Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014)

A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Subjects With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia

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.

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