a personal 
representative as a person who, under applicable law, has authority to act on behalf of the 
individual to include privacy- related matters. The authority may include a power of attorney, 
legal guardianship of the individual, appointment as executor of the estate of a deceased 
individual, or a Federal, State, local or tribal law that establishes such authority (e.g., parent of 
a minor).” Competency of the subject will be determined by previous clinical assessment as 
documented in the medical record. If competency has not been documented in prior notes and 
we determine that the subject cannot consent, then discussion with the treating team 
regarding capacity to consent will ensue. In case of patients deemed incompetent or with 
impaired decision-making capacity, the legal representative would be contacted first and then 
a relative asked to consent for them. The legally authorized representative for the subject will 
be documented in the medical record (progress note or copy of legally recognized document). 
If the subject is later deemed to be competent, they will be re-consented as soon as possible. 
The plan for re-consenting subjects with fluctuating decision-making capacity or those who 
regain consent capacity is to review the study and consent materials and provide information 
on their previous participation and surrogate consent. Subject dissent would overrule surrogate 
consent. The subject or their representative (legally authorized representative or Personal 
Representative) will be first approached by the clinical care team to assess their interest in the 
trial. The following persons will be contacted in the following order of priority: a. health care 
agent (individual named as a power of attorney), b. legal guardian or c. next of kin in this order 
(spouse, child, parent, sibling, grandparent or grandchild) or d. close friend. The subject’s 
medical record will be examined to determine whether a Personal Representative is 
documented. If a Personal Representative is not identified from the medical record, research 
personnel will ask the legally authorized representative whether the subject has a Personal 
Representative, and if so, who the Personal Representative is. The Personal Representative 
will be provided with the study information sheet and HIPAA authorization form. If the subject’s 
legally authorized representative is also a subject’s Personal Representative, they will be 
asked to provide both verbal consent and written HIPAA authorization. If no Personal 
Representative is identified, or the Personal Representative does not provide written HIPAA 
authorization, the subject will not be enrolled in the study unless they later gain capacity to 

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provide consent and HIPAA authorization for themselves, even if a separate legally authorized 
representative has provided verbal consent for the subject’s participation. 
Documentation by a qualified practitioner in the individual’s medical record in a signed and 
dated progress note that the individual lacks capacity to make the decision to participate in the 
proposed study. NOTE: the qualified practitioner may be a member of the research team OR 
the individual has been ruled incompetent by a court of  law. Disclosures required by the VA to 
be made to the subject by the investigator (the informed consent process) must be made to the 
subject’s surrogate(s) (legally authorized representative and Personal Representative). 
Discussion of the major aspects of the study with the surrogate(s) may take place either in 
person or over the phone. The surrogate(s) will be informed that their decision should be 
based upon that which the surrogate believes is, or would be, desired by the subject. If a 
subject’s wishes cannot be determined, surrogate decisions should be based upon that which 
the surrogate believes to be in the subject’s best interest. If feasible, the practitioner will 
explain the proposed research to the prospective research subject even when the surrogate 
gives consent. Under no circumstances will the subject be forced or coerced to participate in a 
research study. Local site study personnel will be required to complete VA human subject 
protections training requirements prior to the start of the intervention phase of the study. In 
addition, local research staff will attend a virtual training session on how to obtain and 
document informed consent that will be conducted by the coordinating site (Madison VA) 
research staff. 
INTERVENTION (UNIVERSAL GLOVING) 
As this is a cluster randomized trial, all healthcare workers/patients within a unit will need to 
participate in the intervention/comparator (as assigned) and data collection in order to ensure 
meaningful data. 
 
If the patient lacks decision-making capacity, the research staff will provide information to the 
caregiver(s)/Legally Authorized Representative (LAR). The information will be given to 
caregiver(s)/LAR when the subject is unconscious or clearly lacking capacity. When a 
caregiver/ LAR is not present in the unit, the study information sheet will be mailed. The mailing 
will be determined in the following order of priority: a. health care agent (individual named as a 
power of attorney), b. legal guardian or c. next of kin in this order (spouse, child, parent, sibling, 
grandparent or grandchild) or d. close friend. This information will be determined by unit staff 
using established procedures. 
SURVEYS/INTERVIEWS 
 
