Study of the Safety, Tolerability, and Efficacy of Relebactam (MK-7655) + Imipenem/Cilastatin Versus Imipenem/Cilastatin Alone to Treat Complicated Intra-Abdominal Infection [cIAI] (MK-7655-004)
Condition: Intra-abdominal Infections
MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections
Intervention: Relebactam 250 mg; Relebactam 125 mg; Imipenem/cilastatin; Matching placebo to relebactam
Intervention description: Relebactam 250 mg IV every 6 hours for a minimum of 96 hours; Relebactam 125 mg IV every 6 hours for a minimum of 96 hours; 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.; Placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.
Intervention MeSH terms: Imipenem; Relebactam; Cilastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 351.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Complicated Intra-abdominal Infections

Summary:

      The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125
      mg or 250 mg doses of relebactam (MK-7655) to imipenem/cilastatin in adults 18 years or older
      with Complicated Intra-Abdominal Infection (cIAI). The primary hypothesis is that the
      relebactam + imipenem/cilastatin treatment regimen is non-inferior to treatment with
      imipenem/cilastatin alone with respect to the percentage of participants with a favorable
      clinical response at completion of intravenous (IV) study therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinically suspected and/or bacteriologically documented cIAI requiring
             hospitalization and treatment with IV antibiotic therapy.

          -  Enrolled intraoperatively or postoperatively on the basis of operative findings OR
             enrolled preoperatively on the basis of compelling preoperative clinical findings.

        Exclusion Criteria:

          -  Infection which should be managed by Staged Abdominal Repair (STAR) or open abdomen
             technique.

          -  Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 30.

          -  Any amount of effective antibiotic therapy after obtaining the 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 >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 β-lactam
             agents.

          -  History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious
             reaction to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic
             acid).

          -  History of a seizure disorder (requiring ongoing treatment with anticonvulsive therapy
             or prior treatment with anti-convulsive therapy in the last 3 years).

          -  Currently being treated with valproic acid or has used 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, breastfeeding, or plans to breast feed within 1
             month of completion of the study.

          -  Participant in whom a response to IV study therapy 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.

          -  cIAI due to a confirmed fungal pathogen.

          -  Currently receiving immunosuppressive therapy, including use of high-dose
             corticosteroids.

          -  Prior recipient of a renal transplantation.

          -  Estimated or actual creatinine clearance of <50 mL/minute.

          -  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 to
             the patient.

          -  Laboratory abnormalities as specified in protocol.

          -  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 the trial.