Project CLEAR - Changing Lives by Eradicating Antibiotic Resistance (CLEAR)

This randomized controlled trial will compare strategies to reduce the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection and re-hospitalization in MRSA carriers. This trial will provide critical answers about the role of decolonization versus standard-of-care education in preventing MRSA infections in the large group of high risk MRSA-positive patients being discharged from hospitals. Findings could potentially impact best practice for the 1.8 million MRSA carriers who are discharged from US hospitals each year.

Study Overview

• Status: Completed
• Conditions: Methicillin-resistant Staphylococcus Aureus
• Intervention / Treatment: Drug: MRSA Decolonization; Behavioral: Standard-of-Care Education

Detailed Description

This randomized controlled trial will compare strategies to reduce the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection and re-hospitalization in MRSA carriers. This trial will provide critical answers about the role of decolonization versus standard-of-care education in preventing MRSA infections in the large group of high risk MRSA+ patients being discharged from hospitals. Findings could potentially impact best practice for the 1.8 million MRSA carriers who are discharged from US hospitals each year.

Specific Aims:

Methicillin-resistant Staphylococcus aureus (MRSA) is arguably the most important single pathogen in healthcare-associated infection when accounting for virulence, prevalence, diversity of disease spectrum, and propensity for widespread transmission. MRSA infection causes or complicates 300,000 hospitalizations each year [Klein, Smith, Laxminarayan], a number which has doubled in the past five years. An additional 1.5 million hospitalized patients either acquire or already harbor the pathogen without current infection. Altogether, these 1.8 million MRSA inpatient carriers experience a high amount of MRSA invasive disease in the year following discharge. Due to increased delivery of complex medical care at home or other post-hospital settings, more and more patients experience serious healthcare-associated morbidity after hospital discharge.[Huang, Platt; Huang, Hinrichsen, Stulgis et al.] In fact, over 80% of patients admitted for MRSA infection have had prior healthcare exposures and are at high risk for repeated MRSA infection.[Huang, Platt; Huang, Hinrichsen, Stulgis et al.; Klevens, Morrison, Nadle, et al.]

Project CLEAR compares two strategies to reduce infection and re-hospitalization due to MRSA among patients being discharged from hospitals. Our trial will compare a long-term regimen aimed at eradicating MRSA body reservoirs with patient education on general hygiene and self care, which is the current standard of care. Our specific aims are:

• To conduct a randomized controlled trial of serial decolonization versus standard-of-care patient education among MRSA carriers upon hospital discharge to reduce post-discharge MRSA infection and re-hospitalization for one year
• To identify predictors of a) infection or re-hospitalization due to MRSA, and b) successful MRSA decolonization, including patient demographics, comorbidities, medical devices, risk behaviors, socioeconomic status, and colonizing MRSA genotype
• To estimate medical and non-medical costs of MRSA infection among MRSA carriers and evaluate the potential for cost savings associated with decolonization

• Study Type: Interventional
• Enrollment (Actual): 2140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Aliso Viejo, California, United States, 92656
      • Covington Care Center
    • Anaheim, California, United States, 92804
      • West Anaheim Extended Care
    • Downey, California, United States, 90241
      • Downey Regional Medical Center
    • Fountain Valley, California, United States, 92708
      • Orange Coast Memorial Medical Center
    • Fountain Valley, California, United States, 92708
      • Fountain Valley Regional Hospital & Medical Center
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • Garden Grove, California, United States, 92840
      • Chapman Care Center
    • Garden Grove, California, United States, 92843
      • Pacific Haven HealthCare Center
    • Irvine, California, United States, 92612
      • Regents Point at Windcrest
    • Laguna Hills, California, United States, 92653
      • Saddleback Memorial Medical Center - Laguna Hills
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Long Beach, California, United States, 90813
      • St. Mary Medical Center
    • Mission Viejo, California, United States, 92691
      • Mission Hospital
    • Newport Beach, California, United States, 92658
      • Hoag Memorial Hospital Presbyterian
    • Norwalk, California, United States, 90650
      • Villa Elena Health Care Center
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Clemente, California, United States, 92673
      • Saddleback Memorial Medical Center - San Clemente
    • San Pedro, California, United States, 90732
      • Little Company of Mary - San Pedro
    • Santa Ana, California, United States, 92707
      • Country Villa Plaza
    • Santa Ana, California, United States, 92707
      • Royale Healthcare
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
    • Torrance, California, United States, 90505
      • Torrance Memorial Medical Center
    • Torrance, California, United States, 90732
      • Providence Little Company of Mary Medical Center
    • Ventura, California, United States, 93003
      • Ventura County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) At least 18 years old
• 2) Have had a positive culture (a type of test) for MRSA during recent hospital admission or within the 30 days prior to admission or following discharge
• 3) Able to give consent or have a primary caregiver provide consent
• 4) Able to bathe or shower or have this consistently performed by a willing caregiver