Patients and healthcare workers who are participating in surveys and/or interviews/focus 
groups will be informed that participation is voluntary and that they may withdraw from 
participation at any time, without prejudice. The rights and welfare of the participants will be 
protected by emphasizing to them that the quality of their medical care will not be adversely 
affected if they decline to participate in this study. They will receive information sheets 
describing the purpose of the study, the procedures involved, and who to contact for further 
information. 
5.5 Inclusion/Exclusion Criteria 
VA inpatient units meeting the following criteria are eligible to participate in the study: 
1. Ability to identify one of the following inpatient units as defined by CDC National 
Healthcare Safety Network30 by reviewing prior 12-month patient mix data (at least 80% 
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a. Adult Acute Medical Ward: Hospital area for the evaluation and treatment 
of patients with medical conditions or disorders. 
b. Adult Acute Medical/Surgical Ward: Hospital area for the evaluation of 
patients with medical and/or surgical conditions. 
c. Adult Acute Surgical Ward: Hospital area for evaluation and treatment of 
patients who have undergone a surgical procedure. 
2. Ability to store collected admission and discharge stool samples from patients prior to 
batch mailing 
3. Ability to collect and upload data (HAIs, mortality, length of stay, hand hygiene and 
barrier precaution compliance; glove use and glove plus gown use for CP) required for 
analysis 
4. Local R&D Committee approval 
5. Letter of support from the Hospital Director or Chief of Staff. 
Intensive care units, long term care units, and mixed-acuity will be excluded. To participate 
in interviews or focus groups, the individual must be: 
1. 18 years of age or older 
2. A patient admitted to the participating unit OR a healthcare worker who has regular work 
duties on the participating unit. 
To participate in specimen and clinical data collection, the individual must be: 
1. 18 years of age or older 
2. A patient admitted to the participating unit. 
5.6 Study Evaluations 
Patient-level data 
C. difficile Acquisition: In both the intervention and control groups, we will obtain one swab or 
stool sample upon admission and one swab or stool sample upon discharge to test for the 
presence of C. difficile. This outcome data will be collected on an individual patient level, but de- 
identified prior to reporting. These test results will not be available to healthcare workers or 
patients at participating sites. Acquisition will be defined as a patient who has an initial test (via 
stool or perirectal swab) upon unit admission that is negative for C. difficile and a subsequent 
discharge test within the same unit that is positive for C. difficile. 
Specimen collection 
Research staff and/or clinical staff in both the intervention and control arms of the study will 
implement a standard protocol for obtaining stool or perirectal swab (depending on patient 
preference) samples for C. difficile test using standardized clinical methodology. Samples will be 
collected within 72 hours of patient admission and within 72 hours of anticipated discharge of all 
patients in participating units. C. difficile testing via stool sample will be obtained by using a toilet 
hat to collect stool and storing a sample of the stool in a sterile contained. C. difficile testing via 
perirectal swab sample will be obtained by swabbing the perianal area (a swab from the anal 
verge, without rectal insertion) in a circular motion, ideally until visible stool is noted on swab. 
The swab samples will be obtained in a private room or the privacy curtain will be drawn in 
semi-private rooms to protect patient privacy. The discharge sample may be collected within 
72 hours prior to estimated discharge date or, if the patient is transferred to another unit within 
the participating facility, within 48 hours after discharge from the unit. Samples collected by 
research staff will be labeled with unique identifier. Samples collected by clinical staff or 
patient self-collected samples will be labeled in the unit by clinical staff with standard clinical 
pre-printed patient labels and collected on site by Research Assistants who will relabel 
specimens with unique identifiers, These collected samples will be refrigerated according to 
procedures defined by laboratory staff to ensure sample quality and then ship in batches to the 
Madison VA research laboratory. 
The specimens will be shipped to a central microbiological research laboratory at the Wm. S. 

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Middleton Memorial VA Hospital in accordance with mandated U.S. regulations governing the 
shipment of Diagnostic Samples, Dangerous Goods and dry ice.31 No patient identifiers will be 
received by the central laboratory. Microbiological work-up for C. difficile will follow Clinical and 
Laboratory Standards Institute procedures32 and the use of a central microbiological laboratory 
to process these specimens will assure standardized microbiological (or molecular) methods 
and processing of the samples. Specimens will be tested for C. difficile, and C. difficile isolates 
will be tested for in vitro cytotoxin production using previously described procedures.29 
Shipments will be tracked using a shared database stored on the VA server. 
Participants (patients and staff) will not be informed of the results of the cultures. The 
cultures are measuring C. difficile colonization, not infection. There is currently no treatment 
for C. difficile colonization, and many patients who are colonized with C. difficile are and 
remain asymptomatic. Thus, informing participants of a positive C. difficile culture could result 
in undue stress and unnecessary treatments to the patient given the possibility that the 
colonization will remain asymptomatic. In addition, it remains unknown whether altering 
behaviors of healthcare workers could impact the spread of C. difficile from asymptomatically 
colonized patients and thus there is no standard for how to care for a patient that is found to 
be asymptomatically colonized. So, it is not currently useful to inform healthcare workers 
simply of positive cultures. However, patients that develop symptoms of C. difficile infection, 
such as diarrhea, will be cultured and treated according to the standard of care in all 
intervention and control units. Specimen results will be stored on a database on the VA 
server, unless otherwise specified in a valid DUA. 
Demographics: In both the intervention and control groups, for patients who consented to 
clinical data collection, we will obtain data on demographic characteristics (age, gender, race, 
weight, height) from VA administrative records (e.g., Corporate Data Warehouse [CDW] files). 
These data will be linked to patient specimen results (e.g., C. difficile colonization) and stored 
on a shared database on the VA server, unless otherwise specified in a valid DUA. 
Past medical history/other hospitalization characteristics: In both the intervention and 
control groups, for patients who consented to clinical data collection, we will obtain data on the 
following characteristics from VA administrative records (e.g., using healthcare utilization 
dates, prescriptions, and diagnostic/treatment codes from CDW files): hospitalization 
characteristics (dates of admission to and discharge from the healthcare facility and 
participating unit, disposition [to acute care, home, home services, or skilled nursing 
facility/nursing home/long-term care facility], and source [i.e., where the patient was admitted 
from], treatments and healthcare utilization within the 90 days prior to admission and CDI 
occurring during their admission (antibiotic use, proton-pump inhibitor use, visits to healthcare 
facilities [emergency department, infusion services such as chemotherapy, hemodialysis]), 
CDI-related surgical intervention prior to admission, and comorbidities (acute renal failure, 
asthma, cancer, congestive heart failure, chronic obstructive pulmonary disease, 
cardiovascular disease, dementia, diabetes, inflammatory bowel disease, liver disease, 
paralysis, peripheral vascular disease, renal disease, rheumatic disease, peptic ulcer disease). 
These data will be linked to patient specimen results and stored on a shared database on the 
VA server, unless otherwise specified in a valid DUA. 
C. difficile infection: In both the intervention and control groups, we will determine the 
development of C. difficile infection during admission among patients who consented to clinical 
data collection by obtaining data from VA administrative records (e.g., using diagnostic codes 
from CDW files). These data will be linked to patient specimen results and stored on a shared 
database on the VA server, unless otherwise specified in a valid DUA. 
Other Healthcare-Associated Infections: The incidence of other HAIs including: 1) catheter- 
associated bloodstream infection (CLABSI), 2) catheter-associated urinary tract infection 
(CAUTI), and 3) MRSA HAIs during admission among patients who consented to clinical data 
collection will be obtained from VA administrative records (e.g., using diagnostic codes from 
CDW files) for both the intervention and control groups. These data will be linked to patient 
specimen results and stored on a shared database on the VA server, unless otherwise 

