Clinical trial NCT00976638: Clinical Trial to Reduce Antibiotic Resistance in European Intensive Cares
Official title: Mastering Hospital Antibiotic Resistance, a Cluster Randomized Intervention Study in Intensive Care Units Throughout Europe (Work Package 3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hospital Acquired Infections
Keywords: Antimicrobial Resistant Bacteria
Hospital acquired infections
Colonization
Bacteremia
MRSA
VRE
ESBL
Intensive Care
ICU
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2009-09-14
Enrollment: 14318
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Colonization of patients with Antimicrobial Resistant Bacteria (AMRB) like Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin-Resistant Enterococcus (VRE) and Extended-Spectrum Beta-Lactamases (ESBL) enterobacteriaceae leads to infections; and ultimately to adverse outcomes (eg prolonged hospital stay, death). This is an urgent problem in Europe, especially in Intensive Care Units (ICUs).

In this trial, colonization of patients with these AMRB will be assessed in the baseline period (6m). In phase 2 the effect of a Hygiene Improvement Program, including Chlorhexidine body washings and a Hand Hygiene training program, will be assessed (6m). In phase 3 units will be randomized to either Active Surveillance with Chromagar based tests or a Molecular based tests.

Study Hypothesis: the abovementioned interventions will reduce ICU-acquired colonization rates with MRSA, VRE and ESBL.

Detailed description: A cluster-randomized trial with a stepped wedge design will be conducted in adult ICU's throughout Europe

The MOSAR-ICU trial is motivated by three primary considerations:

1. Advances in behavioral sciences and research about (hand) hygiene compliance have allowed a better understanding of barriers to increase compliance with (hand) hygiene practices within healthcare institutions;
2. Recent investigations have identified new rapid tests, both chromogenic media and molecular based tests, which may help identifying previously unknown carriage of AMRB at the time of admission; and
3. Currently practiced procedures, such as regular surveillance of all patients and daily cleansing of ICU patients with Chlorhexidine, have not been evaluated properly for their effectiveness.

In conclusion, evidence base derived recommendations from prospective studies regarding the costeffectiveness of different control strategies are lacking.

This study assess the impact of the three interventions on ICU acquired colonisation rates for AMRB(MRSA,VRE and ESBL).

Study design: Multi-center, cluster-randomised clinical trial.

Study population: Adult patients admitted to the ICU.

Intervention: The first phase of the study will be a 6-month baseline period to determine acquisition rates of AMRB during current standard practice in the individual participating centers (including currently performed surveillance strategies). The second phase will consist of a Hygiene Improvement Program to improve standard precautions and hand hygiene; and daily washing of all ICU patients with Chlorhexidine gluconate (HIP; 6 months). In both periods Contact Precautions (contact isolation) will be implemented for carriers of AMRB, as identified upon clinical cultures and following current practice of individual wards. In the third phase of the study (12 months) units will be randomized, and all interventions of phase 2 will be continued in all units. Half of the units will implement surveillance (admission and twice weekly cultures) of all admitted patients for carriage of MRSA and VRE using chromogenic agar. The other half will add molecular based rapid testing of ALL admission cultures for MRSA and VRE in addition to twice weekly screening of all patients with Chromagar based tests for MRSA, VRE and ESBL.

Main study endpoints: ICU-acquired colonization rates with MRSA, VRE and ESBL.

Primary Objective: To evaluate the impact of enhanced standard barrier precautions and rapid screening with targeted isolation of patients carrying AMRB on transmission of AMRB.

Secondary Objectives:

* Evaluate the impact of interventions on ICU-acquired bacteremia rates with MRSA, VRE or ESBL.
* Evaluate the impact of the HIP intervention on frequency and quality of hand hygiene, the application of standard precautions and the use of contact precautions during patient care.
* Evaluate the effect of the three strategies on other patient outcomes, including length of stay and in hospital mortality.
* Evaluate the overall antibiotic use and effectiveness of empirical treatment of ICU-acquired bacteremia.
* Evaluate the effect of the three strategies on the incidence density of new acquisitions with MRSA, VRE and ESBL individually.

Eligibility criteria: Inclusion Criteria:

* colonization with either MRSA, VRE or ESBL is endemic
* at least one dedicated infection control physician
* ability to obtain, store and analyze surveillance cultures
* at least 8 ICU beds; all of which have possibility for mechanical ventilation
* ability to collect the data required for analysis
* written approval of the institution's IRB
* signed protocol signature page

Exclusion Criteria:

* burn units
* cardiothoracic units
* pediatric and neonatal ICUs
* ICU is currently using rapid diagnostic testing in their screening program for AMRB
* ICU is planning to enroll subjects in studies testing investigational agents for the purpose of eradicating or preventing colonization with MRSA, VRE or ESBL or devices or practice management strategies that have colonization and/or infection with AMRB as an outcome
* using SOD/ SDD or any topical antimicrobial therapy
* using chlorhexidine body washings

Primary outcomes:
measure: Colonization with MRSA, VRE and ESBL
timeFrame: On admission
measure: Colonization with MRSA, VRE and ESBL
timeFrame: During ICU stay
Secondary outcomes:
measure: Incidence density of new acquisitions with MRSA, VRE and ESBL individually.
timeFrame: Acquired during ICU stay (median LOS 14 days)
measure: ICU-acquired bacteremia rates with MRSA,VRE or ESBL.
timeFrame: Acquired during ICU stay (median LOS 14 days)
measure: 28 day-mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Garches
country: France
facility: Raymond Poincare Hospital
city: Paris
country: France
facility: Hopital Paris Saint Joseph
city: Athens
country: Greece
facility: Laikon General Hospital
city: Athens
country: Greece
facility: University General Hospital Attikon
city: Rome
country: Italy
facility: San Camillo Forlanini Hospital
city: Riga
country: Latvia
facility: Paul Stradins University Hospital
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
city: Porto
country: Portugal
facility: Hospital Geral de Sto Antonio
city: Vila Real
country: Portugal
facility: Tras-os-Montes e Alto Douro
city: Golnik
country: Slovenia
facility: University Clinic of Respiratory and Allergic Diseases
city: Ljubljana
country: Slovenia
facility: University Medical Center Ljubljana
city: Barcelona
country: Spain
facility: Hospital Clinic Y Provencal
Study officials:
affiliation: UMC Utrecht
name: Marc Bonten, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Derde LPG, Cooper BS, Goossens H, Malhotra-Kumar S, Willems RJL, Gniadkowski M, Hryniewicz W, Empel J, Dautzenberg MJD, Annane D, Aragao I, Chalfine A, Dumpis U, Esteves F, Giamarellou H, Muzlovic I, Nardi G, Petrikkos GL, Tomic V, Marti AT, Stammet P, Brun-Buisson C, Bonten MJM; MOSAR WP3 Study Team. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis. 2014 Jan;14(1):31-39. doi: 10.1016/S1473-3099(13)70295-0. Epub 2013 Oct 23.