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) (REDUCE-MRSA)

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

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.

Study Overview

• Status: Completed
• Conditions: Methicillin-resistant Staphylococcus Aureus
• Intervention / Treatment: Drug: Chlorhexidine bath and nasal mupirocin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 74256
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States
      • Alaska Regional
  • California
    • Thousand Oaks, California, United States
      • Los Robles Hosp & Med Ctr
  • Colorado
    • Aurora, Colorado, United States
      • The Medical Center of Aurora
  • Florida
    • Brandenton, Florida, United States
      • Blake Medical Center
    • Brandon, Florida, United States
      • Brandon Hospital
    • Ft. Lauderdale, Florida, United States
      • Columbia Hosp Corp S Broward (Westside)
    • Ft. Lauderdale, Florida, United States
      • Palms West Hospital
    • Ft. Lauderdale, Florida, United States
      • Plantation General
    • Hudson, Florida, United States
      • Regional Med Cr Bayonet Point
    • Largo, Florida, United States
      • Largo Medical Center
    • New Port Richey, Florida, United States
      • Community Hospital
    • Orange Park, Florida, United States
      • Orange Park Med Ctr
    • Port Charlotte, Florida, United States
      • Fawcett Memorial Hospital
    • Sarasota, Florida, United States
      • Doctors Hospital of Sarasota
    • Sun City Center, Florida, United States
      • South Bay Hospital
    • Tallahassee, Florida, United States
      • Capital Regional Med Ctr
  • Georgia
    • Macon, Georgia, United States
      • Coliseum (Macon) Northside
    • Macon, Georgia, United States
      • Coliseum Medical Center
    • Tucker, Georgia, United States
      • Cartersville Medical Center
  • Idaho
    • Idaho Falls, Idaho, United States
      • Eastern Idaho Reg Med Ctr
  • Mississippi
    • Gulfport, Mississippi, United States
      • Garden Park Medical Center
  • Missouri
    • Kansas City, Missouri, United States
      • Lee's Summit Medical Center
    • Kansas City, Missouri, United States
      • Menorah Medical Center
    • Kansas City, Missouri, United States
      • Overland Park Regional Hospital
    • Kansas City, Missouri, United States
      • Research Belton Hospital
  • Nevada
    • Las Vegas, Nevada, United States
      • Moutainview Medical Center
  • New Hampshire
    • Derry, New Hampshire, United States
      • Parkland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Oklahoma University Medical Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States
      • Grand Strand Regional Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States
      • Parkridge Medical Center
    • Nashville, Tennessee, United States
      • Centennial Medical Center
    • Smyrna, Tennessee, United States
      • Stonecrest
  • Texas
    • Austin, Texas, United States
      • St. David's Medical Center
    • El Paso, Texas, United States
      • Del Sol Medical Center
    • El Paso, Texas, United States
      • Las Palmas Medical Center
    • Plano, Texas, United States
      • Medical Center of Plano
    • San Antonio, Texas, United States
      • Methodist Hospital
    • Webster, Texas, United States
      • Clear Lake Regional
  • Virginia
    • Blacksburg, Virginia, United States
      • Montgomery Regional Hospital
    • LowMoor, Virginia, United States
      • Columbia Alleghany Regional Hospital
    • Pulaski, Virginia, United States
      • Pulaski Community Hospital
    • Richmond, Virginia, United States
      • Chippenham Johnston Willis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Arm 1: Usual Care-Active Surveillance; Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
ACTIVE_COMPARATOR: Arm 2: Targeted Decolonization; Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+	Drug: Chlorhexidine bath and nasal mupirocin; 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)
ACTIVE_COMPARATOR: Arm 3: Universal Decolonization; Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Continuation of Contact Precautions for MRSA+	Drug: Chlorhexidine bath and nasal mupirocin; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Harvard Pilgrim Health Care
• Collaborators: Centers for Disease Control and Prevention; University of California, Irvine; Agency for Healthcare Research and Quality (AHRQ); Hospital Corporation of America; Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Healthcare Institute
• Investigators: Principal Investigator: Richard Platt, MD, MS, Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Healthcare Institute; Principal Investigator: Edward Septimus, MD, Hospital Corporation of America (HCA)

Publications and helpful links

General Publications

• Platt R, Takvorian SU, Septimus E, Hickok J, Moody J, Perlin J, Jernigan JA, Kleinman K, Huang SS. Cluster randomized trials in comparative effectiveness research: randomizing hospitals to test methods for prevention of healthcare-associated infections. Med Care. 2010 Jun;48(6 Suppl):S52-7. doi: 10.1097/MLR.0b013e3181dbebcf.
• Huang SS, Septimus E, Platt R. Targeted decolonization to prevent ICU infections. N Engl J Med. 2013 Oct 10;369(15):1470-1. doi: 10.1056/NEJMc1309704. No abstract available.
• Huang SS, Septimus E, Kleinman K, Moody J, Hickok J, Avery TR, Lankiewicz J, Gombosev A, Terpstra L, Hartford F, Hayden MK, Jernigan JA, Weinstein RA, Fraser VJ, Haffenreffer K, Cui E, Kaganov RE, Lolans K, Perlin JB, Platt R; CDC Prevention Epicenters Program; AHRQ DECIDE Network and Healthcare-Associated Infections Program. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013 Jun 13;368(24):2255-65. doi: 10.1056/NEJMoa1207290. Epub 2013 May 29. Erratum In: N Engl J Med. 2013 Aug 8;369(6):587. N Engl J Med. 2014 Feb 27;370(9):886.

Helpful Links

• AHRQ Toolkit: Universal ICU Decolonization: An Enhanced Protocol

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: September 19, 2009
• First Submitted That Met QC Criteria: September 19, 2009
• First Posted (ESTIMATE): September 21, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: MRSA infection
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Disinfectants; Mupirocin; Chlorhexidine
• Other Study ID Numbers: PH000223K; HHSA2902005003I; TO #11