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specified in a valid DUA. 
Mortality: In both the intervention and control groups, mortality among patients who consented 
to clinical data collection will be obtained from VA administrative records (e.g., using date of 
death from the CDW files). These data will be linked to patient specimen results and stored on 
a shared database on the VA server, unless otherwise specified in a valid DUA. 
Other clinical outcomes: In both the intervention and control groups, for patients who 
consented to clinical data collection, whether the patient had toxic megacolon or a colectomy 
will be obtained from VA administrative records (e.g. using diagnostic/treatment codes from 
CDW files). These data will be linked to patient specimen results and stored on a shared 
database on the VA server, unless otherwise specified in a valid DUA. 
Unit-level data 
C. difficile Infection: The development of C. difficile infection will be determined by 
standard clinical care which is the presence of clinical symptoms and positive laboratory 
results. In both the intervention and control groups, hospital-onset (HO)-CDI will be 
collected monthly as a unit aggregate rate. In this case, hospital refers to the study unit. 
Research personnel will collect these data from site personnel (i.e., infection control) at 
participating sites which are collected as usual standard of care. The CDC definition of 
HO-CDI, used by the VA,33 is defined as: 1) LabID Event specimen collected >3 days 
after admission to the facility (i.e., on or after day 4) and 2) CDI-positive laboratory 
assay: A positive laboratory test result for C. difficile toxin A and/or B, (includes 
molecular assays [PCR] and/or toxin assays) tested on an unformed stool specimen 
(must conform to the container) OR A toxin-producing C. difficile organism detected by 
culture or other laboratory means performed on an unformed stool sample (must 
conform to the container). The data will be uploaded to a shared database on the VA 
server, unless otherwise specified in a valid DUA. 
Other Healthcare-Associated Infections: The incidence of other HAIs including: 1) catheter- 
associated bloodstream infection (CLABSI), 2) catheter-associated urinary tract infection 
(CAUTI), and 3) MRSA HAIs will be measured. HAI data will be collected monthly for both the 
intervention and control groups using standard CDC/VA definitions. Research staff will collect 
monthly aggregate data from site personnel (i.e., infection control) at participating sites which 
are collected as standard of care reporting to VA IPEC (inpatient evaluation center) and/or 
from VA administrative records. The rate will be calculated by the number of CAUTI or 
CLABSI per number of device days (i.e., Foley catheters or central lines) 
 1,000 and the 
number of MRSA infections per number of patient days x 1000. The data will be uploaded to 
a shared database on the VA server, unless otherwise specified in a valid DUA. 
Mortality: In both the intervention and control groups, research staff will collect monthly 
aggregate 30-day mortality ratio data from site personnel (i.e., nurse manager) at participating 
sites which are collected as standard of care reporting to VA IPEC and/or from VA 
administrative records. The data will be uploaded to a shared database on the VA server, 
unless otherwise specified in a valid DUA. 
Length of Stay: In both the intervention and control groups, research staff will collect monthly 
aggregate length of stay (i.e., the number of days spent in the participating unit based on unit 
admission and unit discharge) data from site personnel (i.e., nurse manager) at participating 
sites which are collected as standard of care reporting to VA IPEC and/or from VA 
administrative records. The data will be uploaded to a shared database on the VA server, 
unless otherwise specified in a valid DUA. 
Intervention Fidelity Data: 
Hand Hygiene Compliance: In both the intervention and control groups, hand hygiene 
compliance will be measured on a random sample of healthcare workers caring for patients. 
Research staff will perform monthly observations that will be recorded on a standard 
observation tool; participating site research staff will be trained by study coordinating site 
research staff. WHO manual for observers recommends observing a minimum of 200 hand 

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hygiene opportunities during each measurement period in each unit.34 We estimate the number 
of hand hygiene opportunities as 10 opportunities per patient per hour. 35 The average unit will 
have 20 patients, therefore each month research personnel will observe hand hygiene 
opportunities for one hour to generate the minimum observation of 200 hand hygiene 
opportunities per unit per month. The data will be uploaded to a shared database on the VA 
server, unless otherwise specified in a valid DUA. 
 
