SQ53 Disinfectant Wipes for Prevention of Catheter Related Blood Stream Infection in Patients Receiving Home Parenteral Nutrition: A Single Blind Randomized Placebo-controlled Clinical Trial
Phase: NA
Conditions: Catheter-related Bloodstream Infection
Sponsor: The Cleveland Clinic

STUDY PROPOSAL
Title: Sq53 disinfectant wipes for prevention of catheter related blood stream
infection in patients receiving home parenteral nutrition:
A Single Blind Randomized Placebo-controlled Clinical Trial
(NCT048224671
Principal lnvestigator: Donald F. Kirby, MD
Co-investigators: JiSeok Park MD, Mohamed Tausif Siddiqui, MD, Kristin lzzo, RD, Sara yacyshyn, MD,
Allison Doriot, RD, Kent Aje, MD, AnilVaidya, MD, Ann Dugan, RN, Kathleen Tushar, RN, Julie Halaszi,
RN, Eileen Hendrickson PharmD, Elizabeth Gallant, RD, Samantha Kroger, NP, Nathan Rao, pA.
Introduction
Parenteral nutrition (PN ) therapy is an essentialcomponent of medical management of patients suffering
from intestinal failure. Depending on the underlying etiology and the type of intestinal failure, the
duration of parenteral nutrition therapy could range from several weeks to several years, although a
substantial proportion of these patients also require lifelong parenteralnutrition support. These patients
continue the inf usion of PN at their homes and are managed by the Cleveland Clinic's Home pN support
team. These patients require CentralVenous Catheters (CVC)for prolonged period of time for infusion of
parenteral nutrition. The two most commonly used centralcatheters forTPN infusion are the peripherally
lnserted CentralCatheter(PICC)andTunneled CVCs. Catheterrelated blood stream infection (CRBSt) is a
major complication of long-term CVCs. CRBSI is associated with high morbidity, mortality and healthcare
Protocol version : L27.2022

cost. Additionally, CRBSI can also lead to an interruption in nutrient delivery, loss of work and productivity,
premature vascular access device removal, and poor quality of life.
Prevention of CRBSI is an important component of clinical management of patients receiving home PN
therapy, Severalstrategies have been adopted to reduce the incidence of CRBSI. A heparin lock solution
was used in the past for many years; however, current nutrition society guidelines recommend normal
saline locks instead of heparin locks. Published data has suggested that heparin locks have not proven to
have a substantial effect on CRBSI prevention, and it paradoxically increases the infection risk due to
biofilm production. Antibiotic locks have also been used, although this practice is largely not prefened
due to increased risk of infections with resistant microorganisms. Taurolidine is another lock solution
which has been studied in the countries outside the United States such as Canada; however, it has not
been approved for the use in the U.S. yet.1
We currently use the ethanol lock therapy which consists of 2ml of SU/o ethanol. Multiple single center
studies, meta-analysis and the systematic reviews have reported the effectiveness of ethanollocktherapy
in prevention of CRBSI. ln a retrospective study on the cohort of PN patients f rom the Cleve land Cliniq we
found that Ethanol Lock therapy (ELT) was associated with a decrease in the number of CRBSI-related
hospitalizations (10 vs 6 per L00O catheter days), reduced number of confirmed CRBSI diagnoses with
positive culture (3.5 vs L.6 per 1000 catheter days) and decrease in the number of new catheter
requirements.2A study by Zhang et al. reported in their systematic reviewthat ethanol lock was associated
with lower CRBSI rates when compared to heparin or normal saline lock.3
By strategically using the ethanol lock therapy daily in our home PN patients, we have b een successfu I in
reducing the incidence of the CRBSI in our patient population. However, ethanol lock solution will no
longer be available to our patients due to changes in the supply network. The sterile ethanolsolution b
redirected to a breakthrough use for patients with cardiac hypertrophy which has driven its cost
substantiallyhigh. OurcenterhadearlierreportedaspikeinCRBS|inourpatientswhentheethanollock
solution became unavailable temporarily due to national shortage.aTherefore, it is veryimportant to
study and to assess the effectiveness of newer strategies for prevention of CRBSI.
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SQ5-3 is a novel antimicrobial, sporicidal aqueous solution that is based on a platform of quaternary
ammonium chloride compounds. Otheractive components include polymeric biguanide, chlorocresol,
bronopol and ethanol. lt has beentested against a wide range of bacteria, viruses, spores and fungal
pathogens. Extensive laboratorytesting has demonstrated the effectiveness of Se53 impregnated wipes
in cleaning surfaces including catheters over a 24 hour plus time period. ln addition, it includes no
development of VN BC (Viable-but non culturable bacterialcolonies) populations or evide nce of resistance
to the active compounds. SQ53also received an in vitro evaluation of the irritancy potentialusing a tissue
engineered human skin model and was found to have no potential for skin irritation. ln Europe, Se53
currently has a class 1CE mark and is cleared and registered underEuropean Union Biocidal product
Regulations in UK, Germany, France, Belgium and Austria. SQ53 is available as a single wipe per pack which
is prepared in biocide driven sterilized environment. The pack is easyto open by tearing off the top end
and presenting the contents to the operator to remove under sterile conditions.
SQ53 has been studied in lndia in 148 patients in two grou ps. G roup t had the patients who required long
term CVCfor PN (n = 42,37 adults and 11 pediatric patients) and dialysis (n=106). Group 2 had the patients
who required PN for short duration for postop complications (n=14). The study findings (which are in the
publication process) support a substantial improvement in the CRBSI rates from 131 episodes per l{XX)
(tt8 per 365 days) days to 9 episodes per lfiD (3 episodes per 355 days) resulting in an overall gttyo
reduction. None of the enrolled patient's experienced local or systemic adverse effect with the use of
SQ53 wipes.
Study significance:
t' Ethanol Lock Therapy (ELT) which is currently used for prevention of CRBSI is an off -labelusage of
a commercially available product that will no longer be readily available for patients receiving
home parenteral nutrition. Anothe r breakthrough use of ELT has precluded the possibility of ELT
usefor PN patients.lt is critical to identifyand explore otheragentsand alternatetherapeutic
Protocol version : 1.27.2022

