Study on the Effect of the Universal Decontamination With Daily Bathing With 4% Chlorhexidine Gluconate on the Incidence of Hospital Acquired Infections in Intensive Care Units
Phase: PHASE4
Conditions: Hospital Infection
Sponsor: University Of Perugia

                                 
STUDY PROTOCOL
Study on the Effect of the Universal 
Decontamination with daily bathing with 
4% Chlorhexidin gloconate on the 
Incidence of Hospital Acquired Infections 
in Intensive Care Units.
Study code
DUCLOREXINT
Version 1, April 27th, 2015
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CLINICA DELLE MALATTIE INFETTIVE
Direttore: Prof. Franco Baldelli
Università degli Studi di Perugia
Dipartimento di Medicina
Azienda Ospedaliera di Perugia 
 Dipartimento di Medicina Interna  
e Medicina Specialistica II
Staff Medico
Dott.ssa Barbara Belfiori
Dott. Giuseppe De Socio
Dott. Francesco Di Candilo
Dott. Maurizio Fiorio
Prof.ssa Daniela Francisci
Dott.ssa Lisa Malincarne
Dott.ssa Maria Vittoria Moretti
Prof.ssa Maria Bruna Pasticci
Dott. Daniele Rosignoli
Dott. Claudio Sfara
Dott. Andrea Tosti

                                                  
Table of contents

Introduction.

Aims of the study. 

Definitions and methods.

Study design.

Study population.

Data analysis.

Criteria and methodology of data collection.

Informations to patients.

Results publication.

Ethical considerations.

Bibliography.
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Introduction 
All hospital-acquired infections (HAI) and  especially, HAI due to
multi-drug resistant (MDR) micro-organisms are, nowadays, one of
the most relevant matter of concern because of their clinical and
economic consequences [1-2]. 
Several infection control measures (sistematic careful hand hygiene,
selective  and  universal  decontamination,  etc…)  have  been
investigated  for  their  effect  on  HAI  acquisition  rate  [3-6].
Chlorhexidine gluconate-based universal decontamination appear to
be a promising strategy [8], but other studies didn’t support these
findings [8]. 
Aims of the study
Main aim:
Evaluation  of  the  effect  of  daily  bathing  with  4%  chlorhexidine
gluconate  (CHG)-containing  soap  on  the  incidence  of  HAI  in  2
intensive care units. 
Secondary aim:
Evaluation, if possible, of the effect of daily bathing with 4% CHG-
containing soap on the incidence of possible and probable ventilator-
associated pneumonia (VAP), bloodstream infection (BSI), central-
line  associated  bloodstream  infections  (CLABSI),  urinary  tract
infections  (UTI)  and  catheter-associated  urinary  tract  infections
(CAUTI).
Definitions and methods:
Demographic  characteristics  and  clinical  data  of  patients  will  be
collected using a case report form that was elaborated specifically
for this study (attachment 1) .
Definitions
We will take into consideration only the infections arisen at least 48
hours after the admission to the above mentioned wards.
Sepsis is defined as a systemic inflammatory response syndrome
(SIRS) with a probable and/or confirmed infection [9].
Specifically, VAP, BSI, CABSI, UTI e CAUTI are defined according to
the  National  Healthcare  Safety  Network  –  Centers  for  Diseases
Control and Prevention definitions [10].
Study design
Prospective single-blinded randomized case-control study.
Study population: all patients admitted to the Intensive Care Unit
(ICU) or to the Post-Cardiosurgical Intensive Care Unit (PC-ICU) of
the University Hospital of Perugia will be enrolled.
These  patients  will  be  randomized  in  two  arms  using  a  specific
software. Patients in the first arm (control arm) will undergo the
usual hygiene procedures with standard soap; in the second arm
(treatment arm) patients will be bathed with 4% CHG-containing
soap  (Neoxidina  mani  4%),  at  least  30  ml  according  to  the
manufacturer indications (see the attached data sheet). In particular
the whole body surface – except for the face – will be i) humidified
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with  water  impregnated  washcloths,  ii)  bathed  with  4%  CHG-
impregnated  washcloths  (at  least  30  ml)  and,  after  at  least  30
seconds, iii) rinsed with water-impregnated washcloths.
This product is already in use in our hospital to prepare patients
before a surgical intervention. We will evaluate and compare the
global insidence of sepsis in the two arms and, secondary, incidence
of VAP, BSI, CABSI, UTI and CAUTI.
In addition to this, we will collect demographic data of each patients
and  data  about  comorbidities,  cause  of admission  and  infections
occured during the hospital stay. 
This study is single-blindend. Physicians that have to collect data, to
diagnose infections and to analyse data won’t be directly involved in
washing procedures and they are not member of the medical staff of
ICU and/or TIPOC. Moreover, only nurses that will wash patients by
their own hands will know the arm in which the patient is. Both the
usual  soap  and  the  Neoxidina  mani  4%  (with  chlorhexidine
gloconate 4%) have no colour nor other item than can favour their
identification.
Figure 1: Study design
Patients enrolment.
Inclusion criteria: all patients aged ≥ 18 years old admitted to ICU 
or TIPOC.
Exclusion criteria:
- Age < 18 years old;
- patients with burns;
- patients with known allergy to chlorhexidine and/or one of the 
components of Neoxidina mani 4%;
- patients with toxic epidermal necrolysis o Stevens-Johnson 
syndrome.
- pregnancy
Data will be collected on specific paper form and, then, analyzed
using computerized methods (section “Criteria and data collection
methods”).
Relative risk of the procedure and risk/benefit evaluation. 
Neoxidina  mani  4%  can  rarely  cause  irritation  of  the  exposed
surfaces  especially  after  prolonged  exposure.  To  our  knowledge,
major  adverse  events  due  to  Neoxidina  mani  4%  haven’t  been
described till today.
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Study 
population
Control Arm STANDARD SOAP
Treatment Arm NEOXIDINA MANI 4%
randomisation
 1:1

