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)

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00980980
First received: September 19, 2009
Last updated: August 18, 2014
Last verified: August 2014
Results First Received: May 14, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Primary Purpose: Prevention
Condition: Methicillin-resistant Staphylococcus Aureus
Intervention: Drug: Chlorhexidine bath and nasal mupirocin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
45 out of 165 Hospital Corporation of America (HCA) hospitals were recruited for this trial of adult ICUs. There was a 12-month baseline period from January 1 through December 31, 2009; a phase-in period from January 1 through April 7, 2010; and an 18-month intervention period from April 8, 2010 through September 30, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
74,256 patients were involved in the intervention period among adult ICUs from the 43 participating hospitals. Routinely collected information for about 48,390 individuals cared for during the baseline period was used for comparison to the experience of the patients in all three arms of the Intervention period.

Reporting Groups
  Description
Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
Arm 2: Targeted Decolonization

Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+

Chlorhexidine bath and nasal mupirocin: The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US – a combination of baths with 2% chlorhexidine cloths plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily)

Arm 3: Universal Decolonization

Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance , Contact Precautions for MRSA+

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)


Participant Flow:   Overall Study
    Arm 1: Usual Care-Active Surveillance     Arm 2: Targeted Decolonization     Arm 3: Universal Decolonization  
STARTED     16     14     13  
COMPLETED     16     13     13  
NOT COMPLETED     0     1     0  
Withdrawal by Hospital                 0                 1                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
'Number of Participant' totals reflect total Baseline and Intervention participants combined. 45 hospitals were randomized to a study group, 2 dropped due to exclusion criteria, 43 began the assigned intervention. 1 hospital withdrew during the intervention and was included in as-assigned analyses.

Reporting Groups
  Description
Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
Arm 2: Targeted Decolonization

Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+

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)

Arm 3: Universal Decolonization

Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Contact Precautions for MRSA+

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)

Total Total of all reporting groups

Baseline Measures
    Arm 1: Usual Care-Active Surveillance     Arm 2: Targeted Decolonization     Arm 3: Universal Decolonization     Total  
Number of Participants  
[units: participants]
  39296     39970     43380     122646  
Age  
[units: Years]
Median ( Inter-Quartile Range )
       
Baseline Age     65  
  ( 52 to 77 )  
  66  
  ( 53 to 77 )  
  65  
  ( 51 to 77 )  
  65  
  ( 52 to 77 )  
Intervention Age     65  
  ( 52 to 77 )  
  66  
  ( 53 to 77 )  
  65  
  ( 52 to 77 )  
  65  
  ( 52 to 77 )  
Gender, Customized [1]
[units: participants]
       
Females - Baseline     7465     7183     8314     22962  
Males - Baseline     8351     8035     9042     25428  
Females - Intervention     11176     11683     12361     35220  
Males - Intervention     12304     13069     13663     39036  
Overall Number of Participants, by Phase [2]
[units: Admissions]
       
Baseline Participants     15816     15218     17356     48390  
Intervention Participants     23480     24752     26024     74256  
[1] Proportion of female study participants, during baseline and intervention study phases.
[2] This table reflects number of admissions with an ICU stay during the Baseline and Intervention periods, separately. Please note that the table above, "Overall Number of Baseline Participants" reflects the total number of participants for which baseline characteristics were measured, across Baseline and Intervention phases combined.



  Outcome Measures
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1.  Primary:   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. ]

Measure Type Primary
Measure Title Main Outcome: Patients With Nosocomial MRSA Clinical Cultures
Measure Description Hazard ratio for ICU-attributable MRSA+ clinical cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.

