Clinical Trial to Reduce Antibiotic Resistance in European Intensive Cares (MOSAR-ICU)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MJM Bonten, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00976638
First received: September 11, 2009
Last updated: August 3, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention
Hospital Acquired Infections
Other: Chromogenic surveillance
Other: Molecular surveillance

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Mastering Hospital Antibiotic Resistance, a Cluster Randomized Intervention Study in Intensive Care Units Throughout Europe (Work Package 3)

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Colonization with MRSA, VRE and ESBL [ Time Frame: On admission ] [ Designated as safety issue: No ]
    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.

  • Colonization with MRSA, VRE and ESBL [ Time Frame: During ICU stay ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Incidence density of new acquisitions with MRSA, VRE and ESBL individually. [ Time Frame: Acquired during ICU stay (median LOS 14 days) ] [ Designated as safety issue: No ]

    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.


  • ICU-acquired bacteremia rates with MRSA,VRE or ESBL. [ Time Frame: Acquired during ICU stay (median LOS 14 days) ] [ Designated as safety issue: No ]
    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.

  • 28 day-mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 14318
Study Start Date: June 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chromogenic Arm
Active surveillance of colonization with MRSA or VRE by chromogenic agar with isolation of positive patients.
Other: Chromogenic surveillance
All admitted patients are screened on admission for MRSA and VRE by chromogenic agar and isolated when positive
Other Name: chromogenic screening
Active Comparator: Molecular Arm
Active surveillance of colonization with MRSA and VRE by PCR; and of ESBL by chromogenic agar with isolation of positive patients
Other: Molecular surveillance
All patients are screened for MRSA and VRE by PCR; and for ESBL by chromogenic agar on admission. Positive patients are isolated
Other Name: molecular screening

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976638

Locations
France
Hopital Henri Mondor
Creteil, France, 94000
Raymond Poincare Hospital
Garches, France, F-92380
Hopital Paris Saint Joseph
Paris, France, 75674
Greece
Laikon General Hospital
Athens, Greece, 11527
University General Hospital Attikon
Athens, Greece, 12462
Italy
San Camillo Forlanini Hospital
Rome, Italy, 00152
Latvia
Paul Stradins University Hospital
Riga, Latvia, LV-1008
Luxembourg
Centre Hospitalier de Luxembourg
Luxembourg, Luxembourg, L-1210
Portugal
Hospital Geral de Sto Antonio
Porto, Portugal, 4260-363
Tras-os-Montes e Alto Douro
Vila Real, Portugal, 5000-508
Slovenia
University Clinic of Respiratory and Allergic Diseases
Golnik, Slovenia, 4204
University Medical Center Ljubljana
Ljubljana, Slovenia, SI 1000
Spain
Hospital Clinic Y Provencal
Barcelona, Spain, 8025
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: Marc Bonten, Prof, MD UMC Utrecht
  More Information

No publications provided by UMC Utrecht

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MJM Bonten, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00976638     History of Changes
Other Study ID Numbers: LSHP-CT-2007-037941, WP3
Study First Received: September 11, 2009
Last Updated: August 3, 2012
Health Authority: Portugal: Ethics Committee for Clinical Research
Greece: Ethics Committee
Luxembourg: Comite National d'Ethique de Recherche
Slovenia: Ethics Committee
France: Institutional Ethical Committee
Spain: Comité Ético de Investigación Clínica
Italy: Ethics Committee
Latvia: Institutional Review Board

Keywords provided by UMC Utrecht:
Antimicrobial Resistant Bacteria
Hospital acquired infections
Colonization
Bacteremia
MRSA
VRE
ESBL
Intensive Care
ICU

Additional relevant MeSH terms:
Cross Infection
Infection
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on July 31, 2014