The purpose of this study is to learn if an experimental antibiotic called TR-701 FA can safely and effectively treat ventilated patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia. The experimental antibiotic will be tested against the already approved antibiotic Linezolid. The sponsor of the study wants to prove, that the new medication isn't inferior regarding efficacy and safety as compared to the already approved medication Linezolid.
- Conditions
- Ventilated Gram-positive nosocomial pneumoniaMedDRA version: 16.1Level: LLTClassification code 10052596Term: Nosocomial pneumoniaSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2013-004154-22-ES
- Lead Sponsor
- Trius Therapeutics, a Wholly Owned Subsidiary of Cubist Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 726
Patients who meet all the following diagnostic and inclusion criteria are eligible for the study.
1. Males or females ? 18 years old
2. Adequate venous access for IV study drug administration
3. Intubated (via endotracheal tube, including tracheostomy patients) and mechanically ventilated, AND
? For HABP, at least 1 of the following signs or symptoms presenting within 24 hours prior to intubation of a patient hospitalized, including patients institutionalized in long-term care facilities, for ?48 hours. If the patient has been discharged, discharge must have been within 7 days:
o A new onset of cough (or worsening of baseline cough)
o Dyspnea, tachypnea, or respiratory rate >30/minute, particularly if any or all of these signs or symptoms are progressive in nature
o Hypoxemia (eg, a partial pressure of oxygen <60 mm Hg while the patient is breathing on room air as determined by arterial blood gas (ABG) or oxygen saturation <90% while the patient is breathing on room air as determined by pulse oximetry, or worsening (decline from any earlier finding) of the ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2), or respiratory failure requiring mechanical ventilation
? For VABP, receiving mechanical ventilation ?48 hours:
Acute changes made in the ventilator support system to enhance oxygenation, as determined by ABG, or worsening PaO2/FiO2
4. Chest radiograph shows the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia (based on Investigator evaluation; report from qualified medical professional who is not the Investigator to be provided)
5. Clinical findings to support diagnosis of HABP/VABP
? New onset of suctioned respiratory secretions characterized by purulent appearance indicative of bacterial pneumonia
? And at least 1 of the following:
o Documented fever (oral or tympanic ?38°C [100.4°F] or a core temperature ?38.3°C [101°F]) OR
o Hypothermia (core body temperature ?35°C [95.2°F]) OR
o Total peripheral white blood cell (WBC) count ?10,000 cells/mm3 OR
o Leukopenia with total WBC ?4500 cells/mm3 OR
o ?15% immature neutrophils (bands)
6. Acute Physiology and Chronic Health Evaluation (APACHE II) score ?15
7. High probability of pneumonia caused by gram-positive cocci only or in a mixed infection defined as follows:
Respiratory Sample
? Gram stain performed within 24 hours prior to randomization using an acceptable purulent respiratory specimen such as sputum or endotracheal aspirate sample with <10 squamous epithelial cells (SEC) per low-power field and more than 25 polymorphonuclear cells per low-power field showing gram-positive bacteria (with or without gram-negative bacteria)
OR
? Gram stain performed within 24 hours prior to randomization using an acceptable respiratory specimen such as protected brush specimen, bronchoalveolar lavage (BAL), mini BAL, or sample from an exudative pleural effusion showing gram-positive bacteria (with or without gram-negative bacteria)
OR
? Culture from sample obtained within 72 hours prior to randomization positive for methicillin-resistant Staphylococcus aureus (MRSA)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 544
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 182
Patients who meet any of the following criteria are not eligible to participate in this study:
1. Known or suspected community-acquired bacterial pneumonia or viral, fungal, or parasitic pneumonia
2. Any of the following health conditions:
? Legionella infection (Legionella pneumophila pneumonia)
? Cystic fibrosis
? Bronchiectasis
? Human immunodeficiency virus (HIV) infection with CD4 count <200 cell/mm³ (HIV testing is not required)
? Known or suspected Pneumocystitis jiroveci pneumonia
? Known or suspected active tuberculosis
? Lung abscess
? Empyema
? Evidence of endocarditis
? Tracheobronchitis
3. Received systemic or inhaled antibiotic therapy effective for gram-positive pathogens that cause VNP for >24 hours (for example, >1 dose of a once-daily antibiotic, >2 doses of a twice daily antibiotic) in the last 72 hours
EXCEPTIONS
? Progression of disease on the prior antibacterial regimen for this episode of VNP after >48 hours of treatment; requires microbiological confirmation of a gram-positive pathogen,
OR
? Patient developed symptoms of pneumonia and a new infiltrate while receiving the prior antibacterial regimen for reasons other than the current VNP,
OR
? Patient received systemic antibacterial therapy that does not cover the gram positive pathogen isolated on respiratory culture,
OR
? Antibiotic therapy for gut decontamination (example, low-dose erythromycin) or C. difficile infection
4. Receipt of monoamine oxidase A and B inhibitors (see Appendix 1) from 2 weeks prior to randomization or planned use through the End of Therapy (EOT) Visit
5. Planned use of agents with serotonergic activity (see Appendix 1 and Section 1.4) through the EOT Visit
6. Administration of linezolid ?30 days before the first infusion of study drug, except for receipt of a single administration, within 24 hours prior to the first dose of study drug, to treat the current VNP
7. Bronchial obstruction or a history of postobstructive pneumonia (this does not exclude patients with pneumonia who have underlying chronic obstructive pulmonary disease)
8. Primary lung cancer or another malignancy metastatic to the lungs
9. Recent opportunistic infections where the underlying cause of the infection is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome)
10. Expected survival <72 hours or any 1 of the following:
? A Do Not Resuscitate order
? Acute respiratory distress syndrome/acute lung injury secondary to septic shock, or due to third degree burns or inhalation injury
? Nonresolving pulmonary edema secondary to congestive heart failure
11. Severe confounding respiratory condition due to penetrating chest trauma or chest trauma with paradoxical respiration
12. Burns >40% of total body surface area
13. Current or anticipated neutropenia with absolute neutrophil count <500 cells/mm3
14. Severe renal disease requiring peritoneal dialysis, venovenous dialysis, or other forms of renal filtration. Patients with severe renal disease on hemodialysis may be enrolled
15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ??10× upper limit of normal OR severe hepatic disease with Child Pugh score >9
16. Investigator?s opinion of clinically significant electrocardiogram (ECG) finding such as ischemia, infarct, or ventricular arrhythmia with immediate potential for a fatal outcome, or, prior to the current infection, a history of New York Heart Association Class IV cardiac failure defined
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method