Contact Precaution Compliance: In both the intervention and control groups, barrier 
precaution compliance (i.e., healthcare worker glove plus gown use during care of patients in 
CP isolation) will be measured on a random sample healthcare worker contacts during care of 
patients in CP isolation. Research staff will perform monthly observations that will be recorded 
on a standard observation tool; participating site research staff will be trained by study 
coordinating site research staff. We estimate the average number of patient contacts by 
healthcare workers using barrier precautions to be 60 contacts per day.36 The average unit will 
have 2-6 patients (10-30%) in CP isolation; each month research personnel will observe for 
one hour to generate 10% sample of 12 healthcare worker contacts using minimum estimate of 
patients in isolation. The data will be uploaded to a shared database on the VA server, unless 
otherwise specified in a valid DUA. 
 
Universal Gloving Compliance: In the intervention group, universal gloving compliance will 
be measured on a random sample of healthcare workers caring for patients. Research staff 
will perform monthly observations that will be recorded on a standard observation tool; 
participating site research staff will be trained by study coordinating site research staff. We 
will use hand hygiene opportunity estimates34,35 as surrogate for patient contact opportunities 
requiring gloving. The average unit will have 20 patients, therefore each month research 
personnel will observe gloving opportunities for one hour to generate the minimum 
observation of 200 patient contact opportunities per unit per month in the intervention unit 
only. The data will be uploaded to a shared database on the VA server, unless otherwise 
specified in a valid DUA. 
Isolation Days of Care: Contact precautions can be used for reasons other than CDI such 
as antibiotic resistant organisms (e.g., MRSA). If a large proportion of barrier precautions are 
being used in the control group for these types of patients, it could confound the study 
endpoints. To account for this, we will collect and estimate isolation days of care. In both the 
intervention and control groups, research staff will collect monthly aggregate data on isolation 
patients from site personnel (i.e., infection control) at participating sites which are collected 
as standard of care reporting. We will estimate the isolation days of care by multiplying the 
number of patients on CP isolation by the average length of stay for the participating unit. 
The data will be uploaded to a shared database on the VA server, unless otherwise specified 
in a valid DUA. 
Interviews 
Healthcare Worker Experience: The study team plans to explore healthcare workers 
experience using barrier precautions for all patient contacts vs standard of care using 
qualitative methodology. Questions will address five main areas: 1) understanding of the 
rationale for universal gloving to reduce and prevent CDI; 2) barriers and facilitators to 
implementing universal gloving; 3) perceptions around how the intervention influenced 
healthcare workers’ care of and interactions with patients and other aspects of their jobs; 4) 
how the healthcare workers integrated universal glove donning into their regular workflow; and 
5) any other issues or areas of concern around the intervention. 
Qualitative focus groups of healthcare workers (physicians, registered nurses, and health 
technicians who have regular and direct patient contact) will be conducted at each 
participating unit assigned to the intervention throughout the study period. Each focus group 
will include up to 12 individuals. They will last about 45 minutes with moderators following a 
structured interview guide, adding additional probing questions to facilitate discussion. One 

