Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05973916 |
| Other study ID # |
172-22-ASF |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 3, 2023 |
| Est. completion date |
August 3, 2025 |
Study information
| Verified date |
July 2023 |
| Source |
Assaf-Harofeh Medical Center |
| Contact |
Dror Marchaim, MD |
| Phone |
+97289778146 |
| Email |
drormarchaim[@]shamir.gov.il |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A comprehensive intervention to improve the level of cleaning and disinfection of patients'
units, in order to reduce new acquisitions and environmental contamination by multidrug
resistant organisms: a prospective controlled crossover trial, using VYV led lights and
continuous air filtering of patients' rooms, coupled with establishment of a "patient's unit
commando" cleaning team.
Description:
Background and introduction
As declared by the World Health Organization (WHO) in 2016, antimicrobial resistance among
the commonest human pathogens, i.e., the multidrug resistant organisms (MDRO), pose one of
the biggest challenges in modern Medicine and one of the biggest threats to humanity. MDROs
are prevalent in acute-care hospitals, and in addition are continuously emerging at
non-acute-care healthcare settings, and even in the community. The current global SARS-CoV-2
pandemic, further amplifies the enormous burdens imposed by MDROs on hospitalized previously
non-sick individuals. The commonest Gram-positive MDROs are methicillin-resistant
Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridioides
difficile (C. diff). The commonest Gram-negative MDROs are carbapenem-resistant and/or
carbapenemase-producing Enterobacterales (CRE), Acinetobacter baumannii (CRAB), and
Pseudomonas aeruginosa (CRPA). Acquisition of an MDRO in the hospital is associated with
devastating outcomes to the individual patient and with enormous fiscal burden imposed on
health facilities. Moreover, In Israel and in many other countries, there are mandatory
reporting regulations for certain MDROs, and the rates of MDRO acquisitions serve as "pay per
performance" initiatives. This adds additional burden in terms of potential bad reputation
and reductions in reimbursements.
The patient's immediate environment, specifically "high-touch surfaces" (e.g., touch screens,
monitor, respirator, feeding device, infusion pump, the entire bed, cabin, nurse's call-on
button, light switches, fluid balance charts hanged on bed, linen, armchairs, curtains, and
so on), serves as reservoir and vector for MDRO distribution and transmission from patient to
patient. Therefore, health facilities have strong motivation to improve the level of cleaning
and disinfection of patients' immediate environment, in an effort to improve patient safety,
quality of clinical care, and reduce hospital costs while improving its reputation.
Many items commonly used in traditional and routine care of hospitalized patients, have been
described as reservoirs and/or fomites for transmission of pathogens, which can lead to
nosocomial MDRO-related outbreaks. Environmental remnants of MDROs on immediate high touch
surfaces spread from patient to patient through staff, shared equipment, or directly from
patient to patient (less common). While a carrier of a specific MDRO reside in his/her room
or unit, the same MDRO can be isolated (frequently in high inoculums) from the patient's
immediate environment (e.g. bedrail, monitor, infusion pump), from high-touch surfaces (e.g.,
light switches, water taps, nurse's call-on button), and even from distant locations in the
room (e.g. ceiling). MDROs can remain viable and survive in those transmitting-prone
environmental locations for prolonged periods, long after the previous carrier who
contaminated the environment had been discharged.
