Imipenem/Relebactam/Cilastatin Versus Piperacillin/Tazobactam for Treatment of Participants With Bacterial Pneumonia (MK-7655A-014) (RESTORE-IMI 2)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Bacterial Pneumonia

Treatments: Drug: Imipenem; Drug: Linezolid; Drug: Relebactam; Drug: Piperacillin; Drug: Cilastatin; Drug: Tazobactam

Study type: Interventional

Funder types: Industry

Identifiers

NCT02493764

7655A-014

163240 (Registry Identifier)

2015-000246-34 (EudraCT Number)

MK-7655A-014 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 537 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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537 participants in 2 patient groups

IMI/REL

Experimental group

Description:

Imipenem 500 mg + relebactam 250 mg + cilastatin 500 mg as a FDC administered intravenously (IV) every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.

Treatment:

Drug: Cilastatin

Drug: Relebactam

Drug: Linezolid

Drug: Imipenem

PIP/TAZ

Active Comparator group

Description:

Piperacillin 4000 mg + tazobactam 500 mg as a FDC administered IV every 6 hours for a minimum of 7 days, up to 14 days. At study entry open label linezolid 600 mg will also be administered by IV every 12 hours for up to 14 days.

Treatment:

Drug: Tazobactam

Drug: Linezolid

Drug: Piperacillin