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moderator (either the trained LSI or local RA, or a member of the Madison-based study team) 
will facilitate each group discussion while another trained professional will record field notes 
during the group to track the flow of conversation and document nonverbal behaviors. 
Interviews may take place either in-person, led by trained local research staff, or virtually 
(telephone or webinar), led by central research staff. The central research team has previous 
experience with virtual focus groups. Group discussions will be audio recorded (unless 
participants decline to be recorded, in which case field notes will be taken instead), and tapes 
transcribed. Qualitative analysis will be used to identify codes, categories, and themes. 
Participants will be asked to complete a brief, voluntary, anonymous demographics survey that 
the local RA will give to the participant to complete before or after the interview (e.g., along 
with the interview information sheet or form 10-2303). The RA will collect the surveys from the 
participants once the surveys are complete. Demographic characteristics will not be linked to 
individual participants, and only aggregate demographic information will be obtained during 
analysis and shared during manuscript preparation. 
Patient Experience: The study team plans to explore patient experience with healthcare 
workers use of universal gloving for all patient contacts vs standard of care using qualitative 
methodology. Questions will address three main areas: 1) patients’ perceptions of the staff’s 
practice of universal glove donning, including positive and negative perceptions; 2) any changes 
in care or interactions that patients perceive were related to universal glove donning; and 3) 
patients’ understanding of the potential benefits of the intervention. 
Individual interviews with 10 patients will be conducted at each participating unit assigned to the 
intervention during the intervention period. Patient interviews will be conducted either by trained 
Madison VA staff via Microsoft Teams and/or telephone or by the trained local RA in a private 
setting. For patients in private rooms, the door will be closed. For patients in semi-private 
rooms, they will be asked if drawing the privacy curtain is adequate to meet their privacy needs, 
and for those granting permission the privacy curtain will be drawn. Each session will be 15-30 
minutes with moderators following an interview guide, adding additional probing questions to 
facilitate discussion. Interviews will be audio recorded (unless participants decline to be 
recorded, in which case field notes will be taken instead), and tapes transcribed. Qualitative 
analysis will be used to identify codes, categories, and themes. Participants will be asked to 
complete a brief, voluntary, anonymous demographics survey before or after the interview. The 
RA will collect the surveys from the participants once the surveys are complete. Demographic 
characteristics will not be linked to individual participants, and only aggregate demographic 
information will be obtained during analysis and shared during manuscript preparation. 
Cost Analysis 
Cost: We will conduct a cost-identification analysis to assess cost of providing the intervention. 
To estimate costs of the intervention of universal gloving, we will obtain cost data direct 
observation, estimates and consultation with the study facility. To estimate the cost of the 
intervention, we will calculate the cost of implementing universal gloving and the usual care 
barrier approach. The cost of glove supply costs will be obtained from the research team and 
facility. We will also estimate the supply costs associated with the usual care gloving. We will 
estimate supply costs by collecting glove use data. We will obtain a monthly list of supplies (i.e., 
gloves) issued to each participating unit in both groups from their distribution departments. To 
estimate the return on investment of using universal gloving, we will also estimate the potential 
savings that result from a decrease in C. difficile infections and colonization. We will compare 
estimated HAI costs obtained from the literature before and after the intervention. We will 
estimate HAI costs based on published reports.37 
Survey 
Provider-Patient Contact: Surveys of patients will be used to assess perception of provider- 
patient contact and patient satisfaction with this contact. Survey results will be compared 
between the control or intervention group to determine if the intervention may be impacting 
patient satisfaction with their care. Surveys will be conducted during the patient’s stay in the unit 
and may be returned to any member of their care team or left at the nurse’s station upon 

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discharge. The local research assistant will collect all surveys for analysis. 
Environmental Services Experience: Healthcare workers in environmental services will be 
surveyed to determine if the additional use of gloves in the unit may be impacting 
workflow/workload (for example, by increasing the frequency of trash disposal required on the 
unit). Surveys may be returned to a secure location (e.g. a drop box) and the local research 
assistant will collect all surveys from this location for analysis. 
5.7 Safety Monitoring 
This study poses minimal risk to participants. To ensure the safety of healthcare workers and 
patients in participating units we will use regularly collected VA quality and safety metrics. 
Metrics that are regularly collected by VA that will be monitored here may include information 
on falls, hand hygiene compliance, contact precaution/personal protective equipment use 
compliance, and patient satisfaction (e.g. SHEP scores). Hand hygiene and contact precaution/ 
personal protective equipment use compliance data from observations conducted as part of our 
research will be complemented with standard data collected by infection control to monitor for 
changes in adherence to infection control practices. 
We will work with the LSI and RA at each site to develop a site-specific plan for transmitting 
these metrics, i.e., whether the Madison study team will download these aggregate data from 
the Corporate Data Warehouse or whether the local study team will upload these data to the 
Madison study team using VA-secure methods behind the VA firewall. The Provider-Patient 
Contact survey will also be used to monitor patient responses to the intervention and ensure 
that the universal gloving practices are not causing a negative impact on patient experience. 
Given the minimal risks posed by this study, we do not anticipate that any safety conditions will 
trigger suspension of the study. If we find significant negative impacts, we will notify the site LSI 
to communicate issues with unit leadership and develop a response plan. For example, if hand 
hygiene compliance data show a significant negative impact upon introducing the intervention, 
we will work with the LSI and unit leadership to educate unit staff on the importance and 
workflow of hand hygiene in combination with gloving practices. 
5.8 Data Analysis 
5.7.1 Sample Size Determination 
Initial power calculation determined that 10 patient units are necessary to detect a 36% relative 
reduction (6.2%) in acquisition of C. difficile in the intervention vs. no reduction in the control 
group based on a presumed rate of 9.7 acquisitions per 1,000 patient days; recent literature 
report an average C difficile acquisition rate of 9.7 per 1,000 patient-days 38 and expected 
reduction of C. difficile acquisition of 36%. 39 Each arm of the study will require 9,879 patient 
days of care. On average, it is estimated that each patient unit will have a 25-bed capacity with 
an estimated 100 admissions per month and 5-day length of stay. We will plan to enroll 10 units, 
5 for each arm. These power calculations will be revised based on actual baseline-period data. 
The statistical power calculation was conducted using G*Power.40 We have incorporated an 
intracluster coefficient of 0.40 for this study. 

