To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia
Condition: Ventilator-Associated Pneumonia
MeSH terms: Pneumonia; Pneumonia, Ventilator-Associated
Intervention: Doripenem; Imipenem-Cilastatin; Placebo
Intervention description: Type=exact number, number=1, unit=g, form=solution for injection, route=intravenously. 1 gram 4-hour infusion of doripenem will be administered every 8 hours for 7 days.; Type=exact number, number=1, unit=g, form=solution for injection, route=intravenously. 1 gram 1-hour infusion of imipenem-cilastatin will be administered every 8 hours for 10 days.; Form=solution, route=intravenous. Doripenem pacebo will be administered from Days 1 to 7 in imipenem-cilastatin arm and imipenem-cilastatin placebo will be administered in doripenem arm.
Intervention MeSH terms: Imipenem; Doripenem; Cilastatin, Imipenem Drug Combination; Cilastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 274.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ventilator-Associated Pneumonia; Pneumonia, hospital-acquired; Doripenem; Imipenem-cilastatin

Summary:

      The purpose of this study is to show that doripenem is as effective as imipenem-cilastatin in
      the treatment of patients with ventilator-associated pneumonia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have new or worsening radiographic infiltrates consistent with
             ventilator-associated pneumonia that was not related to cardiac or other disease
             processes

          -  Have at least 1 of the following: fever (core body temperature greater than 39.0°C);
             hypothermia (core body temperature of less than 35.0°C); leukocytosis (increased WBC
             count); and leukopenia (decreased WBC count)

          -  Have developed ventilator-associated pneumonia and have been on mechanical ventilation
             for more than or equal to 48 hours and on mechanical ventilation at the time that
             study medication is assigned

          -  Have been hospitalized or been in a chronic care facility for consecutive 5 days or
             more within the last 90 days

          -  Have a baseline Clinical Pulmonary Infection Score (CPIS) more than or equal to 6 and
             an Acute Physiology and Chronic Health Evaluation (APACHE) II score more than 8 and
             less than 35

        Exclusion Criteria:

          -  Have received antibiotics for this episode of ventilator-associated pneumonia for more
             than 24 hours before study medication administration

          -  Known presence at baseline of only methicillin-resistant Staphylococcus aureus or
             Stenotrophomonas infection

          -  Acute respiratory distress syndrome

          -  Has any of the following conditions: chest trauma with severe lung bruising or loss of
             stability of the thoracic cage following a fracture of the sternum, ribs, or both,
             increased amounts of fluid in the lung cavities requiring drainage or pus in the
             cavity

          -  Has active seizure disorder within the last 2 years or brain injury such that imipenem
             cilastatin would not be administered to the patient in usual practice

          -  Has lung cancer within the last 2 years, chronic bronchitis with an increase in
             severity within the last 30 days, chronic enlargement of the bronchi or bronchioles
             related to inflammatory disease or obstruction, lung abscess(s), anatomical bronchial
             obstruction, respiratory tuberculosis on treatment, suspected atypical pneumonia,
             chemical pneumonitis, cystic fibrosis, congestive heart failure, severe burns to
             greater than 15% of the body, evidence of severe and chronic liver disease