Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (MK-7655A-016)
Hospital-Acquired Bacterial Pneumonia, Ventilator-Associated Bacterial Pneumonia
About this trial
This is an interventional treatment trial for Hospital-Acquired Bacterial Pneumonia
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
Sites / Locations
- Santa Casa de Misericordia de Belo Horizonte ( Site 0300)
- Hospital de Base de Sao Jose de Rio Preto ( Site 0301)
- Beijing Chaoyang Hospital ( Site 0126)
- Peking University First Hospital ( Site 0131)
- Aero Space center hospital ( Site 0118)
- The Seventh Medical Center of PLA General Hospital-Intensive medicine ( Site 0157)
- Peking University Third Hospital ( Site 0115)
- Beijing Hospital ( Site 0127)
- The First Affiliated Hospital Of Fujian Medical University-Respiratory ( Site 0136)
- Zhongshan Hospital Affiliated to Xiamen University ( Site 0133)
- Zhangzhou Municipal Hospital of Fujian Province-Neurosurgery Department ( Site 0150)
- The First Affiliated Hospital ( Site 0100)
- The First Affiliated Hospital of Guangzhou Medical University ( Site 0123)
- Guangzhou First People's Hospital ( Site 0101)
- Zhujiang Hospital of Southern Medical University ( Site 0148)
- Southern Medical University Nanfang Hospital ( Site 0120)
- Huizhou Municipal Central Hospital ( Site 0140)
- Shenzhen People s Hospital ( Site 0134)
- The first people s hospital of Nanning ( Site 0138)
- The first people s hospital of Nanning ( Site 0141)
- Hainan General Hospital ( Site 0106)
- The First Affiliated Hospital of Zhengzhou University ( Site 0121)
- Shiyan City People's Hospital-Neurosurgery ( Site 0155)
- Changsha Central Hospital ( Site 0119)
- Hunan Provincial People Hospital ( Site 0122)
- The First People's Hospital of Changzhou ( Site 0139)
- First Huai'an Hospital Affiliated to Nanjing Medical University-Neurosurgery Department ( Site 0153)
- First Hospital Affiliated to Suzhou University ( Site 0111)
- Wuxi People's Hospital ( Site 0124)
- Affiliated Hospital of Jiangsu University ( Site 0147)
- Jiangxi Provincial People's Hospital ( Site 0129)
- The First Affiliated Hospital of Nanchang University ( Site 0132)
- The Second Affiliated Hospital of Nanchang University-Neurosurgery Department ( Site 0151)
- The First Affiliated Hospital of China Medical University ( Site 0116)
- General Hospital of Ningxia Medical University ( Site 0135)
- People's Hospital of Liaocheng City-Neurology ( Site 0154)
- Ruijin Hospital Shanghai Jiao Tong University School of Medicine ( Site 0104)
- Huadong Hospital Affiliated Fudan University ( Site 0103)
- Huashan Hospital of Fudan University ( Site 0105)
- Shanghai General Hospital ( Site 0125)
- Shanghai Pulmonary Hospital ( Site 0108)
- Tianjin Medical University General Hospital ( Site 0113)
- The First Affiliated Hospital.Zhejiang University ( Site 0102)
- Sir Run Run Shaw Hospital School of Medicine Zhejiang University ( Site 0110)
- People s Hospital of Lishui City ( Site 0137)
- Ningbo First Hospital-neurosurgery ( Site 0152)
- The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0130)
- Hopital Roger Salengro du Lille ( Site 0601)
- CHU de Nantes - Hotel Dieu ( Site 0600)
- Hospices Civils de Lyon ( Site 0603)
- Hopital Bicetre ( Site 0605)
- Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0800)
- Hospital Civil Nuevo de Guadalajara Dr. Juan I. Menchaca ( Site 0804)
- Mary Johnston Hospital ( Site 0901)
- Lung Center of the Philippines ( Site 0903)
- West Visayas State University Medical Center ( Site 0900)
- Spitalul Clinic Judetean de Urgenta Pius Branzeu ( Site 1103)
- Spitalul Clinic de Urgenta Bagdasar-Arseni ( Site 1101)
- First City Clinical Hospital n.a. E.E.Volosevich ( Site 1016)
- City Hospital #2 Severodvinsk ( Site 1017)
- Research Institute of Emergency Medicine n.a. I.I.Dzhanelidze ( Site 1011)
- Clinical Hospital #122 L.G. Sokolova FMBA ( Site 1015)
- City Hospital #26 ( Site 1002)
- ME Dnipropetrovsk Clinical Joinder of Emergency Care of DRC ( Site 1304)
- Ivano-Frankivsk regional clinical hospital ( Site 1301)
- City Clinical Hospital No13 of Kharkiv City Council ( Site 1303)
- Kiyv city municipal hospital 17 ( Site 1300)
- Reg. Clin. Hospital ( Site 1306)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
IMI/REL FDC
PIP/TAZ FDC
Imipenem/cilastatin/relebactam (IMI/REL) administered intravenously (IV) as a fixed-dose combination (FDC) at a dosage of 500 mg IMI/250 mg REL, once every 6 hours for a minimum 7 days, up to 14 days. At the start of IMI/REL treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.
Piperacillin/tazobactam (PIP/TAZ ) administered IV as a FDC at a dosage of 4000 mg PIP/500 mg TAZ once every 6 hours for a minimum 7 days, up to 14 days. At the start of PIP/TAZ treatment, participants will be treated empirically with 600 mg open-label linezolid administered IV every 12 hours until methicillin-resistant Staphylococcus aureus (MRSA) is ruled out. Participants with confirmed MRSA infection will continue to receive 600 mg linezolid every 12 hours for a minimum of 7 days, up to 14 days total.