Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (MK-7655A-016)
Condition: Hospital-Acquired Bacterial Pneumonia; Ventilator-Associated Bacterial Pneumonia
MeSH terms: Pneumonia; Pneumonia, Bacterial
Intervention: IMI/REL FDC; PIP/TAZ FDC; Linezolid
Intervention description: 500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial; 4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial; Open-label 600 mg Linezolid
Intervention MeSH terms: Linezolid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 274.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of a FDC of imipenem/cilastatin (IMI) and
      relebactam (REL) [IMI/REL, MK-7655A] compared to piperacillin/tazobactam (PIP/TAZ) in the
      treatment of adults diagnosed with Hospital-Acquired Bacterial Pneumonia (HABP) or
      Ventilator-Associated Bacterial Pneumonia (VABP). The primary hypothesis is that IMI/REL is
      non-inferior to PIP/TAZ as measured by the incidence rate of all-cause mortality through Day
      28 post-randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Requires treatment with IV antibiotic therapy for HABP or VABP

          -  Fulfills clinical and radiographic criteria within 48 hours prior to randomization,
             with onset of criteria occurring after more than 2 days of hospitalization or within 7
             days after discharge from a hospital for HABP; or at least 2 days after mechanical
             ventilation (for VABP)

          -  Has an adequate baseline (at or within 2 days of screening) lower respiratory tract
             specimen obtained for Gram stain and culture

          -  Has an infection known or thought to be, in the opinion of the investigator, caused by
             microorganisms susceptible to the IV study therapy

          -  Agrees to allow any bacterial isolates obtained from protocol-required specimens
             related to the current infection to be provided to the Central Microbiology Reference
             Laboratory for study-related microbiological testing and long-term storage

          -  Males agree to use contraception as detailed in protocol from the time of providing
             informed consent through completion of the study and refrain from donating sperm
             during this period

          -  Females are not pregnant, not breastfeeding, and are either: a.) Not a woman of
             childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive
             guidance from the time of providing informed consent through completion of the study

          -  If a penicillin skin test is required by local clinical practice, the participant must
             have a negative skin test result for allergy to penicillin

        Exclusion Criteria:

          -  Has a baseline lower respiratory tract specimen Gram stain that shows the presence of
             Gram-positive cocci only

          -  Has confirmed or suspected community-acquired bacterial pneumonia (CABP)

          -  Has confirmed or suspected pneumonia caused by Mycoplasma, Chlamydia, or Legionella,
             or of viral, fungal, or parasitic etiology

          -  Has HABP/VABP caused by an obstructive process, including lung cancer (or other
             malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known
             obstruction

          -  Has a carcinoid tumor or carcinoid syndrome

          -  Has active immunosuppression

          -  Is expected to die during the 7- to 14-day treatment period, despite adequate
             antibiotic therapy

          -  Has a concurrent condition or infection that, in the investigator's judgment, would
             preclude evaluation of therapeutic response

          -  Has a history of serious allergy, hypersensitivity, or any serious reaction to any
             β-lactams or β-lactamase inhibitors

          -  Has a history of a seizure disorder which has required ongoing treatment with
             anticonvulsive therapy or prior treatment with anti-convulsive therapy within the last
             3 years

          -  Is currently undergoing hemodialysis or peritoneal dialysis

          -  A WOCBP who has a positive urine pregnancy test at screening

          -  Has received effective antibacterial drug therapy with known coverage of pathogens
             that cause HABP/VABP for a continuous duration of more than 48 hours during the
             previous 72 hours

          -  Is anticipated to be treated with any of the prohibited medications during the course
             of study therapy

          -  Is currently participating in, or has participated in, any other clinical study
             involving the administration of investigational or experimental medication (not
             licensed by regulatory agencies) at the time of the presentation or during the
             previous 90 days prior to screening or is anticipated to participate in such a
             clinical study during the course of this trial

          -  Has previously participated in this study at any time