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

Merck Sharp & Dohme LLC274 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

274

Conditions

Hospital-Acquired Bacterial Pneumonia Ventilator-Associated Bacterial Pneumonia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Locations (68)

Santa Casa de Misericordia de Belo Horizonte ( Site 0300)

Belo Horizonte, Minas Gerais, Brazil

Hospital de Base de Sao Jose de Rio Preto ( Site 0301)

Sao Jose Do Rio Preto - SP, São Paulo, Brazil

Beijing Chaoyang Hospital ( Site 0126)

Beijing, Beijing Municipality, China

Peking University First Hospital ( Site 0131)

Beijing, Beijing Municipality, China

Aero Space center hospital ( Site 0118)

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

Percentage of Participants With All-cause Mortality Through Day 28 in the Modified Intent to Treat (MITT) Population

For each participant, survival status was assessed at Day 28 post-randomization and recorded on the electronic Case Report Form. The percentage of participants with all-cause mortality through Day 28 in the MITT population is presented.

Time frame: Up to approximately 28 days

Secondary Outcomes

Percentage of Participants Achieving a Favorable Clinical Response at Early Follow-up (EFU) Visit in the MITT Population

Clinical response was defined as "Sustained cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status with no evidence of resurgence AND no additional antibiotic therapy was required for the index infection) or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status AND no additional antibiotic therapy was required for the index infection). The percentage of participants achieving a favorable clinical response at EFU visit in the MITT population is presented.

Time frame: Up to approximately 27 days

Percentage of Participants Achieving a Favorable Clinical Response at EFU Visit in the Clinically Evaluable (CE) Population

Clinical response was defined as "Sustained cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status with no evidence of resurgence) AND no additional antibiotic therapy was required for the index infection or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status) AND no additional antibiotic therapy was required for the index infection. The percentage of participants achieving a favorable clinical response at EFU visit in the CE population is presented.

Time frame: Up to approximately 27 days

Percentage of Participants Achieving a Favorable Clinical Response at End of Therapy (EOT) Visit in the MITT Population

Clinical response was defined as "Improved" (The majority of pre-therapy signs and symptoms of the index infection have improved or resolved or returned to "pre-infection status" AND no additional antibiotic therapy was required) or "Cure" (All pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status AND no additional antibiotic therapy was required for the index infection). The percentage of participants achieving a favorable clinical response at EOT visit in the MITT population is presented.