None listed
Conditions
Interventions
Drug : Subjects will be randomized 1:1 to receive either ceftolozane/tazobactam 3000 mg every 8 hours by Intravenous infusion or meropenem 1000 mg every 8 hours by Intravenous infusion. The duration o
however, treatment may be extended up to 14 days only in subjects with P. aeruginosa isolated from the baseline respiratory culture.
Sponsors
INC Research South Korea
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent prior to any study-related procedure not part of normal medical care. If the subject is unable to do so, local country laws and institution specific guidelines and requirements in place for obtaining informed consent should be met. A legally acceptable representative may provide consent, provided this is approved by local country and institution specific guidelines. If a subject comes to consciousness while still in the study and per the Investigator’s judgment the subject is able to read, assess, understand, and make his/her own decision to participate in the trial, the subject can agree to continue study participation and the subject may be re-consented, if required by local country and institution specific guidelines; 2. Be males or females aged 18 years or older; If female, subject must not be pregnant or nursing, and is either: • Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or • Of childbearing potential and meets at least 1 of the following: ? Is practicing an effective method of contraception (eg, oral/parenteral contraceptives plus barrier method), or ? Has a vasectomized partner, or ? Is currently abstinent from sexual intercourse. Subjects must be willing to practice the chosen contraceptive method or remain abstinent during the conduct of the study and for at least 35 days after last dose of study medication. Non-vasectomized males are required to practice effective birth control methods (eg, abstinence, use of condom, or use of other barrier device) during the treatment period and for at least 35 days after last dose of study medication; 3. Intubated (via endotracheal tube, including tracheostomy patients) and on mechanical ventilation at the time of randomization: For ventilated Hospital-acquired bacterial pneumonia: • At least 1 of the following signs or symptoms within 24 hours prior to intubation OR within the 48 hours after intubation of a patient hospitalized for =48 hours or have been discharged from a hospital within the prior 7 days (includes patients institutionalized in skilled nursing or other long-term care facility): ? A new onset of cough (or worsening of baseline cough) ? Dyspnea, tachypnea, or respiratory rate greater than 30 per minute, particularly if any or all of these signs or symptoms are progressive in nature ? Hypoxemia defined as an arterial blood gas partial pressure of oxygen less than 60 mmHg while the subject is breathing room air, OR a pulse oximetry oxygen saturation less than 90% while the subject is breathing room air, OR worsening of the ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2ratio). For VABP, receiving mechanical ventilation =48 hours: • Acute changes made in the ventilator support system to enhance oxygenation, as determined by worsening partial pressure of oxygen on arterial blood gas, or worsening PaO2/FiO2 4. Chest radiograph shows the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia (based on Investigator evaluation or report from a qualified medical professional who is not the investigator). A computed tomography (CT) scan may be used in place of a chest X-ray, as appropriate (eg, in subjects with blunt trauma to the chest wall); 5. Have the following clinical criteria within the 24 hours prior to the first dose of study drug: • Purulent tra
Exclusion criteria
Exclusion criteria: 1. Any of the following diagnoses or conditions that interfere with the assessment or interpretation of outcome: • Atypical, viral, or fungal (including Pneumocystis jiroveci), known or suspected community-acquired bacterial pneumonia • Tracheobronchitis (without documented pneumonia), chemical pneumonitis, or postobstructive pneumonia • Active primary or metastatic lung cancer • Pleural effusions (or empyema) requiring drainage, lung abscess, or bronchiectasis • Cystic fibrosis, acute exacerbation of chronic bronchitis, or active pulmonary tuberculosis • New York Heart Association (NYHA) Stage IV Congestive Heart Failure or Cirrhotic Liver Disease • Full thickness burns (greater than 15% of total body surface area) • Severe confounding respiratory condition due to penetrating chest trauma (i.e., chest trauma with paradoxical respiration) 2. Has a documented history of any moderate or severe hypersensitivity (or allergic) reaction to any ß-lactam antibacterial; Note: A history of a rash while on a ß-lactam antibiotic does not automatically exclude a subject (eg, a subject with history of a mild rash followed by uneventful re exposure may be considered for enrollment) 3. Received systemic or inhaled antibiotic therapy, effective against Gram-negative pathogens that cause Ventilated nosocomial pneumonia, regardless of the indication, for >24 hours (i.e., >1 dose of a once daily antibiotic, >2 doses of a twice daily antibiotic, etc.) in the last 72 hours. Exceptions: • Signs and/or symptoms of Ventilated nosocomial pneumonia are still present despite >48 hours on the prior antibacterial regimen for this episode of VNP, provided prior respiratory or blood culture did not grow a meropenem-resistant Gram-negative pathogen, or only S. aureus (methicillin-susceptible S. aureus [MSSA] or methicillin-resistant S. aureus [MRSA]). Requires microbiological confirmation of a Gram-negative pathogen. • Prior therapy with a non-absorbed antibiotic therapy used for gut decontamination (example, low-dose erythromycin) or to eradicate C. difficile. 4. Gram stain performed within 36 hours prior to randomization shows presence of only Gram-positive bacteria. Note: Endotracheal aspirate specimens with an average of >10 SECs and 40 mg of prednisone per day administered continuously for more than 14 days prior to randomization); Note: Subjects infected with the human immunodeficiency virus (HIV) but who do not have Acquired Immune Deficiency Syndrome, may be considered for enrollment. 6. Receipt of imipenem/cilastatin, meropenem, or doripenem within 15 days prior to the first dose of study drug; 7. Growth of an meropenem-resistant, Gram-negative pathogen from a respiratory or blood culture, within 15 days prior to the first dose of study drug; 8. Development of end-stage renal disease defined as a Creatinine clearance <15 mL/min, OR requirement for peritoneal or hemo-dialysis or hemofiltration, OR a urine output < 20 mL/hour o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Day 28 all-cause mortality in the Intent- to-Treat population | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical response at the Test-of-cures visit in the Intent to Treat population;Clinical response at the Test-of-cures visit in the Clinically Evaluable population;Clinical response for subjects at the Test-of-cures visit in the subset of subjects who had P. aeruginosa isolated from the baseline LRT culture in the Microbiological Intent to Treat population.;Day 28 all-cause mortality in the Microbiological Intent to Treat population | — |
Countries
Korea, Republic of
Contacts
Public ContactSungA Kim
Seoul National University Hospital
Outcome results
None listed