Safety, Tolerability, and Efficacy of MK-7655 (Relebactam) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone for Treating Complicated Urinary Tract Infection (cUTI) (MK-7655-003)
Condition: Urinary Tract Infections; Pyelonephritis
MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis
Intervention: Relebactam 250 mg; Relebactam 125 mg; imipenem/cilastatin 500 mg; Placebo to relebactam; Ciprofloxacin
Intervention description: Participants randomized to receive relebactam 250 mg will be administered a 250 mg dose of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval.; Participants randomized to receive relebactam 125 mg will be administered a 125 mg dose of relebactam IV in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval.; A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.; Participants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.; After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily
Intervention MeSH terms: Ciprofloxacin; Imipenem; Relebactam; Cilastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relebactam; MK-7655; Imipenem; Urinary Tract Infections; Pyelonephritis; Urologic Diseases; beta-Lactamase Inhibitors; Anti-Bacterial and Anti-Infective Agent

Summary:

      The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125
      mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older
      with complicated urinary tract infection (cUTI). The primary hypothesis is that the
      relebactam + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin
      with respect to the proportion of participants with a favorable microbiological response at
      completion of intravenous (IV) study therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        - Clinically suspected and/or bacteriologically documented cUTI or acute

        pyelonephritis judged by the investigator to be serious (requiring hospitalization and
        treatment with IV antibiotic therapy)

        - Pyuria, determined by a midstream clean-catch (MSCC) or catheterized

        (indwelling or straight catheter) urine specimen with greater than or equal to 10 white
        blood cells (WBCs) per high-power field (hpf) on standard examination of urine sediment or
        greater than or equal to 10 WBCs/mm3 in unspun urine

        - One positive urine culture within 48 hours of enrollment

        Exclusion Criteria:

        - Complete obstruction of any portion of the urinary tract (requiring a

        permanent indwelling urinary catheter or instrumentation), a known ileal loop, or
        intractable vesico-ureteral reflux

          -  A temporary indwelling urinary catheter is in place and cannot be removed at study
             entry.

          -  Perinephric or intrarenal abscess or known or suspected prostatitis

          -  Uncomplicated UTI

          -  Any history of recent accidental trauma to the pelvis or urinary tract

          -  Any amount of effective antibiotic therapy after obtaining the urine culture for
             admission to this study and prior to the administration of the first dose of IV study
             therapy

          -  An infection which has been treated with greater than 24 hours of systemic antibiotic
             therapy known to be effective against the presumed or documented etiologic pathogen(s)
             within the 72-hour period immediately prior to consideration for entry into the study

          -  History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any

        serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other beta
        (β)-lactam agents

          -  History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious
             reaction to other beta-lactam inhibitors (e.g., tazobactam, sulbactam, clavulanic
             acid)

          -  History of a seizure disorder

          -  Currently being treated with valproic acid or has received treatment with

        valproic acid in the 2 weeks prior to screening.

          -  Rapidly progressive or terminal illness unlikely to survive the approximately 6 to 8
             week study period

          -  Pregnant or expecting to conceive, breast feeding, or plans to breast feed

        during the study

        - A response to all study therapy (IV study therapy or subsequent oral

        ciprofloxacin) within the timeframe of treatment specified in this protocol is

        considered unlikely.

        - Concurrent infection that would interfere with evaluation of response to

        the study antibiotics

        - Need for concomitant systemic antimicrobial agents in addition to those

        designated in the various study treatment groups (use of vancomycin, daptomycin, or
        linezolid is allowed for certain infections)

          -  cUTI due to a confirmed fungal pathogen

          -  Currently receiving immunosuppressive therapy, including use of high-dose

        corticosteroids

          -  Prior recipient of a renal transplantation

          -  Laboratory abnormalities as specified in protocol

          -  History of any other illness that, in the opinion of the investigator, might

        confound the results of the study or pose additional risk in administering the study drug

        - 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 presentation or during the previous 30 days
        prior to screening or is anticipated to participate in such a clinical study during the
        course of this trial

        - Estimated or actual creatinine clearance of <5 mL/minute, or is currently undergoing
        hemodialysis