approaches to prevent excess morbidity and mortality resulting from preventable CRBSI. SQ53
has shown promising results in CRBSI prevention trial conducted outside the United States.
2. The currentstudywill be a randomized single-blinded placebo-controlled phase lll clinicaltrial for
this lnvestigational new device (SQ53 wipes) intended for the catheter cleaning in patients
receiving home parenteral nutrition.
3. With ethanol lock therapy being phased out, there is no currently approved effective and readily
available modality available in the United Statesto prevent CRBSI. On compassionate grounds it
is imperative to use and to study SQ53 so that patients can benefit from this clinicaltrial.
Protocol ve rsion : 7.27.2022

Study design: Prospective randomized single-blinded placebo-controlled clinicaltrial
Yes
Yes
No
* Please note that the randomization will also be stratified by PICC/Tunneled catheter type
Home Parenteral Nutrition Patient pool
Total N = 304
lnform patients about the cllnical trlal: send letters
Current patient pool
High risk patients: N = 68 (22 %)
Low risk patients: N = 236 (78 %)
And all new
to call in to enroll and discuss with HPN team
lnterested
Obtain informed consent for
study enrollment / Docusign
Not enrolled
in the study
Continue
standard of care
Enrolled in the study
Stratified Randomization by pharmacy
High risk - Low risk - New patients
Treatment Group
Use SQ53 as prescribed
Placebo Group
Use Alcohol wipes as
Continue wipes use
for 6 months
lnterim analysis of the data (Pcr protocol & lntention to treat analysis)
-Calculate CRBSI rates per 1000 catheter days: Treatment vs placebo group
-Measure other outcomes: CRBSI admissions, Catheter exchange, Adverse Effects
-Stratified analysis with patients used as lheir own controls
-Compare CRBSI rates with other historical cohorts reported in other studies
- Lower rate of CRBSI in study group
- No major adverse effect
Discontinue the trial
Continue the trial for another 6 months
Enroll additional patients
Final Endpoint
Re-analysis of dala
Protocol version : 1.27.2022

