Cluster Randomized Trial of Hospitals to Assess Impact of Targeted Versus Universal Strategies to Reduce Methicillin-resistant Staphylococcus Aureus (MRSA) in Intensive Care Units (ICUs)

Study Overview
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Brief Summary
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The Randomized Evaluation of Decolonization versus Universal Clearance to Eliminate MRSA (REDUCE MRSA) Trial is a cluster randomized trial of the comparative effectiveness of three strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units. The three strategies to be evaluated are: screening on admission followed by isolation of MRSA+ patients screening on admission followed by isolation and decolonization of MRSA+ patients universal decolonization on admission with no screening. The decolonization regimen involves bathing with chlorhexidine plus intra-nasal application of mupirocin. The main outcome will be MRSA+ clinical cultures. The study is a partnership between the CDC, the CDC Prevention Epicenters, and the Hospital Corporation of America.

Detailed Description
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Baseline data involving 12 months of data for participating hospitals (July 2008 - June 2009) was collected prior to randomization to account for size and ICU baseline prevalence of MRSA in randomization scheme. Randomization occurred at the hospital level. Eligibility survey was conducted to determine exclusion criteria. As of May 2010, enrollment has been closed. 45 hospitals were randomized, but two were found to meet exclusion criteria and were excluded. As-randomized (or as-assigned) analysis included 43 hospitals, representing 74 ICUs. Individual (patient-level) subject enrollment during intervention is 74,256.

Official Title
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Cluster Randomized Trial of Hospitals to Assess Impact of Targeted Versus Universal

Conditions
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Methicillin-resistant Staphylococcus Aureus

Intervention / Treatment
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* Drug: Chlorhexidine bath and nasal mupirocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria will include all HCA hospitals that reside in US states where physicians do NOT routinely prescribe decolonization for MRSA + ICU patients. Exclusion Criteria: Exclusion criteria will include hospitals where ICU physicians often prescribe decolonization for MRSA+ ICU patients. Dedicated burn ICUs will also be excluded due to the inability to perform routine bathing. Finally, since the intent is to assess the intervention in adult ICUs, pediatric hospitals will be excluded although patients <13 years old that are admitted to participating adult ICUs will be included in the unit-based intervention.

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm 1: Usual Care-Active Surveillance<br>Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+ | |
| Active Comparator: Arm 2: Targeted Decolonization<br>Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+ | Drug: Chlorhexidine bath and nasal mupirocin<br>* The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US - a combination of daily baths with 2% chlorhexidine cloths , plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily)<br>|
| Active Comparator: Arm 3: Universal Decolonization<br>Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Continuation of Contact Precautions for MRSA+ | Drug: Chlorhexidine bath and nasal mupirocin<br>* The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US - a combination of daily baths with 2% chlorhexidine cloths , plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Outcome: Patients With Nosocomial MRSA Clinical Cultures | Hazard ratio for ICU-attributable MRSA+ clinical cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRSA Bloodstream Infection | Hazard ratio for ICU-attributable MRSA+ blood cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | 
| ICU-attributable All-pathogen Bloodstream Infection | Hazard ratio for ICU-attributable positive blood culture from any pathogen, comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | 
| Intervention Impact on Healthcare Costs | Costs (in dollars) per 1000 ICU-admissions associated with 3 ICU strategies to reduce ICU Bloodstream infection (BSI), (Arms 1-3). | 12-month period | 
| Blood Culture Contamination Rates | Odds ratio for ICU-attributable blood culture contamination rates, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital. | 24-month time frame for this analysis represents a 6-month baseline and 18-month intervention period. | 
| Intervention Impact on Bacteriuria and Candiduria | Proportional hazard ratio for as-randomized, unadjusted, ICU-attributable bacteriuria, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital. High-level bacteriuria is defined as ≥50,000 CFU/mL, high-level candiduria is defined as ≥50,000 CFU/mL. | 30-month time frame represents 12-month baseline and 18-month intervention periods. | 
| Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Odds ratio for MRSA+ isolates from ICU patients expressing low-level mupirocin resistance (LLMR) and high-level mupirocin resistance (HLMR), comparing baseline to intervention period across arms, accounting for clustering by hospital. | 25-month time frame represents 7-month baseline and 18-month intervention periods | 
| Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates | Frequency of MRSA+ isolates from ICU patients with reduced susceptibility to chlorhexidine (CHG) (MIC >4 μg/ml), comparing baseline to intervention period across arms, accounting for clustering by hospital. | 25-month time frame represents 7-month baseline and 18-month intervention periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRSA infection