Safety and Efficacy Study of Ceftolozane/Tazobactam to Treat Ventilated Nosocomial Pneumonia (MK-7625A-008)
Condition: Healthcare-Associated Pneumonia; Ventilator-Associated Pneumonia; Lung Diseases
MeSH terms: Pneumonia; Pneumonia, Ventilator-Associated; Healthcare-Associated Pneumonia; Lung Diseases
Intervention: Ceftolozane/tazobactam; Meropenem
Intervention description: Ceftolozane/tazobactam is an antibacterial consisting of a co-formulation of ceftolozane, a novel antipseudomonal cephalosporin and tazobactam, a well-established beta (β)-lactamase inhibitor (BLI) being developed for the treatment of serious bacterial infections.; Meropenem is a broad spectrum injectable antibiotic widely used to treat serious infections such as ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia.
Intervention MeSH terms: Meropenem; Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 726.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 3, multicenter, prospective, randomized study of intravenous (IV)
      ceftolozane/tazobactam versus IV meropenem in the treatment of adult participants with either
      ventilator-associated bacterial pneumonia (VABP) or ventilated hospital-acquired bacterial
      pneumonia (HABP). The primary objective is to demonstrate the non-inferiority of
      ceftolozane/tazobactam versus meropenem in adult participants with ventilated nosocomial
      pneumonia (VNP) based on the difference in Day 28 all-cause mortality rates in the
      Intent-to-treat (ITT) population using a non-inferiority margin of 10%.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Adult participants diagnosed with either VABP or ventilated HABP requiring IV
             antibiotic therapy;

          -  Intubated and on mechanical ventilation at the time of randomization;

          -  New or progressive infiltrate on chest radiography consistent with pneumonia;

          -  Presence of clinical criteria consistent with a diagnosis of ventilated nosocomial
             pneumonia.

        Key Exclusion Criteria:

          -  History of moderate or severe hypersensitivity reactions to beta-lactam antibiotics;

          -  Prior non-study antibiotics for > 24 hours;

          -  Gram stain of lower respiratory tract specimen showing only gram positive bacteria;

          -  Active immunosuppression;

          -  End-stage renal disease or requirement for dialysis;

          -  Expected survival < 72 hours;

          -  Severe confounding respiratory condition (i.e., chest trauma with paradoxical
             respiration);

          -  Known or suspected community-acquired bacterial pneumonia.

          -  Anticipated concomitant use of any of the following medications during the course of
             study therapy: valproic acid or divalproex sodium. Anticipated concomitant use of
             serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin 5-HT1 receptor
             agonists (triptans), meperidine, or buspirone during the course of linezolid
             treatment.

          -  Receipt of a monoamine oxidase inhibitor within 14 days prior to the first dose of
             study drug or anticipated concomitant use during the course of linezolid therapy.