                                                  
Being  randomised  to  the  treatment  arm  could  have  a  beneficial
effect in term of hospital acquired risk reduction. 
The aim of the present study is to evaluate if 4% CHG daily bathing
in intensive care settings could reduce HAI acquisition rate. As a
consequence,  considering  HAI-associated  morbidity  mortality  and
social costs [1-2], benefits appear to be higher than risks.
Sample Size
Sample size will be between 420 and 1000 patients. Sample size
was calculated after a pre-trial evaluation of HAI. We retrospectively
measured the pre-trial incidence of HAI at ICU and PC-ICU (patients
admitted to ICU and PC-ICU between January, 1st and January, 31st
2015).  Twenty  patients  out  of  66  suffered  from  at  least  1  HAI
(incidence 30.3%).
By adopting an alpha error tolerance (false-positive risk) equal to
0.05, beta error tolerance (false-negative risk) equal to 0.1, power
equal to 0.9, a potential reduction of HAI incidence by 10% and a
percentage  between  5%  and  8%  of  potential  dropouts,  we
calculated that a sample size of at least 410-420 patients would be
required to provide sufficient power to detect significant differences.
According to the Italian Law, patients with altered mentation at the
admission could be directly enrolled by the physician after a clinical
evaluation. At the recovery of consciousness, the patient will receive
the specific paper to provide his consent or not. 
Data analysis
Data  will  be  analysed  with  a  statistical  software.  Distribution  of
variables will be assessed by Kologorov-Smirnov deviation. Normal
variables  will  be  represented  as  mean  +/-  standard  deviation,
continuous non Gaussian variables will be represented as median
and interquartile range, categorical variables will be represented as
frequency  and  percentage.  Comparison  between  groups  will  be
performed with two-tailed t-test, Mann-Whitney test or chi-square
test with Yate’s correction, depensind on variable distribution. Data
analysis will be made by physicians blinded to the study arm.
 