The levels of environmental cleaning and disinfection of high-touch surfaces, is known to be
low in hospitals. The current cleaning guidelines at Shamir Medical Center (SMC), as per the
Israeli MOH regulations, are as follows: while the patient is in their bed, the unit is
subjected to daily cleaning, and after the patient leaves, the unit is subjected to "terminal
cleaning", a supposable standardized enhanced cleaning protocol. Recurrent audits and
observations from all over the world clearly suggests that the level of cleaning and
disinfection of patients' environments in acute-care hospitals is unsatisfactory most hours
of the day. In order to improve this crucial aspect associated with MDRO transmission and
spread in hospitals, a multidisciplinary approach is warranted, with implementation of novel
solutions both technological, and with regards to aspects associated with human capital. To
add an additional complexity to the situation, in Israeli hospitals, as in many other
countries, the responsibility of cleaning/disinfecting patient's immediate environment, is
divided. The bed, bedside table, infusion pump, monitor, cables and additional immediate
surroundings of an individual patient, are cleaned by nurse assistants, while the floor,
sink, toilets, light switches and walls (shared by all room occupants), are cleaned by
environmental services (EVS) personnel. This separation in responsibilities creates eventual
gaps in the overall level of cleaning/disinfection of certain items, which are frequently
associated with MDRO transmission. There are continuous shortages both in terms of full time
effort (fte) allocation, and in terms of specified professional training, among these two
frequently neglected sectors (i.e., nurse assistants and EVS personnel). The employment
turnaround time of these personnel sectors is very high, with no establishment of a stable
local base of knowledge and expertise. In order for an intervention that improves the level
of cleaning /disinfection of patients' environment to be successful, human capital
considerations must be acknowledged and addressed. A designated team (referred to as
"cleaning commando" in certain facilities), responsible to all the various aspects associated
with cleaning and disinfecting the patient's environment, but have no other additional
responsibilities, and is managed by the same management, could theoretically improve the
human capital aspects associated with improving the level of cleaning/disinfecting patients'
environments in hospitals.
The market is flooded in recent years, and even more since the emergence of the SARS-CoV-2
pandemia, with novel technologies that aim to improve the level of environmental disinfection
of patients' surroundings and high-touch surfaces. These technologies should always be
applied on top of an effective process of cleaning, which is always executed by humans. These
technologies only add an additional level of mechanized controlled process for enhancing
environmental disinfection, but could never replace the necessity of an established effective
and monitored process of initial cleaning, a process that should be executed, as mentioned
above, by trained and centrally managed personnel. Initially, many of the technologies in
this field of immediate environment disinfection, were applied on empty patients' units only.
This creates many operational complexities in busy acute-care hospitals, with fast turnaround
time of hospitalized beds. The "new generation" of technologies, are aimed to disinfect
patients' immediate environment, continuously, while the patients reside in the unit. On the
one hand, technology needs to be effective and bactericidal, but on the other hand,
concentrations of the active disinfecting ingredients or materials, should not be toxic and
endanger patients under no circumstances. Continuously disinfecting surfaces by using VYV led
lights, and filtering the air by using the QleanAir Scandinavia® device, are both licensed to
operate while the patients are in the room. Both are "effective" in-vitro against the six
groups of MDROs mentioned above. This could theoretically add an additional mode for
prevention of MDRO transmission and spread in hospitals. However, controlled clinical data,
with 'real' clinical outcomes, pertaining to the actual efficacy of these technologies in
preventing MDRO acquisitions, are absent. In order to convince stakeholder administrators to
invest in implementation of certain preventing technologies, clinical studies, analyzing the
effectiveness of technologies in preventing actual clinical outcomes, are warranted.
Crossover design is considered today the gold standard methodology in the clinical research
field of infection control and hospital epidemiology. This design enables to control for
multiple confounders, associated with the Hawthorne effect, which is very common in studies
assessing the controlled efficacy of a certain infection control newly implemented
intervention.
In order to reduce the environmental contamination by MDRO carriers, and the incidence of
MDRO acquisitions in hospitals by naïve patients, we aim to implement a comprehensive and
multifactorial intervention, to improve the level of cleaning/disinfecting patients'
immediate environment. The suggested intervention will contain components associated with
human capital and with the implementation of two advanced technologies. We aim to trial this
comprehensive intervention, in a prospective crossover design, in a 'real-world' clinical
scenario, analyzing its efficacy on 'hard' and direct clinical outcomes.