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5.7.2 Statistical Analyses 
Analyses will be conducted by the lead biostatistician in collaboration with resources from the 
Coordinating Site Committee (see above). 
Demographics: All unit level and patient level categorical demographic information will be 
summarized on table 1 as proportions and frequencies. We will output all continuous data using 
mean plus standard deviation or median plus range. 
C. difficile acquisition Rate: Acquisition rates will be obtained from each unit and comparisons 
for differences between control and intervention units using a chi-squared test. We will 
conduct a crude and adjusted linear and logistic regression model to determine predictors of 
C.diff acquisition in patients. Additionally, we will model the incidence of C.diff acquisition for 
intervention and control patients using Poison regression models and to determine the 
gloving impact. 
CDI Infection Rate: For unit-level data, we will compare changes in CDI infection rates between 
the intervention and control units using the chi-squares test or Fisher’s exact test with post-hoc 
pairwise comparisons. For patient-level data, infection rates will be modelled for specific time 
periods (during 3, 6, 9 and 12 months; or every 3 months of the study period [up to 24 months]) 
using incidence split modeling to determine the point of highest infection within each unit, with 
appropriate covariate adjustment. We will use the Royston’s trend test to conduct a time-trend 
analysis for CDI infection rates for specific time periods (during 3, 6, 9 and 12 months; or every 
3 months of the study period). 
Other HAI Rates: All other rates between intervention and control units will be compared using 
chi-squared test or Fisher’s exact test, with post-hoc pairwise comparisons. All incidence and 
risk analysis will be conducted using Poisson regression models with covariate adjustment. 
For specific time periods (during 3, 6, 9 and 12 months; or every 3 months of the study 
period), we will use incidence split modeling to determine the point of highest infection within 
each unit, with appropriate covariate adjustment. We will use the Royston’s trend test to 
conduct a time-trend analysis on the monthly HAI (CAUTI and CLABSI). 
 
Length of Stay: A weighted two-sample and paired t-test will be used to compare mean length of 
stay between the intervention and control units. 
30-Day Mortality: Using patient level data, we will conduct a 30-day survival analysis to 
determine the hazard of mortality for control and intervention units using a cox proportional 
hazards model with Kaplan Meier curves. Within each unit, a risk analysis will be conducted to 

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determine the predictors of 30-day mortality. Additionally, we will examine survival 
percentages at specific periods of the intervention period (i.e. 3, 6, 9 and 12 months; or every 
3 months of the intervention period) using life tables and log-rank tests to determine at which 
points mortality was highest for each unit. 
Other clinical outcomes: Rates of toxic megacolon and colectomy will be compared between 
intervention and control units using chi-squared test or Fisher’s exact test, with post-hoc 
pairwise comparisons. All incidence and risk analysis will be conducted using Poisson 
regression models with covariate adjustment. For specific time periods (during 3, 6, 9 and 12 
months), we will use incidence split model to determine the point of highest infection within 
each unit, with appropriate covariate adjustment. We will use the Royston’s trend test to 
conduct a time-trend analysis on the monthly outcomes. 
Intervention Fidelity: We will calculate the compliance rates for both the intervention and control 
units and compare them using a chi-squared test. We will conduct a univariate logistical 
regression model to determine the odds of compliance with respect to additional unit 
characteristics such as number of beds and location. Monthly compliance will be modeled using 
a time series graphing technique with trend analysis estimates. 
Isolation Days of Care: Monthly aggregate data of isolation patients will be collected from 
infection control at participating sites which are collected as standard of care and we will 
estimate the days of care by multiplying this number by the average length of stay for the 
participating unit. We will make comparisons between the intervention and control groups using 
the analysis of variance (ANOVA). 
Healthcare Worker Experience: After verification of transcription accuracy, team members will 
use VA-approved software to facilitate data organization, coding, and retrieval. Qualitative 
content analysis will inductively generate codes and categories rather than using an a priori 
coding scheme or researcher-generated coding scheme.41 Line by line coding will be conducted 
to identify codes or statements of meaning (level I coding). Codes that emerge will be grouped 
into larger categories (level II, coding for themes). 
Patient Experience: After verification of transcription accuracy, team members will use VA- 
approved software to facilitate data organization, coding, and retrieval. Qualitative content 
analysis will inductively generate codes and categories rather than using an a priori coding 
scheme or researcher-generated coding scheme.41,42 Line by line coding will be conducted to 
identify codes or statements of meaning (level I coding). Codes that emerge will be grouped 
into larger categories (level II, coding for themes). 
Cost: Descriptive statistics will be used to describe nursing time frequencies and 
percentages. Paired t-tests will be used to compare average provider time for donning and 
doffing between the intervention and control units. We will use Royston’s trend test to 
examine the monthly costs of supplies over time. 
Provider-Patient Contact Surveys: We will compare the differences in reported contact between 
the intervention and control units. 
Missing data: We will resolve all missing data using a case-wise analysis technique or multiple 
imputation solution. 
5.9 Withdrawal of Subjects 
Sites that are unable to meet performance measures such as a) obtaining a high rate of stool 
samples from admitted patients and b) collecting primary and secondary endpoint data may be 
withdrawn from the study at the PI’s discretion. 
A unit may withdraw voluntarily from the study at any point. Attempts will be made to collect all 
data for the duration of their participation in the intervention phase regardless if they were unit 
randomized to the intervention or standard care group including 30-day mortality occurring after 
participant withdraw or termination. 

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Since there is a short data collection period of only 15 months, the study team does not plan to 
replace any units who withdraw or terminate. 
 
6.1 
Reporting 
 
6.2 
Adverse Events 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). An 
adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: death, a life- 
threatening experience, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or disability, or a manifestation of a congenital anomaly/birth 
defect. An AE is also considered serious when medical, surgical, behavioral, social, or other 
intervention is required to prevent an above outcome. 
 
