Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013)
Condition: Bacterial Infections
MeSH terms: Infections; Communicable Diseases; Bacterial Infections
Intervention: Imipenem+Cilastatin/Relebactam; Colistimethate sodium (CMS); Imipenem+Cilastatin; Placebo to CMS
Intervention description: Imipenem+Cilastatin/Relebactam 200/100 mg to 500/250 mg, depending on renal function, IV infusion once every 6 hours; Colistimethate base activity 300 mg (~720 mg CMS) IV infusion loading dose, followed by colistimethate base activity 75 mg to 150 mg (~180 to 360 mg CMS), depending on renal function, once every 12 hours; Imipenem+cilastatin 200 mg to 500 mg, depending on renal function, IV infusion once every 6 hours; Placebo to CMS IV infusion once every 12 hours
Intervention MeSH terms: Imipenem; Relebactam; Cilastatin, Imipenem Drug Combination; Cilastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study will evaluate the efficacy and safety of imipenem+cilastatin/relebactam (MK-7655A)
      versus colistimethate sodium+imipenem+cilastatin in the treatment of imipenem-resistant
      bacterial infections. Infections evaluated in the study will be hospital-acquired bacterial
      pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), complicated
      intra-abdominal infection (cIAI), and complicated urinary tract infection (cUTI).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Hospitalization that requires treatment with IV antibiotic therapy for a new,
             persistent or progressing bacterial infection involving at least 1 of 3 primary
             infection types (HABP, VABP, cIAI, or cUTI)

          -  Positive culture data from the primary infection-site specimen collected within 1 week
             of study entry. At least one of the suspected causative pathogens from the specimen
             meets all of the following: 1) identified as a Gram-negative bacterium, 2)
             culture-confirmed imipenem resistance (and colistin resistance for Group 3 only), 3)
             culture-confirmed susceptibility to imipenem/relebactam and to colistin (for Groups 1
             and 2 only)

          -  Not of reproductive potential, or of reproductive potential and agrees to avoid
             becoming pregnant or impregnating a partner by complying with one of the following: 1)
             practice abstinence, or 2) use of acceptable contraception during heterosexual
             activity

        Exclusion Criteria:

          -  Concurrent infection (endocarditis, osteomyelitis, meningitis, prosthetic joint
             infection, disseminated fungal infection, or active pulmonary tuberculosis) that would
             interfere with evaluation of the response to the study antibiotics

          -  Received treatment with any form of systemic colistin for >24 hours within 72 hours
             before initiation of study drug (for Groups 1 and 2 only)

          -  HABP or VABP caused by an obstructive process

          -  cUTI which meets any of the following: 1) complete obstruction of any portion of the
             urinary tract, 2) known ileal loop, 3) intractable vesico-ureteral reflux, 4) presence
             of an indwelling urinary catheter which cannot be removed at study entry

          -  History of serious allergy, hypersensitivity, or any serious reaction to listed
             antibiotics (per-protocol)

          -  Female who is pregnant or is expecting to conceive (or a male partner of a female who
             is expecting to conceive), is breastfeeding, or plans to breastfeed before completion
             of the study

          -  Anticipated treatment with any of the following during the study: valproic acid or
             divalproex sodium, or concomitant systemic (e.g. IV, oral or inhaled) antimicrobial
             agents with known Gram-negative bacterial coverage

          -  Currently undergoing hemodialysis or peritoneal dialysis

          -  Participated or anticipates participating in any other clinical study involving
             administration of investigational medication up to 30 days before screening or during
             the course of the trial