Reporting Groups
  Description
Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
Arm 2: Targeted Decolonization

Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+

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)

Arm 3: Universal Decolonization

Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance , Contact Precautions for MRSA+

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)


Measured Values
    Arm 1: Usual Care-Active Surveillance     Arm 2: Targeted Decolonization     Arm 3: Universal Decolonization  
Number of Participants Analyzed  
[units: participants]
  39296     39970     43380  
Main Outcome: Patients With Nosocomial MRSA Clinical Cultures  
[units: hazard ratio]
Number ( 95% Confidence Interval )
  0.92  
  ( 0.77 to 1.10 )  
  0.75  
  ( 0.63 to 0.89 )  
  0.63  
  ( 0.52 to 0.75 )  


Statistical Analysis 1 for Main Outcome: Patients With Nosocomial MRSA Clinical Cultures
Groups [1] All groups
Method [2] Proportional-hazards models
P Value [3] 0.01
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Proportional-hazards models with shared frailties accounted for clustering within hospitals.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



2.  Secondary:   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. ]

Measure Type Secondary
Measure Title MRSA Bloodstream Infection
Measure Description Hazard ratio for ICU-attributable MRSA+ blood cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.

Reporting Groups
  Description
Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
Arm 2: Targeted Decolonization

Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+

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)

Arm 3: Universal Decolonization

Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Contact Precautions for MRSA+

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)


Measured Values
    Arm 1: Usual Care-Active Surveillance     Arm 2: Targeted Decolonization     Arm 3: Universal Decolonization  
Number of Participants Analyzed  
[units: participants]
  39296     39970     43380  
MRSA Bloodstream Infection  
[units: hazard ratio]
Number ( 95% Confidence Interval )
  1.23  
  ( 0.82 to 1.85 )  
  1.23  
  ( 0.80 to 1.90 )  
  0.72  
  ( 0.48 to 1.08 )  

No statistical analysis provided for MRSA Bloodstream Infection



3.  Secondary:   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. ]

Measure Type Secondary
Measure Title ICU-attributable All-pathogen Bloodstream Infection
Measure Description Hazard ratio for ICU-attributable positive blood culture from any pathogen, comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.

Reporting Groups
  Description
Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+
Arm 2: Targeted Decolonization

Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+

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)

Arm 3: Universal Decolonization

Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Contact Precautions for MRSA+

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)


Measured Values
    Arm 1: Usual Care-Active Surveillance     Arm 2: Targeted Decolonization     Arm 3: Universal Decolonization  
Number of Participants Analyzed  
[units: participants]
  39296     39970     43380  
ICU-attributable All-pathogen Bloodstream Infection  
[units: Hazard ratio]
Number ( 95% Confidence Interval )
  0.99  
  ( 0.84 to 1.16 )  
  0.78  
  ( 0.66 to 0.91 )  
  0.56  
  ( 0.49 to 0.65 )  

No statistical analysis provided for ICU-attributable All-pathogen Bloodstream Infection



4.  Secondary:   Urinary Tract Infections   [ Time Frame: 18-months ]
Results not yet posted.   Anticipated Posting Date:   06/2015   Safety Issue:   No

5.  Secondary:   Emergence of Resistance to Mupirocin and Chlorhexidine   [ Time Frame: 18-months ]
Results not yet posted.   Anticipated Posting Date:   03/2015   Safety Issue:   No

6.  Secondary:   Cost Effectiveness   [ Time Frame: 18-months ]
Results not yet posted.   Anticipated Posting Date:   12/2014   Safety Issue:   No

7.  Secondary:   Blood Culture Contamination   [ Time Frame: 18-months ]
Results not yet posted.   Anticipated Posting Date:   12/2014   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Susan Huang
Organization: University of California, Irvine
phone: 949-824-5073
e-mail: sshuang@uci.edu


Publications of Results:
Other Publications:

Responsible Party: Richard Platt, Harvard Pilgrim Health Care
ClinicalTrials.gov Identifier: NCT00980980     History of Changes
Other Study ID Numbers: PH000223K, HHSA2902005003I, TO #11
Study First Received: September 19, 2009
Results First Received: May 14, 2014
Last Updated: August 18, 2014
Health Authority: United States: Institutional Review Board