Study hypotheses
1. A comprehensive intervention (consisting of establishing a "patient's unit commando"
team, while continuously disinfecting patient's unit by using VYV led lights and
QleanAir Scandinavia® air filtering device) will reduce the rate of new carriage
acquisitions of the MDROs: 1) MRSA, 2) VRE, 3) CRE, 4) A. baumannii, 5) P. aeruginosa,
and 6) C. difficile.
2. A comprehensive intervention (consisting of establishing a "patient's unit commando"
team, while continuously disinfecting patient's unit by using VYV led lights and
QleanAir Scandinavia® air filtering device) will reduce the incidence of
hospital-acquired bloodstream infections (HA-BSI).
3. A comprehensive intervention (consisting of establishing a "patient's unit commando"
team, while continuously disinfecting patient's unit by using VYV led lights and
QleanAir Scandinavia® air filtering device) will reduce the incidence of
hospital-acquired urinary-tract infections (HAUTI).
Study Aim
1. Analyze the role of a comprehensive intervention (consisting of establishing a
"patient's unit commando" team, while continuously disinfecting patient's unit by
using VYV led lights and QleanAir Scandinavia® air filtering device) in reducing
the rate of new carriage acquisitions of MDROs (MRSA, VRE, CRE, A. baumannii, P.
aeruginosa, C. difficile).
2. Analyze the role of a comprehensive intervention (consisting of establishing a
"patient's unit commando" team, while continuously disinfecting patient's unit by
using VYV led lights and QleanAir Scandinavia® air filtering device) in reducing
the incidence of HA-BSI.
3. Analyze the role of a comprehensive intervention (consisting of establishing a
"patient's unit commando" team, while continuously disinfecting patient's unit by
using VYV led lights and QleanAir Scandinavia® air filtering device) in reducing
the incidence of HAUTI.
Study protocol
1. Prospective cluster-randomized placebo-controlled cross-over study design.
2. The study will be conducted over 15 months; each study phase will last 6
months, with a pre-study period (1 month), a washout period (1 month) and a
post study period (1 month).
• Pre-study period: all patient rooms at both departments will be cleaned and
disinfected according to the "common practice" as detailed below.
• Phase I:
o Medicine A: cleaning of patients' rooms will be subjected to a comprehensive
intervention, consisting of: 1) a "patient's unit commando" team for daily and
for terminal cleaning, 2) all lights in patients' room are VYV led lights, and
3) in each room, a QleanAir Scandinavia® filtering machine will be placed.
- Medicine B: patients' rooms will be cleaned and disinfected according to
the current "common practice" as detailed below.
• Washout period in both hospitals: all patient rooms at both departments
will be cleaned and disinfected according to the "common practice" as
detailed below.
• Phase II:
- Medicine A: patients' rooms will be cleaned and disinfected according to
the current "common practice" as detailed below.
- Medicine B: cleaning of patients' rooms will be subjected to a
comprehensive intervention, consisting of: 1) a "patient's unit commando"
team for daily and for terminal cleaning, 2) all lights in patients' room
are VYV led lights, and 3) in each room, a QleanAir Scandinavia®
filtering machine will be placed.
- Post-study period: all patient rooms at both departments will be
cleaned and disinfected according to the "common practice" as
detailed below.
- The "patient's unit commando" team will consist of 6 staff members,
trained specifically by the infection control team at Shamir Medical
Center. The "patient's unit commando" team will be responsible,
during the intervention, for the daily cleaning of the patients
subjected to isolation precautions, and will be conducting the
terminal cleaning following discharge of every patient from the unit
that is under the intervention.
Microbiological studies:
• Clinical cultures are all processed at the SMC clinical microbiology
laboratory. The laboratory adhere to the U.S. Clinical Laboratory Standards
Institute (CLSI) standards and criteria. No additional cultures will be
obtained specifically for this protocol.
o MRSA, VRE, A. baumannii, and P. aeruginosa will be determined according to a
Vitek-2 automated system and according to CLSI breakpoints and criteria.
o CRE will be determined according to the Israeli MOH national diagnostic
guidelines (2013) and based, again, on CLSI criteria.
o Toxin-producing C. difficile will be determined based of a GDH-based
serology test (C. DIFF QUIK CHEK COMPLETE®; Alere™) and if necessary (i.e.,
inconclusive serology test result: positive for C. difficile GDH antigen but
negative for C. difficile toxins), will be confirmed by a PCR-based test
(Xpert® C. difficile; Cepheid©). Samples will be processed according to
national Israeli guidelines (2013) and according to CLSI criteria.
o All MDROs will be stored in -800C for future molecular analyses.
