inezolid In The Treatment Of Subjects With Nosocomial Pneumonia Proven To Be Due To Methicillin-Resistant Staphylococcus Aureus - N/A

• Conditions: MRSA Infection - Nosocomial Pneumonia; MedDRA version: 7.0Level: LLTClassification code 10052596

• Registration Number: EUCTR2004-000827-13-DE
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-09-26
• Last Update Posted: 4 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

Male and female subjects with a diagnosis of nosocomial pneumonia meeting all criteria listed below will be included in the study.

Hospitalized (in acute, sub-acute or long-term care facility) males and females aged 18 years of age and over

Subject must have clinically documented
• Nosocomial pneumonia (NP) defined as pneumonia with clinical picture onset = 48 hours after hospitalization in an acute in-patient healthcare facility. Subject may also be enrolled upon transfer from another acute care facility if the clinical picture onset of pneumonia was after they were hospitalized at that facility for = 48 hours
OR
• Healthcare-associated pneumonia (HCAP) defined as pneumonia acquired in a long-term care or sub-acute/intermediate healthcare facility (eg., nursing home, rehabilitation center) or in subject who is admitted with pneumonia following a recent hospitalization (discharged within 90 days of current admission and previously hospitalized for = 48 hours) or pneumonia in subject who has received chronic dialysis care within 30 days prior to study enrollment
WITH at least two of the following signs and symptoms present within 24 hours of study enrollment in subjects who have not been treated pre-study with an antimicrobial with activity against subject’s MRSA isolate. In subjects that have been treated pre-study with an antimicrobial with activity against subject’s MRSA isolate, symptoms and findings must be present within 24 hours prior to that treatment or within 72 hours prior to enrollment (whichever is closer to the time of enrollment):
• new onset or worsening of cough
• new onset of purulent sputum production or a change (worsening) in character of thesputum or increased respiratory secretions or increased suctioning requirements
• auscultatory findings on pulmonary exam of rales and/or pulmonary consolidation(dullness on percussion, bronchial breath sounds, or egophony)
• dyspnea, tachypnea, or respiratory rate 30/minute, particularly if any or all of theseare progressive in nature
• hypoxemia with a PO2 < 60 mmHg while subject is breathing room air or respiratoryfailure requiring mechanical ventilation in a previously non-ventilated subject
• worsening gas exchange (e.g., O2 desaturations [e.g., Pa O2/Fi O2 240], increasedoxygen requirements, or increased ventilation demand)

Subject must present with the criteria described in 3a or 3b prior to enrollment. Signs and symptoms must have been present within 24 hours of study enrollment in subjects who have not been treated pre-study with an antimicrobial with activity against subject’s MRSA isolate. In subjects that have been treated pre-study with an antimicrobial with activity against subject’s MRSA isolate, symptoms and findings must be present within 24 hours prior to that treatment or within 72 hours prior to enrollment (whichever is closer to the timeof enrollment).
a. At least two of the following:
• Fever defined as body temperature = 38°C (100.4°F) taken orally, = 37.5°C (99.5°F) axillary, or = 38.4°C (101.1°F) taken rectally, typanically via temporal artery or core, or hypothermia defined as body temperature = 35.5°C (96°F) taken orally or = 35.9°C (96°F) taken rectally, tympanically, via temporal artery or core
• Systolic hypotension (systolic blood pressure < 90 mm Hg)
• Temporarily altered mental status consistent with sepsis
• Elevated total peripheral

Exclusion Criteria

Subjects presenting with any of the following will not be included in the trial:
...
Subject with rapidly fatal underlying disease not expected to survive to complete the study.

Subject with high likelihood of death within 72 hours based on multiple organ dysfunction at the time of study enrollment.
...
Subject with known or suspected meningitis, endocarditis, or osteomyelitis.

Subject who has a CD4 cell count < 200 cells/mm3 secondary to HIV infection unless the subject has been on treatment with highly active anti-retroviral therapy (HAART) is on PCP prophylaxis, and clinically and immunologically stable (with CD4 counts from 100-199 and granulocytes = 1000). The subject may be enrolled at the discretion of the investigator after investigator discussion with the medical monitor.

Subject with sustained shock, defined as MAP < 55 mmHg (or if MAP not available, systolic BP < 85 mm Hg) for > 2 hours despite adequate fluid resuscitation and/or sympathomimetic agents to maintain blood pressure.
...
Subject who received linezolid, vancomycin or teicoplanin for greater than 48 hours within the 72 hour period prior to the enrollment. Also excluded are subjects treated for greater than 48 hours with one of the above drugs, and drug began prior to the 72 hour preenrollment period but drug treatment continued into the 72 hour pre-study period. Subject who was treated for the infection under study prior to this timeframe may be enrolled unless the subject received 72 hours or more of treatment and did not respond.

Subject who was treated with a previous antibiotic with MRSA activity against the subject’s isolate (other than linezolid, vancomycin or teicoplanin) for greater than 48 hours within the 72 hour period prior to the enrollment. Also excluded are subjects treated for greater than 48 hours and drug began prior to the 72 hour pre- enrollment period but drug treatment continued into the 72 hour pre-study period. Subjects who received = 72 hours of an antibiotic with activity against the subject’s MRSA isolate (other than linezolid, vancomycin or teicoplanin) for the infection under study and were documented to be a treatment failure may be enrolled. Certain drugs with variable MRSA activity (e.g. fluoroquinolones) may not be excluded if local susceptibility patterns will predict non-susceptibility and is subsequently documented.
...
Subject who has known liver disease (Child-Pugh Class C hepatic insufficiency), or subject with SGPT and/or SGOT > 5 X ULN (upper limit of normal).

Subject who has severe neutropenia (neutrophils < 500 cells/mm3 including segmented cells and bands) unless neutropenia is reversible and count is expected to be >500 cells/ mm3 within 24 hours following first dose of study drug.
...
Subject who is currently on peritoneal dialysis or alternative treatment for renal failure (e.g., hemofiltration, CVVH). Subjects on hemodialysis may be enrolled.
...
Subject in whom his/her weight would require a vancomycin dosing frequency with intervals less than 12 hours if they were randomized to vancomycin, thereby not allowing the blind to be maintained.
...

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified