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

This study is currently recruiting participants.
Verified October 2017 by Merck Sharp & Dohme Corp.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02493764
First Posted: July 9, 2015
Last Update Posted: November 2, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
This study aims to compare treatment with imipenem/relebactam/cilastatin (IMI/REL) as a fixed-dose combination (FDC) with piperacillin/tazobactam (PIP/TAZ) FDC in participants with hospital-acquired and ventilator-associated bacterial pneumonia. The primary hypothesis is that IMI/REL is non-inferior to PIP/TAZ in the incidence rate of all-cause mortality.

Condition Intervention Phase
Bacterial Pneumonia Drug: Imipenem Drug: Relebactam Drug: Cilastatin Drug: Piperacillin Drug: Tazobactam Drug: Linezolid Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Official Title: A Phase III, 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of participants surviving at Day 28 [ Time Frame: Day 28 ]

Secondary Outcome Measures:
  • Percentage of participants with a favorable clinical response at early follow up visit [ Time Frame: Up to 16 days after end of therapy (up to Day 30) ]

Estimated Enrollment: 536
Actual Study Start Date: November 24, 2015
Estimated Study Completion Date: May 31, 2019
Estimated Primary Completion Date: May 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMI/REL
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.
Drug: Imipenem
Imipenem 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days
Drug: Relebactam
Relebactam 250 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days
Drug: Cilastatin
Cilastatin 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days
Drug: Linezolid
Linezolid 600 mg administered open-label by IV every 12 hours for up to 14 days
Active Comparator: PIP/TAZ
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.
Drug: Piperacillin
Piperacillin 4000 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days
Drug: Tazobactam
Tazobactam 500 mg as part of a FDC administered by IV every 6 hours for a minimum of 7 days, up to 14 days
Drug: Linezolid
Linezolid 600 mg administered open-label by IV every 12 hours for up to 14 days

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 hour 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
  Contacts and Locations
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): NCT02493764


Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 33 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02493764     History of Changes
Other Study ID Numbers: 7655A-014
2015-000246-34 ( EudraCT Number )
163240 ( Registry Identifier: JAPIC-CTI )
First Submitted: July 7, 2015
First Posted: July 9, 2015
Last Update Posted: November 2, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Bacterial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Bacterial Infections
Linezolid
Tazobactam
Penicillanic Acid
Piperacillin
Imipenem
Piperacillin, tazobactam drug combination
MK-7655
Cilastatin
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors
Protease Inhibitors