Clinical Trials List
Protocol NumberTR701-132
2014-02-14 - 2020-08-28
Phase III
Terminated4
Study ended1
ICD-10J15.6
Pneumonia due to other aerobic Gram-negative bacteria
ICD-9482.83
Pneumonia due to other gram-negative bacteria
A Phase 3 Randomized Double-blind Study Comparing TR-701 FA and Linezolid in Ventilated Gram-positive Nosocomial Pneumonia
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Sponsor
Trius Therapeutics, a Wholly Owned Subsidiary of Cubist Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/19
Investigators and Locations
Co-Principal Investigator
- 曾敬閔 Division of Thoracic Medicine
- Kang-Cheng Su Division of Thoracic Medicine
- Wei-Zhi Chen Division of Thoracic Medicine
- Hsin-Kuo Ko Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Pin-Kuei Fu Division of Thoracic Medicine
- Chien-Hua Tseng Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 林裕清 Division of General Internal Medicine
- 洪明賜 Division of General Internal Medicine
- 黃舒儀 Division of General Internal Medicine
- 林進國 Division of General Internal Medicine
- 林玠模 Division of General Internal Medicine
- 楊聰明 Division of General Internal Medicine
- 周育廷 Division of General Internal Medicine
- Ying-Huang Tsai Division of General Internal Medicine
- 周晏立 Division of General Internal Medicine
- 莊閔鈞 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 梁信杰 Division of Thoracic Medicine
- 田霓 Division of Thoracic Medicine
- Yu-Chao Lin Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
2 Study ended
Condition/Disease
Ventilated Gram-positive Nosocomial Pneumonia
Objectives
The primary objective is to determine the noninferiority (NI) in all-cause mortality
(ACM) within 28 days after randomization of intravenous (IV) TR-701 FA compared
with IV linezolid in the Intent to Treat (ITT) Analysis Set in ventilated patients with
presumed gram-positive hospital-acquired bacterial pneumonia (HABP) or grampositive ventilator-associated bacterial pneumonia (VABP), collectively defined as
ventilated nosocomial pneumonia (VNP).
Secondary objectives:
• To compare the ACM observed with TR-701 FA and linezolid within 28 days
after randomization in the microbiological ITT (Micro-ITT) Analysis Set
• To compare Investigator’s assessment of clinical response for TR-701 FA and
linezolid treatment at the Test of Cure (TOC) Visit in the ITT and Clinically
Evaluable (CE) Analysis Sets (European Medicines Agency [EMA] primary
endpoint)
• To evaluate the safety profile of TR-701 FA and compare with that of
linezolid
• To assess the population pharmacokinetic (PK) and PK/pharmacodynamic
(PD) profile of TR-700
Test Drug
TR-701 FA for Injection
Active Ingredient
Tedizolid phosphate
Dosage Form
vial
Dosage
200
Endpoints
The primary outcome is ACM within 28 days after randomization in the ITT Analysis
Set.
Secondary outcomes include the following:
• ACM within 28 days after randomization (Micro-ITT Analysis Set)
• Investigator’s assessment of clinical response rates at the TOC Visit (ITT and
CE Analysis Sets)
• ACM in patients with or methicillin-susceptible Staphylococcus aureus
(MSSA) or MRSA (ITT Analysis Set)
• Clinical response by Investigator in patients with MSSA or MRSA (ITT and
Microbiologically Evaluable (ME)-2 Analysis Sets)
Set.
Secondary outcomes include the following:
• ACM within 28 days after randomization (Micro-ITT Analysis Set)
• Investigator’s assessment of clinical response rates at the TOC Visit (ITT and
CE Analysis Sets)
• ACM in patients with or methicillin-susceptible Staphylococcus aureus
(MSSA) or MRSA (ITT Analysis Set)
• Clinical response by Investigator in patients with MSSA or MRSA (ITT and
Microbiologically Evaluable (ME)-2 Analysis Sets)
Inclution Criteria
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 gramnegative bacteria) OR
• Culture from sample obtained within 72 hours prior to randomization
positive for methicillin-resistant Staphylococcus aureus (MRSA)
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 gramnegative bacteria) OR
• Culture from sample obtained within 72 hours prior to randomization
positive for methicillin-resistant Staphylococcus aureus (MRSA)
Exclusion Criteria
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 as severe
limitations - experiences symptoms even while at rest, mostly bedbound
patients, within 1 year
17. Stroke or subarachnoid hemorrhage within 5 days prior to randomization
18. Patients with uncontrolled hypertension, pheochromocytoma, carcinoid
syndrome, or thyrotoxicosis
19. Treatment with investigational medicinal product ≤30 days before the first
infusion of study drug
20. Investigational device present, or removed <30 days before the first infusion of
study drug or presence of device-related infection
21. Hypersensitivity to oxazolidinones (eg, linezolid) or any component in the
formulation
22. Women who are pregnant or nursing, or who are of childbearing potential and
unwilling to use an acceptable method of birth control (eg, intrauterine device,
double-barrier method [eg, condoms, diaphragm, or cervical cap with
spermicidal foam, cream or gel], or male partner sterilization (excluding
women ≥2 years postmenopausal or surgically sterile)
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 as severe
limitations - experiences symptoms even while at rest, mostly bedbound
patients, within 1 year
17. Stroke or subarachnoid hemorrhage within 5 days prior to randomization
18. Patients with uncontrolled hypertension, pheochromocytoma, carcinoid
syndrome, or thyrotoxicosis
19. Treatment with investigational medicinal product ≤30 days before the first
infusion of study drug
20. Investigational device present, or removed <30 days before the first infusion of
study drug or presence of device-related infection
21. Hypersensitivity to oxazolidinones (eg, linezolid) or any component in the
formulation
22. Women who are pregnant or nursing, or who are of childbearing potential and
unwilling to use an acceptable method of birth control (eg, intrauterine device,
double-barrier method [eg, condoms, diaphragm, or cervical cap with
spermicidal foam, cream or gel], or male partner sterilization (excluding
women ≥2 years postmenopausal or surgically sterile)
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
726 participants
