MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Complicated Intra-Abdominal Infection

Treatments: Drug: Placebo for Metronidazole; Drug: Meropenem; Drug: Ceftolozane/Tazobactam; Drug: Metronidazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT03217136

2016-004820-41 (EudraCT Number)

7625A-035

MK-7625A-035 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 94 patients

Sex: All

Ages: 7 days to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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94 participants in 2 patient groups

Ceftolozane/Tazobactam + Metronidazole

Experimental group

Description:

Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.

Treatment:

Drug: Metronidazole

Drug: Ceftolozane/Tazobactam

Meropenem + Placebo for Metronidazole

Active Comparator group

Description:

Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for Metronidazole administered IV every 8 hours for 5 to 14 days.

Treatment:

Drug: Placebo for Metronidazole

Drug: Meropenem