Skin Structure Infections With Suspected or Proven Methicillin-Resistant Staphylococcus Aureus (MRSA)

Linezolid in the Treatment of Subjects With Complicated Skin and Soft Tissue Infections Proven to be Due to Methicillin-Resistant Staphylococcus Aureus

To determine if linezolid is superior to vancomycin in the treatment of complicated skin and soft tissue infections due to MRSA in adult subjects

Study Overview

• Status: Completed
• Conditions: Skin/Soft Tissue Infections; Methicillin Resistant Staphylococcus Aureus (MRSA)
• Intervention / Treatment: Drug: vancomycin; Drug: linezolid

• Study Type: Interventional
• Enrollment (Actual): 1077
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Pfizer Investigational Site
  • Buenos Aires, Argentina, C1425DQK
    • Pfizer Investigational Site
  • Cordoba, Argentina, 5000
    • Pfizer Investigational Site
  • Buenos Aires
    • Loma Hermosa, Buenos Aires, Argentina, 1653
      • Pfizer Investigational Site
• Belgium
  • Charleroi, Belgium, 6000
    • Pfizer Investigational Site
  • Gent, Belgium, 9000
    • Pfizer Investigational Site
  • Montigny-le-Tilleul, Belgium, 6110
    • Pfizer Investigational Site
• Brazil
  • SP
    • São José do Rio Preto, SP, Brazil, 15090-000
      • Pfizer Investigational Site
    • São Paulo, SP, Brazil, 01221-020
      • Pfizer Investigational Site
• Chile
  • Santiago, Chile
    • Pfizer Investigational Site
  • Santiago
    • Providencia, Santiago, Chile
      • Pfizer Investigational Site
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Pfizer Investigational Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Pfizer Investigational Site
  • Santander
    • Floridablanca, Santander, Colombia
      • Pfizer Investigational Site
• Italy
  • Genova, Italy, 16132
    • Pfizer Investigational Site
  • Napoli, Italy, 80131
    • Pfizer Investigational Site
  • Roma, Italy, 00168
    • Pfizer Investigational Site
  • Roma, Italy, 00149
    • Pfizer Investigational Site
  • Udine, Italy, 33100
    • Pfizer Investigational Site
  • Varese, Italy, 21100
    • Pfizer Investigational Site
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Pfizer Investigational Site
  • Kuala Lumpur, Malaysia, 50603
    • Pfizer Investigational Site
• Mexico
  • DF
    • Mexico, DF, Mexico, 14000
      • Pfizer Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Pfizer Investigational Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64020
      • Pfizer Investigational Site
• Portugal
  • Amadora, Portugal, 2720
    • Pfizer Investigational Site
  • Coimbra, Portugal, 3090
    • Pfizer Investigational Site
  • Lisboa, Portugal
    • Pfizer Investigational Site
  • Lisboa, Portugal, 1449-005
    • Pfizer Investigational Site
  • Almada
    • Pragal, Almada, Portugal, 2800-525
      • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 119048
    • Pfizer Investigational Site
  • Smolensk, Russian Federation
    • Pfizer Investigational Site
• Singapore
  • Singapore, Singapore, 529889
    • Pfizer Investigational Site
• South Africa
  • Johannesburg, South Africa, 2113
    • Pfizer Investigational Site
  • Parow, South Africa, 7499
    • Pfizer Investigational Site
  • Pretoria, South Africa, 0001
    • Pfizer Investigational Site
  • Pretoria, South Africa, 0184
    • Pfizer Investigational Site
  • Western Province
    • Kuilsriver, Western Province, South Africa, 7580
      • Pfizer Investigational Site
• Spain
  • Cordoba, Spain, 14004
    • Pfizer Investigational Site
  • Gerona, Spain, 17007
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Pfizer Investigational Site
  • Leeds, United Kingdom, LS1 3EX
    • Pfizer Investigational Site
  • Hampshire
    • Winchester, Hampshire, United Kingdom, SO22 5DG
      • Pfizer Investigational Site
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Pfizer Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Pfizer Investigational Site
  • California
    • Los Angeles, California, United States, 90033
      • Pfizer Investigational Site
    • Palm Springs, California, United States, 92262
      • Pfizer Investigational Site
    • Rancho Mirage, California, United States, 92270
      • Pfizer Investigational Site
    • San Pedro, California, United States, 90732
      • Pfizer Investigational Site
    • Santa Fe Springs, California, United States, 90670
      • Pfizer Investigational Site
    • Sylmar, California, United States, 91342
      • Pfizer Investigational Site
    • Torrance, California, United States, 90502
      • Pfizer Investigational Site
    • Torrance, California, United States, 90509
      • Pfizer Investigational Site
    • Torrance, California, United States, 90503
      • Pfizer Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Pfizer Investigational Site
    • Denver, Colorado, United States, 80205
      • Pfizer Investigational Site
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Pfizer Investigational Site
    • Hartford, Connecticut, United States, 06106
      • Pfizer Investigational Site