All AEs will be assessed by the PI using the following guidelines: 
 
• 
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially life- 
threatening or incapacitating. Of note, the term “severe” does not necessarily equate 
to “serious”. 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the 
clinician who examines and evaluates the participant based on temporal relationship and his/her 
clinical judgment. The degree of certainty about causality will be graded using the categories 
below. 
• 
Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the 
influence of other factors is unlikely. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the 
event occurred within a reasonable time after intervention). However, other factors may 
have contributed to the event (e.g., the participant’s clinical condition, other concomitant 
events). Although an AE may rate only as “possibly related” soon after discovery, it can 
be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related,” as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study participation makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of 
the trial medication) and in which other drugs or chemicals or underlying disease 
provides plausible explanations (e.g., the participant’s clinical condition, other 
concomitant treatments). 
• 
Not Related – The AE is completely independent of study participation, and/or evidence 
exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
All SAEs that are unexpected and related to the study will be reported by the study team to the 

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IRB in writing within 5 business days of the team becoming aware of the SAE. A specific 
reportable event form will contain a detailed description of the symptoms observed and the 
concomitant treatment administered. Furthermore, the report must comment on a possible 
causative relationship between the AE and the research procedures. Each SAE must be 
followed until it is resolved or can be explained satisfactorily. 
 
Any death that is unanticipated and potentially related to the research will be immediately 
reported to the IRB by the study team. 
 
6.3 
Unanticipated Problems 
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to participants or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” 
means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized. 
 
Serious Problems that are both unanticipated and related to the research will be reported in 
writing within 5 days of becoming aware of the occurrence. 
 
6.4 
Protocol Deviations 

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Protocol deviations from the VA Central IRB are considered an act of noncompliance. Protocol 
deviations must be reported within 5 days of being made aware of the occurrence if they are 
likely to substantially adversely affect any of the following: 
• 
The rights, safety, or welfare of the research participant 
• 
The participant’s willingness to continue participation, or 
• 
The integrity of the research data, including VA information security requirements 
 
7.1 
Privacy and Confidentiality 
Participant confidentiality and privacy is held in the highest regard by all study team members. 
This confidentiality is extended to cover all clinical information and testing of biological samples. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study, or the data will be released to any 
unauthorized third party without prior written approval. No individual results/PHI will be 
disclosed; only coded or aggregate data will be analyzed and only aggregate group-level data 
will be reported. Published study results will not identify individual units or subjects. 
All study staff are up-to-date on VA privacy and information security trainings, specifically in 
ethical conduct, confidentiality protection, review of medical records, mandated reporting, and 
other topics of human research protections (including the Health Information Portability and 
Accountability Act (HIPAA). New staff will not be permitted to access any study data until they 
have completed all relevant trainings. Privacy will be maintained by conducting discussions and 
assessments in private rooms. 
 
Removal of access to research study data will be accomplished for study personnel when they 
are no longer part of the research team. The Information Security Officer, Privacy Officer, and 
Associate Chief of Staff for Research will be notified immediately of any actual or suspected 
data breach. 
 
VA REDCap may be used for entering patient-level clinical data, unit-level clinical and 
observational data, patient surveys, and Environmental Service worker surveys. VA REDcap is 
a 21 CFR Part 11-compliant data capture system provided by the VA Information Resource 
Center. The data system includes password protection and internal quality checks, such as 
automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
No individual identifiers will be entered into VA REDCap, and only authorized staff will have 
access to the study REDCap project(s). No other web applications and no mobile devices will 
be used in this study. Unless otherwise specified as part of a valid DUA, no data will be stored 
on computer hard drives and sensitive data will not be removed from the VA-protected 
environment at any time; thus, no data will be stored at an alternative (non-VA) site. Original 
electronic VA data will be backed up regularly and stored behind the VA firewall. 
 
At the end of the study, all VA research data and information will be retained in accordance with 
the applicable VA Records Control Schedule (NARA RCS 10-1). Prior to any destruction of 
research records, the PI will contact the Records Management Officer for current policy. 
Records will be destroyed, when allowed by shredding (paper records) and/or in a manner from 
which they cannot be retrieved (electronic/digital records). 
Additional security measures for specific study procedures are described below. 

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Observations. We will follow usual infection control practices for observations of intervention 
fidelity/barrier precaution compliance using an audit tool. No identifiable information regarding 
the healthcare worker or the patient will be recorded, and only aggregate data will be shared 
with each site. 
 
Interviews/Focus Groups. Interviews of patients will be administered in patient rooms at the 
VA. Interviews/focus groups of healthcare workers will be conducted in private conference 
rooms and/or over the phone, with both parties in a private setting. Patient interviewers will 
undergo training around human subject’s protection, the interview guide, and engaging patients 
in a sensitive, respectful manner that promotes patients’ engagement in the interview. 
Furthermore, interviewers will participate in role playing to prepare for interviews and an expert 
qualitative researcher will observe their first actual interviews. The importance of privacy and 
discretion will be emphasized to participants during the sessions. 
Researchers will notify participants that they are recording. Participants will be asked not to 
identify their names or other identifying information during interviews. Audio files will only be 
labeled with a unique number will be generated for each patient and healthcare worker and 
linked to a different unique letter representing the hospital unit. This identifier will be for 
purposes of this study only and will not include individually identifiable private information. Data 
will be stored in a password-protected database and accessed only by approved research 
personnel via password-protected computers in locked offices. Only aggregate data will be 
analyzed and presented; patient-, worker-, or facility-specific data will not be identified. 
 
