A Double-blind Randomized Placebo Controlled Clinical Trial Evaluating Effect of Chlorhexidine Gluconate 2% Cloth vs Placebo Cloth Baths on the Incidence of Central Line-Associated Blood Stream Infections in Outpatient Hematopoietic Stem Cell Transplant Patients
Phase: PHASE2
Conditions: Stem Cell Transplant Complications
Sponsor: University of Chicago

Double-blind Randomized Placebo controlled Clinical  trial evaluating effect of 
Chlorhexidine Gluconate 2% cloth baths vs Placebo cloth baths on the incidence of 
CLASBI in Outpatient HSCT Patients. 
 
PI: Kathleen Mullane, D.O. 
Sub I: Jennifer Pisano, M.D. 
 
 
NCT03030989 
 
December 22, 2016 
 
 

Double-blind Randomized Placebo controlled Clinical  trial evaluating effect of 
Chlorhexidine Gluconate 2% cloth baths vs Placebo cloth baths on the incidence of 
CLASBI in Outpatient HSCT Patients. 
 
PI: Kathleen Mullane, D.O. 
Sub I: Jennifer Pisano, M.D. 
Section of Infectious Diseases and Global Health 
Immunocompromised Host Service 
 
Introduction: 
Central line associated blood stream infections (CLABSIs) are one of the most deadly 
types of hospital-acquired infections (HAIs), with a mortality rate of 12% to 25%.1  
Nationally, hospital acquired CLASBIs are reported as a measure of patient safety 
through the National Healthcare Safety Network.  The Center for Disease Control and 
Prevention (CDC) collects data and reports on CLABSIs among hospitalized patients 
aged 1 year or older and among patients receiving outpatient hemodialysis.2  It is 
estimated that 84,551 to 204,901 CLABSIs occur each year resulting in 10,426 to 
25,145 preventable deaths.3  The cost of each CLABSI is estimated to range from 
$3,700 to $45, 254.4  If the average mortality caused by CLABSIs is 18% (reported 
ranges 15-24%) and the average CLABSI rate is 5.3 per 1000 catheter-days, as many 
as 28 000 patients die of CLABSIs annually in ICUs alone.3-5  Because of the high 
incidence, mortality rate and healthcare costs of CLABSIs, the Agency for Healthcare 
Research and Quality (AHRQ)  sponsored a national patient safety imperative aimed at 
eliminating CLABSIs.4  This program reviewed data from over 1000 hospitals in 44 
states in the US including ICU, non-ICU and pediatric unit settings.  It implemented a 
Comprehensive Unit-based Safety Program (CUSP) directed towards reducing central 
line associated blood stream infections.  The program bundled interventions of 
establishing safety cultures on a unit level with utilization of safety teams and 
implementation of CLABSI reduction steps.  These CLABSI reduction steps included: 
appropriate hand hygiene, full barrier precautions with line insertion, daily review of line 
necessity, chlorhexidine skin care, and avoidance of femoral site placement of central 
lines.  With use of these methods, CLASBI rates were reduced 40%.6  While much of 
healthcare is being diverted to the outpatient setting, no such efforts have been 
undertaken in evaluating outpatient CLABSIs with the exception of the dialysis 
population. 
  
Individuals undergoing hematopoietic stem cell transplantation (HSCT) usually require 
central venous access for frequent infusions including chemotherapy and blood 
products as well as for hydration, electrolyte replacement, antibiotics, and parenteral 
nutrition.  However, the benefits of having a central line must be balanced against the 
risk of complications, the most common of which is central line-associated bloodstream 
infections (CLABSIs).7-9 Risk factors established for the development of CLASBI include 
prolonged hospitalization before catheter placement, prolonged duration of 
catheterization, microbial colonization of the insertion site or catheter hub, internal 
jugular or femoral catheterization, neutropenia, TPN, transfusion of blood products and 
frequent manipulations of the catheter. (10-16) Care of patients undergoing a HSCT is 

complex and these individuals collect many of the known factors, which put them at risk 
for developing CLASBIs.  As well, chemotherapy often induces mucositis resulting in 
translocation of enteric microorganisms into the bloodstream, which may then 
secondarily seed central venous access devices.17,18 In an effort to reduce bacteremia 
in HSCT patients expected to have a prolonged period of neutropenia, antimicrobial 
prophylaxis with agents having activity against enteric pathogens is common practice.  
 
