Nosocomial Pneumonia 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 nosocomial (acquired in the hospital) pneumonia due to Methicillin Resistant Staphylococcus Aureus (MRSA) in adult subjects. Subjects entered in to the study will have proven healthcare-associated methicillin-resistant Staphylococcus aureus pneumonia which will be treated with either linezolid or vancomycin.

Official Title
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Linezolid In The Treatment Of Subjects With Nosocomial Pneumonia Proven To Be Due To Methicillin-Resistant Staphylococcus Aureus

Conditions
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Methicillin Resistant Staphylococcus Aureus (MRSA)

Intervention / Treatment
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* Drug: linezolid (Zyvox)
* Drug: vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized male and female subjects with clinically documented nosocomial pneumonia proven to be due to methicillin-resistant staphylococcus aureus. Chest X-ray at baseline/screen or within 48 hours of treatment consistent with the diagnosis of pneumonia. Suitable sputum specimen defined as having less than 10 squamous epithelial cells and greater or equal 25 leukocytes or have a culture taken by an invasive technique within 24 hours of study entry. Exclusion Criteria: Subjects who were treated with a previous antibiotic with MRSA activity (other than linezolid or vancomycin) for more than 48 hours, unless documented to be a treatment failure (72 hours of treatment and not responding). Subjects with severe neutropenia (<500 cells/mm3) Subjects with hypersensitivity to oxazolidinones or vancomycin.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Subjects receiving linezolid for the treatment phase of the study | Drug: linezolid (Zyvox)<br>* Subjects to receive either linezolid 600 mg IV (Intravenous) or PO (orally) q 12 h (every 12 hours) for 7-14 days, except in cases of documented bacteremia where it could be extended to 21 days based upon investigator's discretion.<br>* Other names: Zyvox, linezolid;|
| Active Comparator: 2<br>Subjects receiving vancomycin for the treatment phase of the study | Drug: vancomycin<br>* Subjects to receive vancomycin 15mg/kg IV (Intravenous) q12h (every 12 hours), adjusted for renal function, for 7-14 days, except in cases of documented bacteremia where it could be extended to 21 days based upon investigator's discretion.<br>|