Data collection.
We  will  enrol  420  to  1000  patients  in  up  to  one  year.
Ramdomisation will be done by a specific sofware; it will be a simple
1:1 randomisation at patient-level. To evaluate infections we will
use data from the routine clinical practice; patients in the two arms
will  be  evaluated  in  the  standard  way  and  without  differences
between the two arms.
Data will be collected with an ad hoc clinical report form (CRF); data
about  sex,  age,  demographic  characteristics,  comorbidities  –
evaluated by Charlson comorbidity index – and infections will be
collected in the same above mentioned CRF.
These data will be collected and analysed by physicians blinded to 
the randomisation.
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Patient’s consent 
Patients will be informed about the study protocol by an ad hoc
chart with which they can provide their consent. For unconscious
patients or patients unable to provide their consent, at admission a
physician will decide patients’ enrolment on the basis of their clinical
conditions. These patients will provide their consent as soon as their
regain consciousness. 
Results publications
The findings of the present study will be published- if possible – on 
international medical journals. All the participating physicians will be
citated according to their role in the study. All of them have 
copyright about these data.
Ethical considerations
The present study will be conducted to improve the present clinical
practise and to reduce the risk of infection during the hospital stay.
The proposed strategy appear to be promising to reach the declared
aims and almost adverse event free fot patients. The present study
will be conducted in agreement with the declaration of Helsinki.
References
[1]  Kaye  KS,  Marchaim  D,  Chen  TY,  et  al.  Effect  of  nosocomial  bloodstream
infections on mortality, length of stay and hospital costs in older adults.  J Am
Geriatr Soc. 2014; 62(2): 306-311.
[2]  Roberts  RR,  Scott  RD  II,  Hota  B,  et  al.  Costs  attributable  to  healthcare-
associated infection in hospitalized adults and a comparison of economic methods.
Med Care. 2010; 48(11): 1026-1035.
[3] Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health care infection control
practices advisory committee. 2007 guideline for isolation precautions: preventing
transmission of infectious agents in health care settings. Am J Infect Control. 2007;
35(10)(suppl2): S65-S164.
[4] Boyce JM, Pittet D. Healthcare Infection control practices advisory committee.
Society for healthcare epidemiology of America. Association for professionals in
infection control. Infectious diseases society of America. Hand hygiene task force.
Guideline  for  hand  hygiene  in  health-care  settings:  recommendations  of  the
healthcare  infection  control  practices  advisory  committee  and  the
HICPAC/SHEA/APIC/IDSA han hygiene task force.  Infect Control Hosp Epidemiol,
2002; 23(12)(suppl): S3-S40. 
[5]  Huskins  WC,  Huckabee  CM,  O’Grady  NP,  et  al.  Intervention  to  reduce
transmission of resistant bacteria in intensive care. N Engl J Med. 2011; 364: 1407-
1418.
[6]  Huang  SS,  Septimus  E,  Kleinman  K,  et  al.  Targeted  versus  universal
decolonization to prevent ICU infection. N Engl J Med. 2013; 368: 2255-2265.
[7] Noto MJ, Domenico HJ, Byrne DW, et al. Chlorexidine bathing and health care-
associated infections: a randomized clinical trial. JAMA. 2015; 313(4): 369-378.
[8] Climo MW, Yokoe DS, Warren DK, et al. Effect of daily chlorhexidine bathing on
hospital-acquired infection. N Engl J Med. 2013; 368: 533-542.
[9]  Dellinger  RP,  Levy  MM,  Rhodes  A,  et  al.  Surviving  sepsis  campaign:
international guidelines for management of severe sepsis and septic shock: 2012.
Crit Care Med. 2013; 41(2): 580-637.
[10]  Centers  for  Diseases  Control  and  Prevention.  CDC/NHSN  surveillance
definitions  for  specific  types  of  infections;  http://www.cdc.gov/nhsn.  Accesso  il
27/04/2015.
The principal investigator
Dott. Maurizio Fiorio
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