The Centralized Transcription Services Program (CTSP), based at the Salt Lake City VA, will 
transcribe interviews/focus groups. The CTSP will remove all identifying information, such as 
name or other personal identifiers, from the transcript prior to analysis. An investigator will 
upload the tapes to a transcriptionist at CTSP. Multiple levels of security will ensure the integrity 
and confidentiality of all data stored on the system. The computer system operates entirely 
within the VA network, which is protected by firewalls maintained by the VA Central Office. 
Authorized study team members are assigned an active, individually unique user identification 
code and individually unique password. The accounts and passwords comply with existing VA 
policies and procedures for computer access. User identification codes limit access to specific 
directories and files. The computer system is accessed via computers assigned to authorized 
investigators. These computers are secured through use of individually unique user 
identification codes and passwords. 
 
All audio files, field notes files, and transcript files will be stored and transferred within the VA 
network which is protected by firewalls maintained by the VA Central Office. Only approved 
study team members and transcribers will have access to the audio files. The recordings will be 
appropriately destroyed at the end of the study, and the coded transcripts will be maintained 
according to VA policy. 
 
Clinical Data Collection. Only the local site and minimum Madison staff necessary for 
replacing individual identifiers in patient-level data with the study ID number will have access to 
patient information, for example, the code key connecting patient name with the study ID 
number. All remaining data transferred to the Madison VA, including stool samples, will be 
coded. Each participant will be assigned a unique study ID, and all research data will be coded 
with ID numbers only, not names or social security numbers. The document (“key”) linking 
names and ID numbers will be stored in a separate password-protected document on a 
password-protected server, to which only essential study staff (LSI, RA, and Madison staff 
responsible for coding patient-level data) will have access. 

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Unless otherwise specified as part of a valid DUA, research data for purposes of statistical 
analysis and scientific reporting will be stored at the Madison VA hospital. All identifiable data 
will be stored in locked drawers/file cabinets in the Madison VA Research Office or on a secure, 
password-protected server space in a research folder accessible only to trained and approved 
study personnel. All research data will be de- identified (i.e., all personally identifying information 
will be removed) prior to transfer to external parties of a valid DUA, data analysis and 
manuscript preparation; all identifiers will be replaced by study ID. All documents and databases 
will be stored on a secure server behind the VA firewall, and housed within a password- 
protected folder only accessible to approved research team members (unless otherwise 
specified by a valid DUA). 
 
We will work with sites to determine their preferred method of data collection/transfer; i.e., 
whether the Madison study team will download these aggregate data from the Corporate Data 
Warehouse or whether the local study team will upload these data to the Madison study team 
using VA-secure methods behind the VA firewall. Regardless of collection/transfer method, all 
data will be kept behind the VA firewall at all times unless otherwise specified in a valid DUA. 
No study data will be shared in a non- secure manner. All data will be shared in accordance 
with VA regulations and via methods approved by the required officials (e.g., as outlined in a 
Enterprise Research Data Security Plan signed by the CIRB Information Systems Security 
Officer). All culture samples will be sent to the coordinating site at the central microbiology 
research laboratory at the Wm. S. Middleton Memorial VA Hospital. No patient identifiers will 
be received by the central laboratory, and no individual results will be shared back with 
facilities. 
 
7.2 
Specimen Banking 
Stool specimens collected during this study will not be banked. 
 
8.0 
Communication Plan 
Each participating site will have an assigned site PI (Local Site Investigator, LSI) and a 
Research Assistant (RA, 20% effort). These individuals will be responsible for 
monitoring local oversight and approvals, notifying appropriate stakeholders (including 
the facility director) about the study and its progress, and ensuring compliance to the 
study protocol. The LSI and RA will maintain a local site study binder with up-to-date 
documents and relevant approvals. The PI and Program Manager will ask the LSI and 
RA to confirm that these approvals are in place before beginning study procedures at 
the site. 
The LSIs and RAs will meet regularly with the Madison-based study team, including 
the PI and Program Manager. Regular agenda items for these meetings will include 
discussing any Serious Adverse Events, Unanticipated Problems, interim results, or 
other factors that may impact conduct of the study. Any changes to the protocol will be 
discussed during this meeting to ensure understanding and compliance with updated 
procedures. 
The Program Manager will be responsible for maintaining and updating a shared 
SharePoint site that houses up-to-date study documents, such as the protocol. Approved 
site personnel will have access to this SharePoint so that they can access the most 
current versions as needed. The Program Manager will notify site personnel by email if 
new documents have been added or if versions have been updated on SharePoint. The 
LSI and RA will be responsible for updating local binders (digital and/or physical) as 
required and reporting any changes or issues to the PI and Program Manager. 
Site participation will end at the close of the up-to-24-month intervention period and 

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once all HCW and patient interviews have taken place at the site. At that point, we will 
notify the LSI and the facility director in writing that the study procedures at this site 
have ended. 

VA Central IRB 
Effective Date: 
May 7, 2024 
 
9.0 
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