Clinical Trial to Reduce Antibiotic Resistance in European Intensive Cares

Hospital Acquired Infections Clinical Trial

— MOSAR-ICU  

Official title:

Mastering Hospital Antibiotic Resistance, a Cluster Randomized Intervention Study in Intensive Care Units Throughout Europe (Work Package 3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976638
• Other study ID #: LSHP-CT-2007-037941
• Secondary ID: WP3
• Status: Completed
• Phase: N/A
• First received: September 11, 2009
• Last updated: August 3, 2012
• Start date: June 2008
• Est. completion date: May 2011

Study information

• Verified date: August 2012
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: Ethics Committee for Clinical ResearchGreece: Ethics CommitteeLuxembourg: Comite National d'Ethique de RechercheSlovenia: Ethics CommitteeFrance: Institutional Ethical CommitteeSpain: Comité Ético de Investigación ClínicaItaly: Ethics CommitteeLatvia: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14318
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Cross Infection
• Hospital Acquired Infections

Intervention

Other:
• Chromogenic surveillance
All admitted patients are screened on admission for MRSA and VRE by chromogenic agar and isolated when positive
• Molecular surveillance
All patients are screened for MRSA and VRE by PCR; and for ESBL by chromogenic agar on admission. Positive patients are isolated

Locations

Country	Name	City	State
France	Hopital Henri Mondor	Creteil
France	Raymond Poincare Hospital	Garches
France	Hopital Paris Saint Joseph	Paris
Greece	Laikon General Hospital	Athens
Greece	University General Hospital Attikon	Athens
Italy	San Camillo Forlanini Hospital	Rome
Latvia	Paul Stradins University Hospital	Riga
Luxembourg	Centre Hospitalier de Luxembourg	Luxembourg
Portugal	Hospital Geral de Sto Antonio	Porto
Portugal	Tras-os-Montes e Alto Douro	Vila Real
Slovenia	University Clinic of Respiratory and Allergic Diseases	Golnik
Slovenia	University Medical Center Ljubljana	Ljubljana
Spain	Hospital Clinic Y Provencal	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
UMC Utrecht

Countries where clinical trial is conducted

France,  Greece,  Italy,  Latvia,  Luxembourg,  Portugal,  Slovenia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Colonization with MRSA, VRE and ESBL	By taking surveillance swabs from nose, perineum and wounds (if present) on admission we will assess whether patients are colonized with MRSA, VRE and ESBL at the moment of ICU admission. Swabs will be processed on chromogenic agars.	On admission	No
Primary	Colonization with MRSA, VRE and ESBL	By taking surveillance swabs twice weekly from nose, perineum and wounds (if present) we will assess whether patients become colonized with MRSA, VRE and ESBL during ICU stay. Swabs will be processed on chromogenic agars.; Note: for patients admitted for longer than 21 days, surveillance is reduced to once weekly.	During ICU stay	No
Secondary	Incidence density of new acquisitions with MRSA, VRE and ESBL individually.	In phase 2, we implement a hygiene improvement program. We will assess if this program reduces the number of patients acquiring colonization with MRSA, VRE and ESBL. We will measure colonization as stated in the primary outcome measure.; In phase 3, we will implement direct feedback of screening results, and isolation of colonized patients. Swabs will be processed either by chromogenic agar (a) or molecular tests (b). Thus, the effect of these interventions on incidence density of new acquisitions of MRSA, VRE or ESBL will be assessed.	Acquired during ICU stay (median LOS 14 days)	No
Secondary	ICU-acquired bacteremia rates with MRSA,VRE or ESBL.	We will collect data on all bacteremias occuring during ICU stay, after completion of the trial. We include all bacteremias with s aureus (MSSA and MRSA), e faecium/ e faecalis ("S" and "R") and enterobacteriaceae ("S" and "R"). Data will be collected from the microbiology labs.	Acquired during ICU stay (median LOS 14 days)	No
Secondary	28 day-mortality	We will collect length of stay, and disposition at d28 as well as disposition at discharge from the ICU. Data will be collected in the online CRF.	28 days	No