Exclusion Criteria:

• 1) Known allergies to chlorhexidine or mupirocin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MRSA Decolonization; Participants in this arm will be instructed to complete a decolonization regimen that will involve a 5-day application of nasal mupirocin, oral CHG rinse, and CHG body wash twice a month.	Drug: MRSA Decolonization; Participants in this arm will be instructed to complete a decolonization regimen that will involve a 5-day application of nasal mupirocin, oral CHG rinse, and CHG body wash twice a month.
Active Comparator: Education Arm; Patients randomized to standard education will receive a binder with MRSA educational materials which will include or be based upon CDC guidance for MRSA patients at home. In addition, educational material on hygiene practices to prevent MRSA infection will be provided.	Behavioral: Standard-of-Care Education; Patients randomized to standard education will receive a binder with MRSA educational materials which will include or be based upon CDC guidance for MRSA patients at home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to MRSA Infection	Time in days to MRSA inpatient or outpatient infection (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to infection; the results we are reporting are number of participants who had an infection event at one year post discharge)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to All-cause Infection (Steering Committee Modified Oct 2011)	Time in days to all-cause infection (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to infection; the results we are reporting are number of participants who had an infection event at one year)	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of MRSA Infections	Event count of outpatient and inpatient MRSA infections occurring after enrollment	1 year
Rehospitalization Due to MRSA Infection	Time in days to rehospitalization due to MRSA infection	1 year
Cost and Cost Savings Associated With Post-discharge MRSA Decolonization	Medical and non-medical costs of MRSA infection within the 1 year follow up period	1 year
Number of All-cause Infections (Steering Committee Modified Oct 2011)	Event count of all-cause infections occurring after enrollment	1 year

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: Agency for Healthcare Research and Quality (AHRQ)
• Investigators: Principal Investigator: Susan S Huang, MD, MPH, University of California, Irivne - School of Medicine

Publications and helpful links

General Publications

• Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71. doi: 10.1001/jama.298.15.1763.
• Klein E, Smith DL, Laxminarayan R. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg Infect Dis. 2007 Dec;13(12):1840-6. doi: 10.3201/eid1312.070629.
• Huang SS, Platt R. Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization. Clin Infect Dis. 2003 Feb 1;36(3):281-5. doi: 10.1086/345955. Epub 2003 Jan 17.
• Huang SS, Hinrichsen VH, Stulgis L, Miroshnik I, Datta R, Watson K, Platt R. Methicillin-resistant Staphylococcus aureus Infection in the Year Following Detection of Carriage (oral presentation). Society of Healthcare Epidemiology of America Annual Meeting (Chicago, IL), March 18-21, 2006.
• Huang SS, Singh R, McKinnell JA, Park S, Gombosev A, Eells SJ, Gillen DL, Kim D, Rashid S, Macias-Gil R, Bolaris MA, Tjoa T, Cao C, Hong SS, Lequieu J, Cui E, Chang J, He J, Evans K, Peterson E, Simpson G, Robinson P, Choi C, Bailey CC Jr, Leo JD, Amin A, Goldmann D, Jernigan JA, Platt R, Septimus E, Weinstein RA, Hayden MK, Miller LG; Project CLEAR Trial. Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers. N Engl J Med. 2019 Feb 14;380(7):638-650. doi: 10.1056/NEJMoa1716771.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: September 23, 2010
• First Submitted That Met QC Criteria: September 23, 2010
• First Posted (Estimate): September 27, 2010

Study Record Updates

• Last Update Posted (Actual): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: MRSA; Methicillin-resistant Staphylococcus aureus
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections
• Other Study ID Numbers: 2010-7710