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)

• ClinicalTrials.gov Identifier: NCT00980980
• Recruitment Status: Completed
• First Posted: September 21, 2009
• Results First Posted: July 30, 2014
• Last Update Posted: May 2, 2017
• Sponsor: Harvard Pilgrim Health Care
• Collaborators: Agency for Healthcare Research and Quality (AHRQ); Centers for Disease Control and Prevention; Hospital Corporation of America; University of California, Irvine; Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Healthcare Institute
• Information provided by (Responsible Party): Richard Platt, Harvard Pilgrim Health Care

Tracking Information

• First Submitted Date: September 19, 2009
• First Posted Date: September 21, 2009
• Results First Submitted Date: May 14, 2014
• Results First Posted Date: July 30, 2014
• Last Update Posted Date: May 2, 2017
• Study Start Date: September 2009
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2014)

Main Outcome: Patients With Nosocomial MRSA Clinical Cultures [ Time Frame: 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. ]

Hazard ratio for ICU-attributable MRSA+ clinical cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.

• Original Primary Outcome Measures (submitted: September 19, 2009): Main Outcome: Patients with Nosocomial MRSA Clinical Cultures

Current Secondary Outcome Measures (submitted: March 22, 2017)

• MRSA Bloodstream Infection [ Time Frame: 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. ]
  Hazard ratio for ICU-attributable MRSA+ blood cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
• ICU-attributable All-pathogen Bloodstream Infection [ Time Frame: 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. ]
  Hazard ratio for ICU-attributable positive blood culture from any pathogen, comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
• Intervention Impact on Healthcare Costs [ Time Frame: 12-month period ]
  Costs (in dollars) per 1000 ICU-admissions associated with 3 ICU strategies to reduce ICU Bloodstream infection (BSI), (Arms 1-3).
• Blood Culture Contamination Rates [ Time Frame: 24-month time frame for this analysis represents a 6-month baseline and 18-month intervention period. ]
  Odds ratio for ICU-attributable blood culture contamination rates, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital.
• Intervention Impact on Bacteriuria and Candiduria [ Time Frame: 30-month time frame represents 12-month baseline and 18-month intervention periods. ]
  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.
• Intervention Impact on Mupirocin Susceptibility of MRSA Isolates [ Time Frame: 25-month time frame represents 7-month baseline and 18-month intervention periods ]
  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.
• Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates [ Time Frame: 25-month time frame represents 7-month baseline and 18-month intervention periods ]
  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.

Original Secondary Outcome Measures (submitted: September 19, 2009)

• Nosocomial MRSA Bloodstream and Urinary Cultures
• Routinely reported central line associated blood stream infections (CLABSI).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: Cluster Randomized Trial of Hospitals to Assess Impact of Targeted Versus Universal

Brief Summary

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

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Primary Purpose: Prevention
• Condition: Methicillin-resistant Staphylococcus Aureus

Intervention

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)

Study Arms

• 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+
  Intervention: Drug: Chlorhexidine bath and nasal mupirocin
• Active Comparator: Arm 3: Universal Decolonization
  Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Continuation of Contact Precautions for MRSA+
  Intervention: Drug: Chlorhexidine bath and nasal mupirocin

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2014): 74256
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 2011
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00980980
• Other Study ID Numbers: PH000223K; HHSA2902005003I; TO #11
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Richard Platt, Harvard Pilgrim Health Care
• Original Responsible Party: Richard Platt, MD MS, Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Healthcare Institute
• Current Study Sponsor: Harvard Pilgrim Health Care
• Original Study Sponsor: Same as current

Collaborators

• Agency for Healthcare Research and Quality (AHRQ)
• Centers for Disease Control and Prevention
• Hospital Corporation of America
• University of California, Irvine
• 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)
• Principal Investigator: Susan Huang, MD MPH; University of California, Irvine

• PRS Account: Harvard Pilgrim Health Care
• Verification Date: March 2017