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

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

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

Conditions
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Skin/Soft Tissue Infections, Methicillin Resistant Staphylococcus Aureus (MRSA)

Intervention / Treatment
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* Drug: linezolid
* Drug: vancomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: linezolid|nan|
|Drug: vancomycin|nan|

What is the study measuring?
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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) |