    • New Haven, Connecticut, United States, 06510
      • Pfizer Investigational Site
    • New Haven, Connecticut, United States, 06515
      • Pfizer Investigational Site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Pfizer Investigational Site
    • Melbourne, Florida, United States, 32901
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33136
      • Pfizer Investigational Site
    • Pensacola, Florida, United States, 32501-6390
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Pfizer Investigational Site
    • Augusta, Georgia, United States, 30909
      • Pfizer Investigational Site
    • Blue Ridge, Georgia, United States, 30513
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pfizer Investigational Site
    • Honolulu, Hawaii, United States, 96817
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Pfizer Investigational Site
    • Decatur, Illinois, United States, 62526
      • Pfizer Investigational Site
    • Hines, Illinois, United States, 60141
      • Pfizer Investigational Site
    • Maywood, Illinois, United States, 60153
      • Pfizer Investigational Site
    • North Chicago, Illinois, United States, 60064
      • Pfizer Investigational Site
    • Northlake, Illinois, United States, 60164
      • Pfizer Investigational Site
    • Springfield, Illinois, United States, 62701
      • Pfizer Investigational Site
    • Springfield, Illinois, United States, 62702
      • Pfizer Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Pfizer Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40202-1798
      • Pfizer Investigational Site
    • Louisville, Kentucky, United States, 40222
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pfizer Investigational Site
    • Baltimore, Maryland, United States, 21237
      • Pfizer Investigational Site
    • Baltimore, Maryland, United States, 21230
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Pfizer Investigational Site
    • West Roxbury, Massachusetts, United States, 02132
      • Pfizer Investigational Site
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Pfizer Investigational Site
    • Lansing, Michigan, United States, 48912
      • Pfizer Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422-2998
      • Pfizer Investigational Site
    • Mpls, Minnesota, United States, 55422
      • Pfizer Investigational Site
    • St. Paul, Minnesota, United States, 55101
      • Pfizer Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Pfizer Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Pfizer Investigational Site
    • Lincoln, Nebraska, United States, 46851
      • Pfizer Investigational Site
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • Pfizer Investigational Site
  • New York
    • Stony Brook, New York, United States, 11794
      • Pfizer Investigational Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Pfizer Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44304
      • Pfizer Investigational Site
    • Akron, Ohio, United States, 44309
      • Pfizer Investigational Site
    • Akron, Ohio, United States, 44310
      • Pfizer Investigational Site
    • Columbus, Ohio, United States, 43214
      • Pfizer Investigational Site
    • Columbus, Ohio, United States, 43215
      • Pfizer Investigational Site
    • Toledo, Ohio, United States, 43608
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19141
      • Pfizer Investigational Site
    • West Reading, Pennsylvania, United States, 19611
      • Pfizer Investigational Site
  • Tennessee
    • Ducktown, Tennessee, United States, 37326
      • Pfizer Investigational Site
    • Jackson, Tennessee, United States, 38301
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75235
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75390-9016
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76107
      • Pfizer Investigational Site
    • Forth Worth, Texas, United States, 76104
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
  • Utah
    • St. George, Utah, United States, 84770
      • Pfizer Investigational Site
    • St. George, Utah, United States, 84790
      • Pfizer Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98431
      • Pfizer Investigational Site
• Venezuela
  • Valencia, Venezuela, 2002
    • Pfizer Investigational Site
  • Estado Bolívar
    • Ciudad Bolívar, Estado Bolívar, Venezuela, 8001
      • Pfizer Investigational Site
  • Estado Miranda
    • Distrito Capital, Estado Miranda, Venezuela, 1040
      • Pfizer Investigational Site
    • Distrito Capital, Estado Miranda, Venezuela, 1070
      • Pfizer Investigational Site
  • Estado Zulia
    • Maracaibo, Estado Zulia, Venezuela, 4002
      • Pfizer Investigational Site

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:

• Male and female subjects with signs or symptoms consistent with infection, and if available, laboratory findings consistent with staphylococcal infection (e.g., Gram stain and culture results).
• Signs and symptoms consistent with infection
• Infection suspected to be due to Methicillin Resistant Staphylococcus Aureus

