Pneumonia, Ventilator-Associated
Conditions
Brief summary
Ventilator-associated pneumonia (VAP) is a commonplace complication of intensive care patients ventilated for longer than 48 hours. Methicillin-resistant Staphylococcus aureus (MRSA) is the cause of late onset VAP in up to about 30% of cases in US hospitals. Ineffective treatment of MRSA VAP clearly leads to prolonged mechanical ventilation and is probably associated with higher mortality. The purpose of this protocol is to directly compare linezolid and vancomycin specifically for MRSA VAP.
Interventions
DRUGVancomycin
1 gram IV every 12 hours for 7 to 14 days
DRUGLinezolid
600 mg every 12 hours (intravenously \[IV\] for a minimum of the first 4 days followed by a switch to oral if tolerated by patient) for a total duration of 7 to 14 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient must have or be suspected of having a ventilator-associated pneumonia (VAP) due to MRSA. * Patient must be hospitalized for at least 5 days, must be ventilator-dependent ≥ 48 hours prior to screen/baseline, and anticipated to remain on the ventilator for 72 hours after enrollment so follow-up BAL can be performed. * Clinical picture compatible with pneumonia (acquired during ventilation) * Chest X Ray at baseline/screen or within 24 hours of initiation of therapy must be consistent with diagnosis of pneumonia
Exclusion criteria
* Hypersensitivity to linezolid, vancomycin, or one of the excipients in any of these drug formulations. * Infections due to gram-positive organisms known to be resistant to either of the study drugs. * Any antibiotic used in the treatment of MRSA, such as vancomycin, TMP/SMX, rifampin, or linezolid, for more than 48 hours prior to patient's enrollment into the study. * Patients with neutropenia, AIDS, lymphoma or anticipated chemotherapy. * Patients who have long-term tracheostomy (for more than 60 days). Acute tracheostomy patients are allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess early microbiologic response in patients with VAP due to MRSA based on semi-quantitative culture of bronchoscopic bronchoalveolar lavage (BAL) in patients treated with linezolid vs vancomycin. | 72-96 hours |
Secondary
| Measure | Time frame |
|---|---|
| To compare duration of mechanical ventilation | 0000 |
| To compare post treatment tracheal colonization | FU: 14 days after EOT +/- 2 days |
| To identify clinical correlates of infection based on microbiologic sampling as determined by original and modified CPIS (Clinical Pulmonary Infection Score) | EOT: Day 14; FU: 14 days after EOT +/- 2 days |
| To compare the microbiological cure based on BAL specimens with the traditional criteria for microbiologic cure | 72-96 hours |
| To compare mortality at End Of Treatment (EOT) and Follow up (FU); To compare clinical outcome at EOT and FU | EOT: Day 14; FU: 14 days after EOT +/- 2 days |
Countries
Puerto Rico, United States
Outcome results
None listed