MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)
Condition: Complicated Intra-Abdominal Infection
MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections
Intervention: Ceftolozane/Tazobactam; Metronidazole; Meropenem; Placebo for Metronidazole
Intervention description: Ceftolozane 20 mg/kg (maximum 1 g) and tazobactam 10 mg/kg (maximum 0.5 g/dose) administered IV every 8 hours for between 5 to 14 days.; Metronidazole 10 mg/kg (maximum 1.5 g/day) administered IV every 8 hours for between 5 to 14 days. Participants ≤ 28 days old, start with a loading dose of 15 mg/kg; then if ≤ 2 kg are dosed 7.5 mg/kg/ every 12 hours; or if > 2 kg are dosed 10 mg/kg every 8 hours.; Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 5 to 14 days.; Placebo for metronidazole administered IV every 8 hours for between 5 to 14 days.
Intervention MeSH terms: Metronidazole; Meropenem; Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 94.0
Sex: All
Minimum age: 7 Days
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      This study aims to evaluate the safety and tolerability of MK-7625A (ceftolozane/tazobactam)
      plus metronidazole, compared with that of meropenem in pediatric participants with cIAI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a legally acceptable representative who provides documented informed
             consent/assent for the trial.

          -  Aged from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18
             years of age.

          -  Require IV antibacterial therapy for the treatment of presumed or documented cIAI.

          -  Has an operative procedure for the current diagnosis and management of cIAI planned or
             completed within 24 hours of the first dose of an antibacterial drug. Note:
             Participants with a diagnosis of necrotizing enterocolitis are exempt and not required
             to have surgery planned or completed in order to be eligible.

          -  Has in compliance baseline intra-abdominal specimen collection.

          -  Is not of reproductive potential; but if of reproductive potential agrees to avoid
             becoming pregnant or impregnating a partner during screening, while receiving study
             treatment and for at least 30 days after the last dose of study treatment.

          -  Female of reproductive potential is not pregnant, and not planning to become pregnant
             within 30 days of the last day of treatment administration; and is nonlactating.

        Exclusion Criteria:

          -  Is currently participating in or has participated in an interventional clinical trial
             with an investigational compound or device within 30 days prior to the first dose of
             study treatment in this current trial.

          -  Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or
             has enrolled previously in the current trial and been discontinued.

          -  Has a history of any moderate or severe hypersensitivity (e.g, anaphylaxis), allergic
             reaction, or other contraindication to any of the following: β-lactam antibiotics
             (e.g, penicillins, cephalosporins, and carbapenems), β-lactamase inhibitors (e.g,
             tazobactam, sulbactam, clavulanic acid, avibactam), or metronidazole.

          -  Has an IAI within the past 1 year prior to randomization known to be caused by a
             pathogen resistant to either IV study treatment.

          -  Has a concomitant infection at the time of randomization that requires non-study
             systemic antibacterial therapy in addition to IV study treatment or oral step-down
             therapy.

          -  Has received potentially therapeutic antibacterial therapy for a duration more than 24
             hours during the 48 hours preceding the first dose of study treatment, unless is
             considered to be failing antibiotic therapy for cIAI.

          -  Has any of the following: a) intractable cIAI that the investigator anticipates would
             require more than 14 days of study treatment; b) abdominal wall abscess; c) small
             bowel obstruction; d) ischemic bowel disease without perforation; e) traumatic bowel
             perforation with surgery within 12 hours of perforation; f) perforation of
             gastroduodenal ulcers requiring surgery within 24 hours of perforation; g) suspected
             uncomplicated intra-abdominal infection (e.g, cholecystitis without rupture or
             extension beyond the gallbladder wall); h) acute suppurative cholangitis; i) infected
             necrotizing pancreatitis; j) pancreatic abscess.

          -  Has moderate or severe impairment of renal function.

          -  Has a seizure disorder or is anticipated to be treated with divalproex sodium or
             valproic acid during the course of study treatment.

          -  Is receiving, or is expected to receive, any prohibited medications.

          -  Has any rapidly progressing disease or immediately life-threatening illness, including
             acute hepatic failure, respiratory failure, or septic shock.

          -  Has an immunocompromising condition.

          -  Has a history of malignancy ≤5 years prior to signing informed consent.

          -  Is planning to receive suppressive/prophylactic antibiotics with gram-negative
             activity after completion of study treatment.