Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)
Condition: Bacterial Pneumonia
MeSH terms: Pneumonia; Pneumonia, Bacterial
Intervention: Imipenem; Relebactam; Cilastatin; Piperacillin; Tazobactam; Linezolid
Intervention description: Imipenem 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days; Relebactam 250 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days; Cilastatin 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days; Piperacillin 4000 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days; Tazobactam 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days; Linezolid 600 mg administered open-label by IV every 12 hours for up to 14 days
Intervention MeSH terms: Tazobactam; Linezolid; Piperacillin; Imipenem; Relebactam; Cilastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 537.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study aims to compare treatment with a fixed-dose combination (FDC) of
      imipenem/relebactam/cilastatin (IMI/REL) with a FDC of piperacillin/tazobactam (PIP/TAZ) in
      participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or
      VAPB, respectively). The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ in the
      incidence rate of all-cause mortality.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Requires treatment with IV antibiotic therapy for hospital-acquired bacterial
             pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)

          -  Fulfills clinical and radiographic criteria, with onset of criteria occurring after
             more than 48 hours of hospitalization or within 7 days after discharge from a hospital
             (for HABP); or at least 48 hours after mechanical ventilation (for VABP)

          -  Has an adequate baseline lower respiratory tract specimen obtained for Gram stain and
             culture

          -  Has an infection known or thought to be 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, long term storage, and other
             future testing

          -  Is not of reproductive potential; or if of reproductive potential agrees to avoid
             impregnating a partner or avoid becoming pregnant, by practicing abstinence or using
             acceptable contraception

        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 of viral, fungal or parasitic origin

          -  Has HABP/VABP caused by an obstructive process, including lung cancer or other known
             obstruction

          -  Has a carcinoid tumor or carcinoid syndrome

          -  Has active immunosuppression defined as either receiving immunosuppressive medications
             or having a medical condition associated with immunodeficiency

          -  Is expected to survive for less than 72 hours

          -  Has a concurrent condition or infection that would preclude evaluation of therapeutic
             response

          -  Has received effective antibacterial drug therapy for the index infection of HABP/VABP
             for more than 24 hours continuously, during the previous 72 hours

          -  Has a history of serious allergy, hypersensitivity or a serious reaction to any
             penicillin or beta-lactamase inhibitors

          -  Female is pregnant, expecting to conceive, is breastfeeding or plans to breastfeed

          -  Has a history of seizure disorder requiring ongoing prior treatment with
             anti-convulsive therapy within the last 3 years

          -  Anticipates treatment with the following: valproic acid or divalproex sodium,
             serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin receptor
             antagonists, meperidine, buspirone, concomitant systemic antibacterial agents,
             antifungal or antiviral therapy for the index infection of HABP/VABP

          -  Is currently undergoing hemodialysis or peritoneal dialysis

          -  Is currently participating in, has participated in during the previous 30 days, or
             anticipates to participate in any other clinical study involving the administration of
             experimental medication

          -  Has previously participated in this study