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

Phase 2

Completed

Conditions: Complicated Intra-Abdominal Infection

Interventions: Drug: Ceftolozane/Tazobactam
Drug: Meropenem
Drug: Placebo for Metronidazole
Drug: Metronidazole

Registration Number: NCT03217136

Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 94

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ceftolozane/Tazobactam + Metronidazole	Ceftolozane/Tazobactam	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.
Meropenem + Placebo for Metronidazole	Placebo for Metronidazole	Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for Metronidazole administered IV every 8 hours for 5 to 14 days.
Ceftolozane/Tazobactam + Metronidazole	Metronidazole	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.
Meropenem + Placebo for Metronidazole	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for Metronidazole administered IV every 8 hours for 5 to 14 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing ≥1 Adverse Events (AEs)	Up to approximately 75 days	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Number of Participants Who Discontinued Study Therapy Due to AE(s)	Up to approximately 18 days	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Clinical Response of "Cure" at the End of Treatment (EOT) Visit	Up to approximately 27 days	The percentage of participants who had a clinical outcome of "cure" at the time of the EOT visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.
Percentage of Participants With a Clinical Response of "Cure" at the Test of Cure (TOC) Visit	Up to approximately 39 days	The percentage of participants who had a clinical outcome of "cure" at the time of the TOC visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.
Percentage of Participants With Microbiological Eradication at the EOT Visit	Up to approximately 27 days	The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the EOT visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.
Percentage of Participants With Microbiological Eradication at the TOC Visit	Up to approximately 39 days	The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the TOC visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.

Trial Locations

Locations (50): Children's Hospital - Los Angeles ( Site 2508)
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Los Angeles, California, United States
Children's Hospital of Orange County ( Site 2502)
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Orange, California, United States
Rady Children's Hospital-San Diego ( Site 2505)
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San Diego, California, United States
Baptist Medical Center/Wolfson Children's Hospital ( Site 2521)
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Jacksonville, Florida, United States
Tufts Medical Center-Floating Hospital for Children ( Site 2516)
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Boston, Massachusetts, United States
St. Louis Children's Hospital ( Site 2511)
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Saint Louis, Missouri, United States
SUNY Upstate Medical University Hospital ( Site 2509)
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Syracuse, New York, United States
Primary Children's Hospital ( Site 2500)
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Salt Lake City, Utah, United States
Seattle Childrens Hospital ( Site 2510)
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Seattle, Washington, United States
Hospital Pequeno Principe ( Site 0200)
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Curitiba, Parana, Brazil
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Children's Hospital - Los Angeles ( Site 2508)
🇺🇸Los Angeles, California, United States