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Nosocomial Pneumonia With Suspected Or Proven Methicillin-Resistant Staphylococcus Aureus (MRSA) (ZEPHYR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00084266
First received: June 9, 2004
Last updated: January 30, 2012
Last verified: January 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Methicillin Resistant Staphylococcus Aureus (MRSA)
 Drug: linezolid (Zyvox)
Drug: vancomycin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Linezolid In The Treatment Of Subjects With Nosocomial Pneumonia Proven To Be Due To Methicillin-Resistant Staphylococcus Aureus

Resource links provided by NLM:

MedlinePlus related topics: Pneumonia
U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Clinical Outcome in Participants With Baseline Methicillin Resistant Staphylococcus Aureus (MRSA) at End of Study (EOS) for PP Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Clinical Outcome in Participants With Baseline MRSA at EOS for mITT Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: No ]
    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.

  • Clinical Outcome in Participants With Baseline MRSA at End of Treatment (EOT) for PP Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: No ]
    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.

  • Clinical Outcome in Participants With Baseline MRSA at EOT for mITT Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Outcome in Participants With Baseline MRSA at EOS for PP Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Outcome in Participants With Baseline MRSA at EOS for mITT Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Outcome in Participants With Baseline MRSA at EOT for PP Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: No ]
    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.

  • Microbiological Outcome in Participants With Baseline MRSA at EOT for mITT Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Clinical Signs and Symptoms at EOS for PP Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinical Signs and Symptoms at EOS for mITT Population [ Time Frame: EOS (7-30 days after last dose) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinical Signs and Symptoms at EOT for PP Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinical Signs and Symptoms at EOT for mITT Population [ Time Frame: EOT (within 72 hours of last dose) ] [ Designated as safety issue: Yes ]
    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.

  • Survival Status Estimated by Kaplan-Meier Analysis for PP Population [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Survival Status Estimated by Kaplan-Meier Analysis for mITT Population [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Survival Status Estimated by Kaplan-Meier Analysis for ITT Population [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 1225
Study Start Date: October 2004
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Subjects receiving linezolid for the treatment phase of the study
 Drug: linezolid (Zyvox)
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.
Other Name: Zyvox, linezolid
Active Comparator: 2
Subjects receiving vancomycin for the treatment phase of the study
 Drug: vancomycin
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00084266

  Show 177 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00084266     History of Changes
Other Study ID Numbers: A5951001
Study First Received: June 9, 2004
Results First Received: March 10, 2011
Last Updated: January 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Staphylococcal pneumonia
Methicillin-resistant staphylococcal pneumonia
healthcare-associated pneumonia

Additional relevant MeSH terms:
Pneumonia
Staphylococcal Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Methicillin
Vancomycin
 Linezolid
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013