With engraftment, the absolute neutrophil count rises, prophylactic antimicrobials are 
discontinued, and mucositis resolves.    HSCT patients may be released to home 
requiring infusion of fluids, electrolytes, TPN, and sometimes antimicrobial agents.  As 
well, these patients have frequent outpatient visits for transfusion of blood products.  
Due to chemotherapy induced phlebitis of peripheral veins, the central line is frequently 
the only intravenous access available to obtain blood for laboratory monitoring of the 
patient.  Therefore, patients who have undergone HSCT have multiple persistent risk 
factors for the development of CLABSI, even after discharge from the inpatient setting. 
 
Chlorhexidine is a broad-spectrum antiseptic agent active against both gram-positive 
and gram-negative bacteria as well as yeasts, and has been successfully assessed as 
an effective skin antiseptic alone or in combination with alcohol.19-29   Due to its success 
in reducing hospital acquired CLABSIs, daily chlorhexidine baths have been 
implemented in the intensive care setting and in inpatient stem cell transplant units.  In 
this study we aim to evaluate whether or not continued skin decontamination with 2% 
chlorhexidine impregnated washcloths, used after routine bathing, will reduce the 
incidence of CLASBIs in the HSCT population after discharge for as long as the central 
line is in place or 14 weeks post discharge, whichever comes first. 
 
 
Overall Study Design: 
This will be single site [University of Chicago (U of C)] prospective, double blinded 
randomized, controlled clinical trial of daily bathing with no-rinse, 2% CHG-impregnated 
washcloths (Sage 2% chlorhexidine gluconate cloths; Sage Products Inc., Cary, Illinois) 
vs placebo chlorhexidine washcloths. The main study outcomes will be primary BSI and 
clinical (culture-negative) sepsis.  Catheter insertion policy for the U of C HSCT program 
mandates interventional radiology insertion of central venous catheters on the day of 
admission for HSCT conditioning using sterile technique, full barrier drapes, and 
insertion site disinfection with 2% CHG.  Antiseptic- or antibiotic-coated catheters are 
not used. While hospitalized, patients follow routine daily 2% CHG baths.  Routine 
catheter care with CHG-Alcohol (Chloraprep) dressing changes and a CHG-biopatch at 
the insertion site will be done weekly, per standard of care, while inpatient and will 
continue in the outpatient setting.  Prior to discharge, enrolled subjects will be 
randomized to 2% CHG vs placebo washcloths (supplied as a blinded product) which 
the patient will continue until end of study.  No other catheter-associated BSI infection 
control interventions will be implemented during the study. 
 
Setting and Participants: 

Approximately 200 HSCTs are done annually at the U of C. On admission for transplant, 
HSCT patients commence use of daily 2% chlorhexidine applied by impregnated 
washcloths after routine daily washing.  This is done as part of standard care in an effort 
to prevent inpatient CLASBIs.  Once patients have demonstrated engraftment of 
neutrophils (absolute neutrophil count >500 cells/mm3 for 48 hours) routine home 
bathing instructions are given by the nursing staff in preparation for discharge.  These 
instructions include educating the patient specifically not to allow the central line 
insertion site to become wet (i.e.: no showers or baths), technique for scrubbing the 
catheter hub(s), and sterile technique for accessing the line in those who will be 
performing home IV administration.   
 
The incidence of inpatient hospital acquired (HA) and outpatient present on admission 
(POA) CLASBIs as evaluated here at the U of C (see table below) has been previously 
determined and the outpatient data will be used as our initial data control group: 
 
 
Number of CLABSI by 
Nursing Unit 
 
 
September 2007 to August 
2008 
 
Unit 
Number of    HA-CLABSI 
Number of 
POA-
CLABSI 
T6NW 
32 
18 
T6NE 
1 
30 
T6SW 
3 
28 
TOTAL 
36 
76 
 
 
Methods: 
Approval of the study protocol will be obtained from the University of Chicago 
Institutional Review Board. 
 
Subjects: 
Approximately 200 HSCT subjects will be enrolled 
 
Inclusion Criteria: 
Each patient admitted to the U of C HSCT unit aged >18 years during the study periods 
will be approached regarding the study. 
 
Exclusion Criteria: 
Patients who have already experienced an allergy or rash related to use of 
chlorhexidine washcloths or other CHG products will be excluded.   

 
Patients with extensive open wounds will be excluded from the study. 
 
Study Procedures: 
Prior to discharge, eligible subjects will be approached for study participation.  Those 
who agree to participate and complete the consent process will be randomized to the 
active or placebo study arms.   
 
Study Washcloth (2% CHG and placebo) : 
Subjects will receive an instruction sheet that illustrates where to use the washcloths.  
Use of the washcloths will be done in the following sequential order to rinse all body 
surfaces, with the exception of the mucous membranes of the eyes and mouth.  
First: neck, shoulders and chest; Second: axillae, arms and hands; Third: abdomen then 
groin and then perineum; Fourth: right leg and foot; Fifth left leg and foot and the 
Sixth:back of the neck back and buttocks.  
 
