Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam

Phase 1

• Conditions: Ventilated Nosocomial Pneumonia; MedDRA version: 20.1Level: LLTClassification code 10052596Term: Nosocomial pneumoniaSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2012-002862-11-CZ
• Lead Sponsor: Cubist Pharmaceuticals LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-09
• Last Update Posted: 20 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 726

Inclusion Criteria

To be eligible for enrollment, a subject must satisfy all of the following entry 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 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 HABP:
• At least 1 of the following signs and/or symptoms must be present
within the 24 hours prior to intubation OR within the 48 hours after intubation in a patient who has been either hospitalized for =48 hours or who has 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/FiO2 ratio)
For VABP:
Receiving mechanical ventilation =48 hours and at least one of the following:
• 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
• Hypoxemia defined as an arterial blood gas partial pressure of oxygen less than 60 mmHg while the subject is breathing room air (or FiO2 equivalent), OR a pulse oximetry oxygen saturation less than 90% while the subject is breathing room air (or FiO2 equivalent), OR worsening PaO2/FiO2.
4. Chest radiograph obtained within the 24 hours prior to the first dose of study drug shows the presence of new or pr

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 therapeutic 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 (ie, 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
3. Received systemic or inhaled antibiotic therapy effective against
Gram-negative
pathogens that cause VNP, for >24 hours in the 72 hours prior to the
first dose of study drug.
Drugs with only Gram-positive activity [eg, daptomycin, vancomycin,
linezolid] are
allowed.
Exceptions:
•?Persistent/worsening signs and/or symptoms of VNP are still present
despite
=48 hours of antibiotic therapy for the treatment of the current VNP, and
(a) a
LRT culture obtained while the subject is on the failing antibiotic therapy
for this episode of VNP showed growth of a Gram-negative pathogen and
(b) the
isolated pathogen is not known to be resistant to one of the study drugs.
•?Signs and/or symptoms of VNP develop after receiving =48 hours of prior antibacterial therapy for an indication other than the current VNP. NOTE: Subjects on =48 hours of antibiotics for infection prophylaxis (rather than treatment of a documented or suspected infection) are not eligible for enrollment under this exception
•?Treatment with a non-absorbed antibiotic used for gut
decontamination (eg,
low-dose erythromycin) or to eradicate C. difficile.
4. Baseline Gram stain shows the presence of only Gram-positive
bacteria.
Exception: If the subject has a lower respiratory tract culture growing a
Gramnegative
pathogen obtained within 72 hours prior to the first dose of study drug,
these
results will supersede baseline Gram stain results of only Gram-positive
bacteria.
5. Active immunosuppression, including human immunodeficiency virus
(HIV) with a
known CD4 count of <200 cells/mm3, active hematological malignancy,
recipients of
solid organ or bone marrow transplants, subjects currently on
immunosuppressive
therapy including cancer chemotherapy, medications for prevention of
transplant
rejection, or chronic administration of corticosteroids (defined as >40
mg of prednisone
per day administered continuously for more than 14 days prior to the
first dose of study
drug);
6. Receipt of >24 hours of a carbapenem within 7 days prior to the first
dose of study drug;
7. Growth of a meropenem-resistant or ceftolozane/tazobactamresistant,
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 CLCR <15
mL/min, OR requirement
for peritoneal or hemo-dialysis or hemofiltration, OR a urine output <20
mL/hour over a
24-hour

Study & Design

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