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

Methicillin Resistant Staphylococcus Aureus (MRSA) Clinical Trial

— ZEPHYR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00084266
• Other study ID #: A5951001
• Status: Completed
• Phase: Phase 4
• First received: June 9, 2004
• Last updated: January 30, 2012
• Start date: October 2004
• Est. completion date: March 2010

Study information

• Verified date: January 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1225
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Methicillin Resistant Staphylococcus Aureus (MRSA)
• Pneumonia
• Staphylococcal Infections

Intervention

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.
• 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.

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Belgium	Pfizer Investigational Site	Brugge
Belgium	Pfizer Investigational Site	Brussels
Belgium	Pfizer Investigational Site	Gent
Belgium	Pfizer Investigational Site	Liege 1
Brazil	Pfizer Investigational Site	Salvador	BA
Brazil	Pfizer Investigational Site	Sao Jose do Rio Preto	SP
Brazil	Pfizer Investigational Site	São Paulo	SP
Chile	Pfizer Investigational Site	Santiago	Región Metropolitana
Chile	Pfizer Investigational Site	Santiago	RM
Chile	Pfizer Investigational Site	Santiago
Colombia	Pfizer Investigational Site	Barranquilla	Atlantico
Colombia	Pfizer Investigational Site	Bogota	Bogota. DC
Colombia	Pfizer Investigational Site	Bogota	Cundinamarca
Colombia	Pfizer Investigational Site	Ibague	Tolima
France	Pfizer Investigational Site	Marseille Cedex 20
France	Pfizer Investigational Site	Paris
France	Pfizer Investigational Site	Paris	Cedex 18
France	Pfizer Investigational Site	Saint Etienne Cedex 02
Germany	Pfizer Investigational Site	Goettingen
Germany	Pfizer Investigational Site	Leipzig
Germany	Pfizer Investigational Site	Leipzig
Greece	Pfizer Investigational Site	Athens
Greece	Pfizer Investigational Site	Crete
Greece	Pfizer Investigational Site	Kifisia	Athens
Greece	Pfizer Investigational Site	Thessaloniki
Hong Kong	Pfizer Investigational Site	Hong Kong
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Malaysia	Pfizer Investigational Site	Kuala Lumpur
Malaysia	Pfizer Investigational Site	Kuala Lumpur
Mexico	Pfizer Investigational Site	Ciudad Madero	Tamaulipas
Mexico	Pfizer Investigational Site	Guadalajara	Jalisco
Mexico	Pfizer Investigational Site	Mexico	DF
Mexico	Pfizer Investigational Site	Monterrey/Col. Mitras Centro	Nuevo Léon
Poland	Pfizer Investigational Site	Bytom
Poland	Pfizer Investigational Site	Katowice
Poland	Pfizer Investigational Site	Krakow
Poland	Pfizer Investigational Site	Krakow
Portugal	Pfizer Investigational Site	Almada
Portugal	Pfizer Investigational Site	Coimbra
Portugal	Pfizer Investigational Site	Lisboa
Portugal	Pfizer Investigational Site	Senhora da Hora
Puerto Rico	Pfizer Investigational Site	Ponce
Puerto Rico	Pfizer Investigational Site	San Juan
Russian Federation	Pfizer Investigational Site	Moscow	Russia
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Singapore	Pfizer Investigational Site	Unknown
South Africa	Pfizer Investigational Site	Auckland Park
South Africa	Pfizer Investigational Site	Bloefontein
South Africa	Pfizer Investigational Site	Soweto
Spain	Pfizer Investigational Site	Badalona	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Madrid
Taiwan	Pfizer Investigational Site	Kaohsiung
Taiwan	Pfizer Investigational Site	Pan-Chiao
Taiwan	Pfizer Investigational Site	Taichung
Taiwan	Pfizer Investigational Site	Taipei
Turkey	Pfizer Investigational Site	Ankara
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	Plymouth	Devon
United States	Pfizer Investigational Site	Abington	Pennsylvania
United States	Pfizer Investigational Site	Albany	New York
United States	Pfizer Investigational Site	Allentown	Pennsylvania
United States	Pfizer Investigational Site	Ann Arbor	Michigan
United States	Pfizer Investigational Site	Augusta	Georgia
United States	Pfizer Investigational Site	Augusta	Georgia
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Bethlehem	Pennsylvania
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Brandon	Florida
United States	Pfizer Investigational Site	Bronx	New York
United States	Pfizer Investigational Site	Brooklyn	New York
United States	Pfizer Investigational Site	Buffalo	New York
United States	Pfizer Investigational Site	Charleston	South Carolina
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Detroit	Michigan
United States	Pfizer Investigational Site	Detroit	Michigan
United States	Pfizer Investigational Site	Detroit	Michigan
United States	Pfizer Investigational Site	Fargo	North Dakota
United States	Pfizer Investigational Site	Fargo	North Dakota
United States	Pfizer Investigational Site	Fort Lauderdale	Florida
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Greensboro	North Carolina
United States	Pfizer Investigational Site	Hackensack	New Jersey
United States	Pfizer Investigational Site	Hazard	Kentucky
United States	Pfizer Investigational Site	Honolulu	Hawaii
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Huntsville	Alabama
United States	Pfizer Investigational Site	Irving	Texas
United States	Pfizer Investigational Site	Jackson	Florida
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Montgomery	Alabama
United States	Pfizer Investigational Site	Montgomery	Alabama
United States	Pfizer Investigational Site	Murray	Utah
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	New Albany	Indiana
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Newark	Delaware
United States	Pfizer Investigational Site	North Chicago	Illinois
United States	Pfizer Investigational Site	Oak Park	Illinois
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Orange	California
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Providence	Rhode Island
United States	Pfizer Investigational Site	Redlands	California
United States	Pfizer Investigational Site	Reno	Nevada
United States	Pfizer Investigational Site	Reno	Nevada
United States	Pfizer Investigational Site	Richmond	Virginia
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Sacramento	California
United States	Pfizer Investigational Site	Saint Louis	Missouri
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Francisco	California
United States	Pfizer Investigational Site	San Marcos	Texas
United States	Pfizer Investigational Site	Sequin	Texas
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	Springfield	Illinois
United States	Pfizer Investigational Site	Springfield	Illinois
United States	Pfizer Investigational Site	Springfield	Illinois
United States	Pfizer Investigational Site	Springfield	Massachusetts
United States	Pfizer Investigational Site	St. Loius	Missouri
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Sylvania	Ohio
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Temple	Texas
United States	Pfizer Investigational Site	Toledo	Ohio
United States	Pfizer Investigational Site	Toledo	Ohio
United States	Pfizer Investigational Site	Washington	District of Columbia
United States	Pfizer Investigational Site	Washington	District of Columbia
United States	Pfizer Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Chile,  Colombia,  France,  Germany,  Greece,  Hong Kong,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No

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