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 PP Population | Clinical response was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation timepoint. Clinical response was evaluated at EOS Visit as Cure: resolution of clinical signs/symptoms of pneumonia when compared with baseline; Failure: persistence/progression of baseline signs/symptoms of pneumonia or baseline radiographic abnormalities after atleast 2 days of treatment; development of new pulmonary/extrapulmonary clinical findings consistent with active infection; Unknown:extenuating circumstances precluding classification to 1 of the above. | EOS (7-30 days after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome in Participants With Baseline MRSA at EOS for mITT Population | Clinical response was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation timepoint. Clinical response was evaluated at EOS Visit as Cure: resolution of clinical signs/symptoms of pneumonia when compared with baseline; Failure: persistence/progression of baseline signs/symptoms of pneumonia or baseline radiographic abnormalities after atleast 2 days of treatment; development of new pulmonary/extrapulmonary clinical findings consistent with active infection; Unknown:extenuating circumstances precluding classification to 1 of the above. | EOS (7-30 days after last dose) | 
| Clinical Outcome in Participants With Baseline MRSA at End of Treatment (EOT) for PP Population | Clinical response evaluated at EOT visit as Cure:resolution of clinical sign/symptoms of pneumonia when compared with baseline;Improvement: in 2 or more clinical sign/symptoms of pneumonia when compared with baseline,improvement/lack of progression of all chest X-ray abnormalities,Failure: persistence/ progression of baseline signs/symptoms of pneumonia or baseline radiographic abnormalities after atleast 2 days of treatment; development of new pulmonary/extrapulmonary clinical findings consistent with active infection;Unknown: extenuating circumstances precluding classification to 1 of above. | EOT (within 72 hours of last dose) | 
| Clinical Outcome in Participants With Baseline MRSA at EOT for mITT Population | Clinical response evaluated at EOT visit as Cure:resolution of clinical sign/symptoms of pneumonia when compared with baseline;Improvement: in 2 or more clinical sign/symptoms of pneumonia when compared with baseline,improvement/lack of progression of all chest X-ray abnormalities,Failure: persistence/ progression of baseline signs/symptoms of pneumonia or baseline radiographic abnormalities after atleast 2 days of treatment; development of new pulmonary/extrapulmonary clinical findings consistent with active infection;Unknown: extenuating circumstances precluding classification to 1 of above. | EOT (within 72 hours of last dose) | 
| Microbiological Outcome in Participants With Baseline MRSA at EOS for PP Population | Microbiological response assessed at participant level.Eradication:baseline isolate not present in repeat culture from original infection site;Presumed Eradication:clinical response of cure precluded availability of specimen for culture;Persistence:baseline isolate present in repeat culture;Presumed Persistence:culture data not available for participant with clinical response of failure;Superinfection:culture from primary infection site had new pathogen not identified as baseline isolate and clinical response was failure;Indeterminate:any participant who cannot be classified into any of above. | EOS (7-30 days after last dose) | 
| Microbiological Outcome in Participants With Baseline MRSA at EOS for mITT Population | Microbiological response assessed at participant level.Eradication:baseline isolate not present in repeat culture from original infection site;Presumed Eradication:clinical response of cure precluded availability of specimen for culture;Persistence:baseline isolate present in repeat culture;Presumed Persistence:culture data not available for participant with clinical response of failure;Superinfection:culture from primary infection site had new pathogen not identified as baseline isolate and clinical response was failure;Indeterminate:any participant who cannot be classified into any of above. | EOS (7-30 days after last dose) | 
| Microbiological Outcome in Participants With Baseline MRSA at EOT for PP Population | Microbiological response assessed at participant level.Eradication:baseline isolate not present in repeat culture from original infection site;Presumed Eradication:clinical response of cure precluded availability of specimen for culture;Persistence:baseline isolate present in repeat culture;Presumed Persistence:culture data not available for participant with clinical response of failure;Superinfection:culture from primary infection site had new pathogen not identified as baseline isolate and clinical response was failure;Indeterminate:any participant who cannot be classified into any of above. | EOT (within 72 hours of last dose) | 
| Microbiological Outcome in Participants With Baseline MRSA at EOT for mITT Population | Microbiological response assessed at participant level.Eradication:baseline isolate not present in repeat culture from original infection site;Presumed Eradication:clinical response of cure precluded availability of specimen for culture;Persistence:baseline isolate present in repeat culture;Presumed Persistence:culture data not available for participant with clinical response of failure;Superinfection:culture from primary infection site had new pathogen not identified as baseline isolate and clinical response was failure;Indeterminate:any participant who cannot be classified into any of above. | EOT (within 72 hours of last dose) | 
| Number of Participants With Clinical Signs and Symptoms at 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 (mild to severe) of nosocomial pneumonia included cough; production of purulent sputum or change in character of sputum;auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony); and dyspnea, tachypnea, or hypoxemia with PaO2 <60 mmHg or worsening gas exchange or increased oxygen requirements; pleuritic chest pain; chills/rigors; and decreased breath sounds. | EOS (7-30 days after last dose) | 
| Number of Participants With Clinical Signs and Symptoms at 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 (mild to severe) of nosocomial pneumonia included cough; production of purulent sputum or change in character of sputum;auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony); and dyspnea, tachypnea, or hypoxemia with PaO2 <60 mmHg or worsening gas exchange or increased oxygen requirements; pleuritic chest pain; chills/rigors; and decreased breath sounds. | EOS (7-30 days after last dose) | 
| Number of Participants With Clinical Signs and Symptoms at EOT for PP Population | Participant's clinical evaluation of signs and symptoms were based on global assessment by investigator at specific timepoints. Signs and symptoms (mild to severe) of nosocomial pneumonia included cough; production of purulent sputum or change in character of sputum;auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony); and dyspnea, tachypnea, or hypoxemia with PaO2 <60 mmHg or worsening gas exchange or increased oxygen requirements; pleuritic chest pain; chills/rigors; and decreased breath sounds. | EOT (within 72 hours of last dose) | 
| Number of Participants With Clinical Signs and Symptoms at EOT for mITT Population | Participant's clinical evaluation of signs and symptoms were based on global assessment by investigator at specific timepoints. Signs and symptoms (mild to severe) of nosocomial pneumonia included cough; production of purulent sputum or change in character of sputum;auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony); and dyspnea, tachypnea, or hypoxemia with PaO2 <60 mmHg or worsening gas exchange or increased oxygen requirements; pleuritic chest pain; chills/rigors; and decreased breath sounds. | EOT (within 72 hours of last dose) | 
| Survival Status Estimated by Kaplan-Meier Analysis for PP Population | For each participant, time to death was estimated from baseline to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. The distribution of survival was estimated for the treatment groups using the Kaplan-Meier, product-limit method and compared between the treatment groups using the log rank statistic. | From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. | 
| Survival Status Estimated by Kaplan-Meier Analysis for mITT Population | For each participant, time to death was estimated from baseline to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. The distribution of survival was estimated for the treatment groups using the Kaplan-Meier, product-limit method and compared between the treatment groups using the log rank statistic. | From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. | 
| Survival Status Estimated by Kaplan-Meier Analysis for ITT Population | For each participant, time to death was estimated from baseline to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. The distribution of survival was estimated for the treatment groups using the Kaplan-Meier, product-limit method and compared between the treatment groups using the log rank statistic. | From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 days after last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcal pneumonia, Methicillin-resistant staphylococcal pneumonia, healthcare-associated pneumonia