Subjects received education on using chlorhexidine washcloths throughout the 
hospitalization for their HSCT and prior to discharge from the inpatient hospitalization, 
therefore oversight of the trial will not include direct observation of bathing.  There will 
be no washout period in the transition from the inpatient setting.  
 
The dates of catheter placement will be recorded and used to calculate length of 
catheter days in place.  The discharge date and discharge setting will be recorded.  
Data will be recorded in RedCap.   
 
Data on all positive blood cultures will be collected for bacterial/fungal pathogens. 
Incident bacteremia (or fungemia) will include only the first episode of bacteremia / 
fungemia and will not include duplicate organisms or subsequent infections as the 
primary aim of the study is to prevent the incident CLABSI.  A bacteremia / fungemia will 
constitute treatment failure.  Subjects will stop study product and be followed for 4 
weeks for safety assessment (incident of adverse event associated with study product).  
Hospital admissions will be recorded.  Association with study product will be 
determined.  Cost of hospitalizations related to CLASBI will be determined.   
 
A study diary will be used by subjects to confirm compliance with daily bathing.  The 
study staff will ensure the subject is using the proper bathing technique at each weekly 
visit.  This document will be reviewed and collected weekly when the subject comes for 
routine outpatient central line catheter care.  The study diary will also capture 
compliance with the outpatient central line accessing protocol.   As the subject will 
access their line using the standard practice (sterile technique with chlorhexidine-
alcohol preps) the study will collect the data on this process.  Additionally subjects will 
be asked to save all packaging from washcloths used each week and bring this 
packaging to the weekly outpatient visit.  This will allow study staff to note compliance 
with washing and  to ensure subjects have an adequate supply of washcloth packages. 
The study staff will enter the total quantity of washcloth packages used during the week 
on a compliance monitoring worksheet.  

 
Length of Study Participation: 
Participation will begin at the time of consent prior to discharge.  Subjects will use the 
study washcloths while the central line remains in place or until 14 weeks post HSCT 
discharge, whichever comes first.   
 
Stopping Rules: 
Subjects that are diagnosed with a bacteremia or fungemia will stop use of product after 
a positive result. 
 
Payment: 
Subjects will not receive any payment for participation in the study 
 
Statistical Plan and Considerations: 
The plan is to accrue up to 200 subjects, however, after the first 100 subjects complete 
the study, the data set will be locked and unblinded and the incidence of CLABSIs in 
each group will be determined.  If the difference between the groups is highly 
statistically significant, (P < 0.001), the study will be halted.  A ‘Student’s’ t Test will be 
used to determine difference in outcome (bacteremia or no bacteremia) between the 
two groups. 
 
Assuming that the outpatient setting would have a higher incidence of CLABSI given the 
previous Infection Control snapshot, recalculating with an ~50% higher outpatient rate, 
the estimated number of patients would be calculated as: 
. sampsi 0.12 0.0485, power(0.8) 
Estimated sample size for two-sample comparison of proportions 
Test Ho: p1 = p2, where p1 is the proportion in population 1 
                    and p2 is the proportion in population 2 
Assumptions: 
         alpha =   0.0500  (two-sided) 
         power =   0.8000 
            p1 =   0.1200 
            p2 =   0.0485 
         n2/n1 =   1.00 
 
Estimated required sample sizes: 
            n1 =      263 
            n2 =      263 
 
For our evaluation we based the numbers of patients on the number of HSC transplants 
performed annually with a reasonable period of time to enroll subjects.  Interim analyses 
will be performed early on to see if a significant difference exists in making it appropriate 
or not appropriate to continue 
 
Risks and Benefits: 

This clinical research involves minimal risk to the patients involved since it involves only 
the use of two FDA approved bathing products. Potential recognized risks of bathing 
with chlorhexidine include local skin irritation, allergic reaction and irritation of mucous 
membranes. The FDA has waved requirement for an IND. 
 
Data Handling and Record Keeping  
All data collection files will be password protected and stored on computers belonging to 
study investigators. Data collected will be entered into the password protected Access 
database.Personal health information will be maintained with the database during study 
period, microbiology data, and medical record review. All patients will be assigned a 
unique study identification number. This number will be accessible only to study 
investigators and study staff. Any hard copies of datasets will be stored in a locked filing 
cabinet in the Infectious Diseases Clinical Trials office. After all data are collected, 
analyzed, and published, linkage between patients and their unique identifier will be 
destroyed, with the exception of data collected through Infection Control Departments 
as part of hospital operations. Identified datasets related to infection control activities 
will be maintained at the primary institution according to hospital operations policy. 
 
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