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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03583333
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : July 20, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This study will evaluate the efficacy and safety of imipenem/cilastatin/relebactam (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.

Condition or disease Intervention/treatment Phase
Hospital-Acquired Bacterial Pneumonia Ventilator-Associated Bacterial Pneumonia Drug: IMI/REL FDC Drug: PIP/TAZ FDC Drug: Linezolid Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 274 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-national Phase 3, 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
Actual Study Start Date : September 18, 2018
Actual Primary Completion Date : July 12, 2022
Actual Study Completion Date : July 12, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: IMI/REL 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/500 mg Cilastatin, 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.
Drug: IMI/REL FDC
500 mg Imipenem, 500 mg Cilastatin and 250 mg Relebactam powder FDC provided in a single vial
Other Name: MK-7655A

Drug: Linezolid
Open-label 600 mg Linezolid

Active Comparator: PIP/TAZ FDC
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.
Drug: PIP/TAZ FDC
4000 mg Piperacillin and 500 mg Tazobactam powder FDC provided in a single vial

Drug: Linezolid
Open-label 600 mg Linezolid




Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: Up to Day 28 ]
    Percentage of participants with all-cause mortality through Day 28


Secondary Outcome Measures :
  1. Favorable clinical response at end of treatment (EOT) visit [ Time Frame: From treatment Day 7 up to Day 15 ]
    Percentage of participants achieving a favorable clinical response at EOT visit.

  2. Favorable clinical response at early follow-up (EFU) visit [ Time Frame: 7-14 days post-EOT (up to Day 28) ]
    Percentage of participants achieving a favorable clinical response at EFU visit

  3. Favorable microbiological response at EFU visit. [ Time Frame: 7-14 days post-EOT (up to Day 28) ]
    Percentage of participants achieving a favorable microbiological response at EFU visit.

  4. Favorable microbiological response at EOT visit. [ Time Frame: From treatment Day 7 up to Day 15 ]
    Percentage of participants achieving a favorable microbiological response at EOT visit.

  5. Adverse Events [ Time Frame: Up to Day 31 ]
    Number of participants experiencing adverse events

  6. Discontinuations due to adverse events [ Time Frame: Up to Day 14 ]
    Number of participants discontinuing study drug due to adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03583333


Locations
Show Show 68 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT03583333    
Other Study ID Numbers: 7655A-016
MK-7655A-016 ( Other Identifier: Merck Protocol Number )
PHRR190814-002177 ( Registry Identifier: PHRR )
2018-003202-82 ( EudraCT Number )
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Pneumonia
Pneumonia, Bacterial
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Bacterial Infections
Bacterial Infections and Mycoses
Linezolid
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action