Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Participants With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (MK-7655A-016)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Hospital-Acquired Bacterial Pneumonia; Ventilator-Associated Bacterial Pneumonia

Treatments: Drug: IMI/REL FDC; Drug: Linezolid; Drug: PIP/TAZ FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT03583333

MK-7655A-016 (Other Identifier)

7655A-016

PHRR190814-002177 (Registry Identifier)

2018-003202-82 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 274 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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274 participants in 2 patient groups

IMI/REL FDC

Experimental group

Description:

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.

Treatment:

Drug: Linezolid

Drug: IMI/REL FDC

PIP/TAZ FDC

Active Comparator group

Description:

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.

Treatment:

Drug: PIP/TAZ FDC

Drug: Linezolid