Exclusion Criteria:

• Subjects who were treated with a previous antibiotic (systemic or topical) with MRSA activity (other than linezolid or vancomycin) for more than 24 hours and treatment extended into the 72 hour period prior to the first dose of study drug, unless documented to be a treatment failure (72 hours of treatment and not responding).
• Subjects with uncomplicated skin or superficial skin structure infection such as superficial/simple cellulitis, impetiginous lesion, furuncle, or simple abscess that only need surgical drainage for cure.
• Subjects excluded with necrotizing fasciitis, gas gangrene, osteomyelitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcome in Participants With Baseline Methicillin-Resistant Staphylococcus Aureus (MRSA) at End of Study (EOS) for Per-Protocol (PP) Population	Clinical response (CR) was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At EOS, CR was evaluated as "success" (cure: resolution of clinical signs or (/) symptoms of infection when compared to baseline); "failure": persistence/progression of baseline signs/symptoms of infection after at least 2 days of treatment/development of new clinical findings consistent with active infection; "unknown": extenuating circumstances precluding classification to 1 of above. "Unknown" was excluded from present analysis.	EOS (6 to 28 days after the last dose of study drug)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcome in Participants With Baseline MRSA at End of Treatment (EOT) for PP Population	CR evaluated at EOT visit as "success" (cure: resolution of clinical sign/symptoms of infection when compared with baseline; and improvement: 2/more improvement in clinical sign/symptoms of infection when compared with baseline); "failure": persistence/progression of baseline signs/symptoms of infection after at least 2 days of treatment/development of new clinical findings consistent with active infection; "unknown": extenuating circumstances precluding classification to 1 of above. "Unknown": excluded from present analysis.	EOT (within 72 hours of last dose of study drug)
Clinical Outcome in Participants With Baseline MRSA at EOS for Modified-Intent to Treat (mITT) Population	CR was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At EOS, CR was evaluated as "success" (cure: resolution of clinical signs/symptoms of infection when compared to baseline); "failure": persistence/progression of baseline signs/symptoms of infection after at least 2 days of treatment/development of new clinical findings consistent with active infection; "unknown": extenuating circumstances precluding classification to 1 of above. "Unknown" was excluded from present analysis.	EOS (6 to 28 days after the last dose of study drug)
Clinical Outcome in Participants With Baseline MRSA at EOT for mITT Population	CR evaluated at EOT visit as "success" (cure: resolution of clinical sign/symptoms of infection when compared with baseline; and improvement: 2/more improvement in clinical sign/symptoms of infection when compared with baseline); "failure": persistence/progression of baseline signs/symptoms of infection after at least 2 days of treatment/development of new clinical findings consistent with active infection; "unknown": extenuating circumstances precluding classification to 1 of above. "Unknown": excluded from present analysis.	EOT (within 72 hours of last dose of study drug)
Microbiological Outcome in Participants With Baseline MRSA at EOS for PP Population	Microbiological outcome dichotomized to "success" (eradication: absence of baseline isolate (BI) in culture of original infection site (IS); presumed eradication: participant cured and no specimen available for culture; superinfection: clinically failed or improved with new pathogen identified from primary IS other than BI; colonization: isolate was present but not producing infection) and "failure" (persistence: BI present in original IS; presumed persistence: clinically failed and no specimen available for culture; recurrence: presence of isolate at EOS, that was eradicated at EOT).	EOS (6 to 28 days after the last dose of study drug)
Microbiological Outcome in Participants With Baseline MRSA at EOT for PP Population	Microbiological outcome dichotomized to "success" (eradication: absence of baseline isolate (BI) in culture of original infection site (IS); presumed eradication: participant cured and no specimen available for culture; superinfection: clinically failed or improved with new pathogen identified from primary IS other than BI; colonization: isolate was present but not producing infection) and "failure" (persistence: BI present in original IS; presumed persistence: clinically failed and no specimen available for culture).	EOT (within 72 hours of last dose of study drug)
Microbiological Outcome in Participants With Baseline MRSA at EOS for mITT Population	Microbiological outcome dichotomized to "success" (eradication: absence of baseline isolate (BI) in culture of original infection site (IS); presumed eradication: participant cured and no specimen available for culture; superinfection: clinically failed or improved with new pathogen identified from primary IS other than BI; colonization: isolate was present but not producing infection) and "failure" (persistence: BI present in original IS; presumed persistence: clinically failed and no specimen available for culture; recurrence: presence of isolate at EOS, that was eradicated at EOT).	EOS (6 to 28 days after the last dose of study drug)