Study obiectives:
Primary obiective:
1. To determine the effectiveness of SQ53 wipes in prevention of CRBSI in patients receiving home
parenteral nutrition.
Secondary obiectives:
I. To identify if there are any major or minor adverse effects such as skin irritation associated with
the use of SQ53 wipes.
lnclusion criteria and patient recruitment:
1. Adult (age>18) patients requiring home parenteralnutrition supportvia PICC line or tunneled CVC.
2. Patients will be included via following process:
a. All patients managed by CCF HPN team, meetingthe inclusion criteria will be sent a letter
of information and full informed consent form.
i. Letter of information will be a cover letter informing patients about the clinical
trial ( lette r attached)
ii. lnformed consent form: Standard informed consent form with detailed
information about the study as per the Cleveland Clinic guidelines.
iii. Letters will be sent in an alphabetical order for 10-15 patients each week to
evenly distribute the work burden overtime.
b. Patients who are interested to enroll in the study will call our HPN team, and we will
answer any questions that these patients might have.
i. The consent form will be again sent via email.
ii. HPN dietitian will take consent over the phone by using DocuSign and will
document it in patient's chart in HPN database
iii. HPN dietitian will notify caring NST physician regarding patient's enrollment in
the trial.
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c. HPN dietitian (or NST physician or both)will classify patient in eithera High Risk, Low Risk
or New Patient Category via specific criteria.
i. ldentification of high-risk patients which will be determined by the following
crite ria:
L History of one or more CRBSI infection in the past 6 months
2. lmmunocompromised state increasing the infection risk
a. Clinical determination based on comorbidities such as HlV,
immunosuppressant medications, and steroids (prednisone
>40mg per day)
3. History of multiple catheter exchange in the past (greater or equalto 2
within the past 5 months) with difficult access
a. This determination to be made based on patient's history
ii. ldentification of Low risk patients:
t. Patients who do not meet High-risk criteria will be classified as Low risk
patients
iii. New patients:
t. New patients are the patients who are newlystarted on PN during their
in-patient stay and those who have been on PN less than 6 months unhs
they had CRBSI in the time frame.
2. These patients will receive information about the clinical trial by RNs who
provide education as standard of care.
d. Patients can also be enrolled in the study at the time of outpatient visit, or before
discharge from the hospital.
3. Cleveland Clinic Home lnf usion Pharmacy (CCHIP)will be informed about patient's enrollment and
the risk category (High vs Low vs New patient) and the catheter type (PICC or tunneled)
a. CCHIP will perform stratified randomization and assign the patient to either Treatment
(5453) or PLACEBO (Alcoholwipes) group.
4. Treatment group will also have the SQ53 impregnated wipe used on a remote site to check for
hypersensitivity and any otherskin reactions before it is be deemed safe to use routinely in that
patient.
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5. All enrolled patientwill needto agreeto reach outto Home Nutrition Pagerwhich is available
24x7 in case of noted adverse effect - this is standard of care for home PN patients.
Exclusion criteria:
1. Age less than 18 years
2. Women known to be pregnant (patient will be asked verbally- no pregnancy test will be
performed)
3. Women of childbearing age who are planning a pregnancy
4. Women who are breastfeeding
5. Patient's refusalto enroll in the study at any point in time
5. Patients who refuse to use disinfectant wipes daily.
7. Patients who use port for their PN infusion.
8. Patients who are enrolled in other clinicaltrials with investigational drugs or device
Blinding and Randomization:
Blinding:This will be a single blinded study and the NST-providers willbe blinded to the treatment
arm that the patient is assigned to. A clinician will initially interview the patient and at the time of
enrollment into the clinical trial, obtain an informed consent after which the patient will be
enrolled in the study.
Blinding the patients is not possible due to several reasons:
o SQ53 and alcoholwipes will have labels on them
o differences in physical characteristics (smell) which are distinct for alcohol wipes and
sQs3
o therefore, it is unfeasible to blind patients to the intervention.
However, despite beingan unblinded study, outcome of our study is not likely to be affected as
the primary outcome measure is diagnosis of CRBSI which is based on the Positive Blood Culture
and is not very likely to be impacted by a placebo effect.
Randomization with a placebo: Once patients are enrolled into our study, patient's information
will be discussed with the pharmacy who will assign the patientto either a treatment or a placebo
group.
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Patients will be randomized in 1:1 ratio to receive either Se53 or placebo. The randomization
process will be stratified randomization, followed by blocked randomization in each stratum.
Stratification will be done on two factors: CRBSI risk category and catheter type. CRBST risk
categories will be determined by the clinicians or NST staffs 1. High risk (1 or more CRBST in
previous 6 months) 2. Low risk (no CRBSI in previous 6 months 3. New patient. Cathetertypes will
be 1. Tu nneled ce ntral catheters 2. N on-tun neled central catheters. The design has 3 x 2 = G strata.
Blocked randomization will subsequently done in orderto avoid serious imbalance in the number
of participants assigned to treatment or placebo group. The block sizes will be determined by
Cleveland Clinic Home lnfusion Pharmacy.
Intervention:
Patients who qualifyto enrollin the trial and sign an informed consent will be enrolled and will be eligible
to receive either the intervention or the placebo. Providers will be blinded to which group patient is
assigned to.
Pharmacy (Cleveland Clinic Home lnfusion Pharmacy will perform randomization and will
assign patients to the groups)
All patients in the study will receive the wipes (Treatment group = Se53 wipes, placebo =
alcoholwipes)
o Provide packs of sterile wipes to the patient for dai[ use (external use only)
o wipes should be used daily, as well as, when the dressing is changed, by wiping the
catheter surface and hubs for at least 15 seconds
o Daily use: Patientswill be given instruction to clean the exteriorandthe caps of the
intravenous catheters by following a sterile technique. This should be done before
and after each use (i.e. PN infusion)
o At the time of dressing change: Standard practice is to change the dressing every
week. At this time the patient will use wipes to clean the catheter exit site and skin
around the catheter exit site, catheter exterior and catheter caps prior to applying
the new dressing
o Wipes will be provided to the patientfree of cost (material will be sponsored bythe
JVS company)
Protocol version : !.27.2022

