A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections
Condition: Abscess, Intra-Abdominal; Abdominal Abscess; Abdomen, Acute; Abdominal Pain; Appendicitis; Rupture; Infection; Intestinal Perforation; Peritonitis; Ileus
MeSH terms: Infections; Communicable Diseases; Appendicitis; Abscess; Peritonitis; Intraabdominal Infections; Abdominal Abscess; Intestinal Perforation; Abdominal Pain; Abdomen, Acute; Rupture
Intervention: Doripenem; Meropenem placebo; Meropenem; Doripenem placebo; Amoxicillin/clavulanate potassium
Intervention description: Type=once every 8 hours infused over 60 minutes, Unit=mg, Number=20mg/kg up to 500mg/dose, Form=solution for infusion, Route-intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after meropenem placebo for up to 14 days; Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days.; Type=once every 8 hours infused over 30 minutes, Unit=mg, Number=20 mg/kg to 1 gram per dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv meropenem administered every 8 hours immediately before doripenem placebo for up to 14 days; Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately after each iv infusion of meropenem for up to 14 days; Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or meropenem.
Intervention MeSH terms: Amoxicillin; Meropenem; Clavulanic Acid; Clavulanic Acids; Doripenem; Amoxicillin-Potassium Clavulanate Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 3 Months
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Anti-Infective Agents; Doripenem; Meropenem; Child, Hospitalized; Complicated Intra-Abdominal Infections

Summary:

      The purpose of the study is to evaluate the safety and tolerability of doripenem compared
      with meropenem in children hospitalized with complicated intra-abdominal infections.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients who are eligible for the study must have clinical evidence of cIAI

          -  Require surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous
             drainage) to manage the cIAI

          -  Require antibacterial therapy for 5 to 14 days in addition to the surgical
             intervention

          -  Must, based on the judgment of the investigator, require hospitalization initially and
             antibacterial therapy for 5 to 14 days in addition to surgical intervention for the
             treatment of the current cIAI. (Note that the patient must require at least 3 days of
             IV antibiotic therapy initially)

          -  Have a signed informed consent form completed by the patient's parent or legal
             representative (and a signed assent form obtained from patients who are capable of
             providing assent, typically, children 7 years of age and older)

        Exclusion Criteria:

          -  Have a history of hypersensitivity reactions to carbapenems, cephalosporins,
             penicillins, or other beta-lactam antibiotics

          -  concomitant infection including but not limited to suspected or confirmed meningitis
             or central nervous system infection requiring systemic antibiotic or antifungal
             therapy in addition to the iv study drug therapy at the time of randomization

          -  Receipt of nonstudy systemic antibiotic therapy for cIAI for more than 24 hours
             immediately preceding the start of the infusion of the first dose of iv study drug
             therapy

          -  Have a diagnosis of abdominal wall abscess confined to musculature of the abdominal
             wall, small bowel obstruction or ischemic bowel disease without perforation, traumatic
             bowel perforation requiring surgery within 12 hours of perforation, or perforation of
             gastroduodenal ulcers requiring surgery within 24 hours of perforation (these are
             considered situations of peritoneal soiling before the infection has become
             established)

          -  Have simple (noncomplicated), nonperforated appendicitis or gangrenous appendicitis
             without rupture into the peritoneal cavity identified during a surgical procedure OR
             presence of spontaneous bacterial peritonitis or peritonitis associated with cirrhosis
             or chronic ascites

          -  Known at the time of randomization to have a cIAI caused by at least one pathogen that
             is nonsusceptible to doripenem or meropenem

          -  Presence of any of the following clinically significant laboratory abnormalities:
             Hematocrit of less than 20%, absolute neutrophil count (ANC) <500 cells/µL, platelet
             count <40,000 cells/µL, serum alanine aminotransferase or aspartate aminotransferase
             (AST) or total bilirubin 5 times or greater the age-specific upper limit of normal
             (ULN) or acute/chronic renal insufficiency with a baseline creatinine clearance <50 mL
             per minute or requires dialysis therapy for any reason

          -  Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6
             months before randomization