A Safety and Tolerability Study of Doripenem Compared With Cefepime in Hospitalized Children With Bacterial Pneumonia
Condition: Pneumonia, Bacterial; Community-Acquired Infections; Nosocomial Infection; Pneumonia, Ventilator-Associated
MeSH terms: Infections; Communicable Diseases; Pneumonia; Pneumonia, Bacterial; Cross Infection; Pneumonia, Ventilator-Associated; Community-Acquired Infections
Intervention: Cefepime placebo; Cefepime; Doripenem; Doripenem placebo; Amoxicillin/clavulanate potassium
Intervention description: 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, Unit=mg, Number=50 mg/kg up to 2g/dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days; 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 each iv infusion of cefepime placebo for up to 14 days; Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately following each iv infusion of cefepime 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 cefepime.
Intervention MeSH terms: Amoxicillin; Clavulanic Acid; Clavulanic Acids; Cefepime; 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: 7.0
Sex: All
Minimum age: 3 Months
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Doripenem; Child, Hospitalized; Cefepime; Infusions, Intravenous; Severe community acquired pneumonia; Nosocomial pneumonia; Ventilator associated pneumonia

Summary:

      The purpose of this study is to evaluate the safety and tolerability of doripenem compared to
      cefepime in children hospitalized with pneumonia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Require parenteral antibacterial therapy for the treatment of pneumonia

          -  Have new or progressive radiographic infiltrate(s) (alveolar, lobar, or consolidation)
             consistent with a bacterial pneumonia that is not related to cardiac or other disease
             processes

          -  Must, based on the judgment of the investigator, require hospitalization initially and
             antibacterial therapy for 10 to 14 days for the treatment of the current pneumonia.
             (Note that the patient must require at least 3 days of IV antibiotic therapy
             initially)

          -  Have a diagnosis of nosocomial pneumonia , severe community-acquired pneumonia, or
             ventilator-associated pneumonia, defined by the disease-specific criteria as stated in
             the study protocol

          -  Have a clinical presentation compatible with bacterial pneumonia( with fever or
             hypothermia AND leukocytosis OR leucopenia AND at least 2 of the following clinical
             signs or symptoms in non-intubated patients: cough, new onset of lower respiratory
             tract secretions (including change in character of secretions or increase in the
             quantity of secretions or suctioning requirements), auscultatory findings of pneumonia
             or consolidation (rales, rhonchi bronchial breath sounds, decreased breath sounds,
             wheezing, and egophony), dyspnea, increased work of breathing expressed as
             retractions, nasal flaring, or grunting, hypoxemia or oxygen saturation less than 90%
             on room air, and tachypnea

        Exclusion Criteria:

          -  Received more than 24 hours of systemic antibacterial therapy in the 48 hours before
             the start of the infusion of the first dose of study drug for the current episode of
             pneumonia

          -  Known presence at randomization of pulmonary infection caused only by bacteria that is
             resistant to cefepime or doripenem (including methicillin resistant Staphylococcus
             aureus) or presence at baseline of pulmonary infection with Stenotrophomonas species,
             or Burkholderia cepacia

          -  Has any of the following conditions at baseline that may interfere with the diagnosis
             or response to therapy: chest trauma with severe lung contusion, acute respiratory
             distress syndrome, empyema, flail chest (severe injury to the chest), history of
             active lung cancer, chronic bronchitis with an exacerbation within the last 30 days,
             bronchiectasis (an obstructive lung disease), lung abscess(s), anatomical bronchial
             obstruction, active pulmonary tuberculosis with treatment, suspected pulmonary
             tuberculosis, suspected or documented atypical viral pneumonia without bacterial
             superinfection, suspected or documented pertussis, chemical pneumonitis (eg,
             aspiration of gastric contents, inhalation injury), or cystic fibrosis

          -  The patient has any of the following clinically significant laboratory abnormalities:
             hematocrit of less than 20%

          -  absolute neutrophil count (ANC) <500 cells/microL, platelet count <40,000
             cells/microL, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST),
             or total bilirubin >5x the age specific upper limit of normal, acute or chronic renal
             insufficiency with a baseline creatinine clearance of <60 mL/minute or requires
             dialysis therapy for any reason, or are profoundly immunodeficient and require
             prophylactic antimicrobial therapy for Pneumocystis jirovicei, Toxoplasma gondii, or
             herpes viruses, and/or chronic or intermittent immunoglobin replacement therapy.