Patients in both the groups will continue to use the standard care: i.e. ethanol (curos) caps,
saline locks.
Data collection:
1. A registry of enrolled patients will be prepared. CCF HPN service has an approved database of
patients receiving home parenteral nutrition. There are no additional HPI that will be collected
as a part of enrollment in the study. The patient data is already collected into a password
protected HPN database as current standard of practice. This data is routinely collected and
updated by HPN dietitians.
Sample data sheet of primary objectives (data in italics blue font is for example):
Patient Nomenclature:
SQs3/Treatment G roup: Pati ent T1, Patie nt T2....
Placebo Group: Patient C1, Patient C2....
Pre vs Post
SQ53 trial
enrollment
Number of
Confirmed CRBSI
in 6 months
Number of total
admissions for CRBSI
in 5 months
Number of catheters
changed due to CRBSI in
5 months
Patient T1
Post
o
7
0
Patient T2
Post
Patient Cl
Post
1
1
1
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Patient C2
Data protection, processingand, analysis ofthe data:
1. CCF HPN service has an approved database of patients receiving home parenteralnutrition. The
patient data is already collected into a password protected HPN database as current standard of
practice. We will use REDCap for data entry for analysis. All data will be password protected.
2. we plan to perform both "Per Protocol" and "lntention to treat anatysis".
3. Patients whose compliance is less than 90 percent will be excluded from Per Protocol analysis;
however, those patients will be accounted in intention to treat analysis. Patients who developed
skin reaction in remote site (e.g., forearm) will be excluded from Per Protocolanalysis, but will be
included in intention to treat analysis
a. Compliance will be determined by HPN dietitian at the time of phone/virtual visit
encounters: patient will be asked about their disinfectant wipe use and compliance.
4. Our primary outcome measure (as listed in above data sheet)willbe differences in the CRBSI rate
at 5 months after patient enrollments into the trial (i.e. Se53 use). We will also perform sub-
analysis by utilizing patients as their own controls. Please see the detailed timeline below.
5. We will also analyze the differences in the numberof admissions forCRBSt (which would include
admission with suspect CRBSI), as wellas, overall number of catheters changed for confirmed and
suspected CRBSI.
6. We will perform Poisson Regression analysis to compare the rates and 95 % confidence interval
of the differences in CRBSI rates and CRBST admissions.
7. We will also perform a descriptive analysis identifying the most common microorganisms causing
the CRBSI in the periods both before and during the Se53 therapy.
8. We will also perform a survival analysis to plot a Kaplan-Meier curve
Protocol ve rsion : t.27.2022
Post
Post
Patient C3