• Representative MDROs will be typed later on for future detailed transmission
dynamics investigations.
- The laboratory will be blinded to the source of the cultures (i.e., to
the fact of whether or not the unit is at its interventional phase).
Patients:
1. The two departments will perform, per local Infection Control regulations: i. Nasal
culture for MRSA upon admission to the unit and weekly thereafter (same day and shift every
week).
ii. Rectal culture for VRE, and CRE upon admission to the unit and weekly thereafter (same
day and shift every week).
iii. Sputum and skin cultures (using sponges) for the presence of A. baumannii and P.
aeruginosa upon admission to the unit and weekly thereafter (same day and shift every week).
2. All the surveillance for MDRO new acquisitions and hospital-acquired bloodstream
infections (BSI) are conducted routinely and continuously by the Infection Control team at
SMC. The PI serves as the head of the Infection Control unit and is personally involved in
the surveillances processes for those endpoints.
3. Acquisitions of pre-specified MDROs:
1. MDRO acquisition will be defined based on clinical samples obtained from
previously-not-known carriers. In addition, surveillance cultures for all the MDRO of
interest (except C. difficile) would be obtained upon admission and weekly thereafter.
An acquisition will be defined as a patient who was negative upon admission but became
positive ≥ 72 hours after admission or within 72 hours after admission if the patient
was hospitalized in the hospital during the last 30 days.
2. MRSA, VRE, and P. aeruginosa will be determined according to the Vitek-2 automated
system and according to Clinical and Laboratory Standards Institute (CLSI) criteria.
3. CRE will be determined according to the Israeli ministry of health (MOH) national
diagnostic guidelines (2013) and based, again, of the CLSI cutoffs and criteria.
4. C. difficile infection will be determined according to the Israeli ministry of health
(MOH) national guidelines (2012), based on the presence of toxin-producing organism:
first by GDH-based serology test and if needed, by confirmatory PCR-based test.
5. The monitoring and surveillance of hospital-acquired BSI, conducted by Infection Control
personnel, is based on the Israeli Ministry of Health monitoring criteria, which
resembles exactly the U.S. Centers for disease Control and Prevention (CDC) criteria.
6. The monitoring and surveillance of hospital-acquired UTI, conducted by Infection Control
personnel, is based on the Israeli Ministry of Health monitoring criteria from 2014,
which resembles (but is not exactly the same) as the U.S. CDC diagnostic criteria.
Power calculations
The power calculations are based on the primary study outcome, which is the MDRO new
acquisitions incidence. Based on surveillance data from SMC, during 2019, the incidence (in
the two departments) of MDRO new acquisition was 4.1 per 1,000 patient days. Even if the
impact of the intervention would be relatively mild, and it will reduce the acquisition rate
by only 10%, the sample size will still enable us with β=0.8 and α=0.01 to determine the
statistical significant efficacy of the intervention.
Statistical analysis
Data will be summarized with descripted statistic based on the Data reference sheet.
The two groups (department ) will be compared for admission data, baseline characteristics
and risk factors with the independent t-test and the Chi-Square test. . New carriage
acquisitions of MDROs (MRSA, VRE, CRE, A. baumannii, P. aeruginosa, C. difficile), the
incidence of HA-BSI and incidence of HAUTI will point estimated by rates, followed by 95%
confidence interval.
Each department will be test for difference between the control and treatment period by the
McNemar test for paired proportions.
Comparisons between study groups will be made by Z test for proportions for each Phase
separately and for the entire study.