Microbiological Outcome in Participants With Baseline MRSA at EOT for mITT Population	Microbiological outcome dichotomized to "success" (eradication: absence of baseline isolate (BI) in culture of original infection site (IS); presumed eradication: participant cured and no specimen available for culture; superinfection: clinically failed or improved with new pathogen identified from primary IS other than BI; colonization: isolate was present but not producing infection) and "failure" (persistence: BI present in original IS; presumed persistence: clinically failed and no specimen available for culture).	EOT (within 72 hours of last dose of study drug)
Number of Participants With Clinical Signs and Symptoms at EOT and EOS for PP Population	Participant's clinical evaluation of signs and symptoms were based on global assessment by investigator at specific timepoints. Signs and symptoms of an active skin or soft tissue infection caused by suspected MRSA included purulent discharge, nonpurulent discharge, erythema, swelling, induration, tenderness, pain and local skin warmth. It was recorded by the sponsor using wound parameter score ranging from 0 to 3; "0= none, 1= mild, 2= moderate and 3= severe".	EOT (within 72 hours of last dose of study drug), EOS (6 to 28 days after the last dose of study drug)
Number of Participants With Clinical Signs and Symptoms at EOT and EOS for mITT Population	Participant's clinical evaluation of signs and symptoms were based on global assessment by investigator at specific timepoints. Signs and symptoms of an active skin or soft tissue infection caused by suspected MRSA included purulent discharge, nonpurulent discharge, erythema, swelling, induration, tenderness, pain and local skin warmth. It was recorded using wound parameter score ranging from 0 to 3; "0= none, 1= mild, 2= moderate and 3= severe".	EOT (within 72 hours of last dose of study drug), EOS (6 to 28 days after the last dose of study drug)
Duration of Hospital Stay for PP Population	Duration of Hospital Stay was defined as the number of days the participant was cared as an inpatient in the hospital during the maximum 34 days of the study period. The number of days in the hospital was counted from start of study medication to date of discharge or last date known to be in the hospital (for missing discharge dates and participants who died) or Day 34 for participants who continued hospitalization beyond EOS period.	Baseline up to EOS (6 to 28 days after the last dose of study drug)
Duration of Hospital Stay for mITT Population	Duration of Hospital Stay was defined as the number of days the participant was cared as an inpatient in the hospital during the maximum 34 days of the study period. The number of days in the hospital was counted from start of study medication to date of discharge or last date known to be in the hospital (for missing discharge dates and participants who died) or Day 34 for participants who continued hospitalization beyond EOS period.	Baseline up to EOS (6 to 28 days after the last dose of study drug)
Duration of Intravenous Therapy for PP Population	Duration of intravenous antibiotic treatment was measured as the number of days intravenous doses of study medication was administered, before and after discharge.	Baseline up to EOS (6 to 28 days after the last dose of study drug)
Duration of Intravenous Therapy for mITT Population	Duration of intravenous antibiotic treatment was measured as the number of days intravenous doses of study medication was administered, before and after discharge.	Baseline up to EOS (6 to 28 days after the last dose of study drug)
Number of Participants Using Medical Resources	Medical resources utilization included a daily log of the participants' location in the hospital and outside of the hospital (non-hospital location), adjusted duration of stay (difference between duration of stay and the duration of discharge delay) and daily log of study drug dosing.	Baseline up to EOS (6 to 28 days after the last dose of study drug)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Puzniak LA, Morrow LE, Huang DB, Barreto JN. Impact of weight on treatment efficacy and safety in complicated skin and skin structure infections and nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Ther. 2013 Oct;35(10):1557-70. doi: 10.1016/j.clinthera.2013.08.001. Epub 2013 Sep 3.
• Itani KM, Biswas P, Reisman A, Bhattacharyya H, Baruch AM. Clinical efficacy of oral linezolid compared with intravenous vancomycin for the treatment of methicillin-resistant Staphylococcus aureus-complicated skin and soft tissue infections: a retrospective, propensity score-matched, case-control analysis. Clin Ther. 2012 Aug;34(8):1667-73.e1. doi: 10.1016/j.clinthera.2012.06.018. Epub 2012 Jul 6.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): July 1, 2007

Study Registration Dates

• First Submitted: July 9, 2004
• First Submitted That Met QC Criteria: July 12, 2004
• First Posted (ESTIMATE): July 13, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): August 8, 2012
• Last Update Submitted That Met QC Criteria: June 29, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Soft Tissue Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Vancomycin; Linezolid
• Other Study ID Numbers: A5951002