9. We will collect mortality data of patients. We will report an overall mortality, as well as, CRBSI-
specific mortality in patients using SQ53 for CRBSI prevention.
Sample size and power calculation:
t. ln the un-published study conducted in lndia SQ53 has been reported to reduce the CRBSI rate by
94%. We expect this effect size to be lower in our cohort. We performed our sample size
calculation by utilizing the data reported in our previous study which reported CRBSI rates in high
risk PN patients (Pre-ELTCRBSI rate= 3.53and post-E1T1.65 per1,fi)0 catheterdays). Considering
current CRBSI rate in our high-risk population to be 1.65 per 1000 catheter days, we will need a
sample size of 45 patients to identify a 50% reduction in CRBSI rate with alpha of 0.05 and 80 %
power.
2. To account for the patient attrition due to mortality, lost follow up and non-compliance (for per-
protocol analysis), we would like to increase our sample size by 307o tothis estimated calculation
and would need to enroll 30 patients in each group of our study to make determinations of
differences with statistical significance.
Safety concerns: Risk to the study participants: Minimal
1,. Our study is a single blinded randomized placebo-controlled phase lll clinical trial which utilizes
disinfectant wipes which are meant forexternaluse only. These wipes have proven to be safe in
the in-vivo and in-vitro studies.
2. No major adverse effect has been reported in previous clinicaltrial.
3. Current data suggest that SQ53 has no potential for skin irritation; however, if a patient
experiences hypersensitivity skin reaction to any of the ingredients in the formula, then those
patients will be excluded from the study and use of wipes will be discontinued.
4. Collected PHI data will be securely protected on the Cleveland Clinic Network drive.
Timeline:
Please see below a simplified timeline for this project.
Time Period
Activity
Protocol version : I.27.2022

Project Lead: Donald Kirby
Project mentors: Gail Cresciand Mandy Corrigan
Project team members: Mohamed Tausif Siddiqui, Allison Doriot, Ji
Seok Park and Richard Benjamin, Eileen Hendrickson, AnilVaidya
June 2020 - Sept 2020
1. Protocoland team development-
2. lnvestigational New Drug (lND exemption process)
3. FDA exemption given by CCF IDE office considering
the wipes as low risk device
Personnel responsibility:
Above steps have been completed
Oct2O2O - Nov 2020
1. Protocol submission to CHN & budget acquisition
2. Protocolsubmission to DDSI
3. Protocolsubmission to IRB
Personnel responsibility:
Above steps have been completed
Protocolfor IRB/CHN/DDSI submission is ready
Cover lefter is ready
lnformed consent document is ready
Budget is done
Nov 2020 -Dec2O20
1. Once IRB is approved: send lefters to patients
2. Obtain informed consent and enrollpatients
3. Risk category assessment
4. Baseline data collection
5. Randomization
6. Shipment of SQ53 or Placebo supply
Personnel responsibility:
1. Sending lefters to patients:
- Letter has been drafted and ready, to be printed and
mailed to the patients by study coordinator
Protocol ve rsion : 1.27.2022

2. Obtain informed consent
- HPN dietitian
3. Risk category assessment
- HPN dietitian & NST staff
4. Baseline data collection
- HPN team, Nutrition Fellows, Study coordinator
5. Randomization
- DDSI statistician / CC Home infusion Pharmacy
6. Supplying SQ53 and placebo wipes
- CC Home infusion pharmacv
Dec2O2O to June 2021
1. Continuation and monitoring phase ot the study
2. Answer patient's concerns and collect data regarding
specific side effects (if any)
3. Continue standard routine follow up: i.e. with labs, or
during phone encounters
Personnel responsibility:
- HPN dietitian, NST staff and Nutrition fellows
June2021
1. Perform interim analysis of the data
Personnel responsibility:
- DDSlstatistician
July 2021to Dec 2021
L Continue the study for another 6 months and continue
to enroll the patients
Personnel responsibility:
- HPN dietitian, NST staff and Nutrition fellows
Jan2022
1. Final Analysis of the data
2. Reporting of the study findings
Personnel responsibility:
- Statistical analvsis: DDSI statistician
Protocol ve rsion : 1.27.2022

Reporting: All investigators
References
L John BK, Khan MA, Speerhas R, et al. Ethanol lock therapy in reducing catheter-related
bloodstream infections in adult home parenteral nutrition patients: results of a retrospective
study. JPEN J Parenter Enteral Nutr. 2012;36(5):603-610. doi:7O.L177/07486O71LL42U52
2. ThangJ, Wang B, WangJ, Yang Q. Ethanol locks forthe prevention of catheter-related infection
in patients with central venous catheter: A systematic review and meta-analysis of randomized
controlled trials. PLos one. 2019;14(9):e0222409. published zoLg sep Lz.
d oi:LO. I37 L / jo u rn a l. po n e .O2224O8
3. Corrigan M, Kirby DF. lmpact of a national shortage of sterile ethanol on a home parenteral
nutrition practice: a case series. JPEN J Parenter Enteral Nutr. 2Ot2;36(41:476-48O.
d oi :tO. Lt7 7 / OI486W 7 Ll 428 453
Protocol ve rsion: L27.2022