A Safety and Tolerability Study of Doripenem in Patients With Abdominal Infections or Pneumonia
Condition: Pneumonia, Ventilator-Associated; Pneumonia, Bacterial; Pneumonia; Abdominal Abscess; Bacterial Infections
MeSH terms: Infections; Communicable Diseases; Pneumonia; Bacterial Infections; Intraabdominal Infections; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Abdominal Abscess
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to assess the safety and tolerability of doripenem compared to
      imipenem in Ventilator-assisted pneumonia and complicated Intra-abdominal Infection. The
      study population will include hospitalized patients (or patients resident in a chronic health
      care facility) who have a diagnosis of either Ventilator associated pneumonia or complicated
      Intra-abdominal Infection.
    

Detailed description: 
      This is a randomized (study drug assigned by chance), open-label (all people involved know
      the identity of the intervention), multicenter study that will evaluate the safety and
      tolerability of doripenem (an antibiotic used to treat infections) in patients with
      ventilator-associated pneumonia (VAP) or complicated intra-abdominal infection (cIAI).
      Approximately 250 patients will be assigned in a 3:1 ratio to receive doripenem or
      imipenem/cilastatin (188 patients randomized to receive doripenem and 62 patients randomized
      to receive imipenem/cilastatin). Furthermore, patients who receive doripenem or
      imipenem/cilastatin will be stratified by disease (VAP or cIAI). Therefore, for reporting
      purposes, there will be 4 groups: Patients with VAP treated with doripenem, patients with VAP
      treated with imipenem/cilastatin, patients with cIAI treated with doripenem, and patients
      with cIAI treated with imipenem/cilastatin. Study drug will be administered intravenously
      (iv) (through a vein) for 7 to 14 days for patients with VAP and for 5 to 14 days for
      patients with cIAI. The maximum duration of study drug is 14 days. Vancomycin and/or amikacin
      may be added to the study drug regimen as adjunctive therapy for those patients who meet
      study specified criteria. The recommended dosage of vancomycin is 1 g every 12 hours
      administered by iv infusion. The addition of amikacin is at the discretion of the
      investigator for patients with VAP (not cIAI) and the recommended dosing regimen for amikacin
      is 15 mg/kg given iv once a day. Alternative amikacin regimens or other aminoglycoside
      regimens may be permitted. Safety will be assessed during the study by the monitoring of
      adverse events, evaluation of laboratory test results, and changes in vital signs. The
      primary endpoint of this study is to assess the overall incidence of treatment-emergent
      adverse events (TEAEs) from the initiation of the first infusion of study drug and up to 30
      days after the completion of study drug therapy. Treatment-emergent adverse events are
      defined as adverse events that occur or worsen between the initial infusion of study drug up
      to 30 days after the last dose of study drug. The hypothesis for this study is that doripenem
      has a similar safety profile to imipenem. Doripenem (1g at 8-hour intervals over a period of
      4 hours) or imipenem/cilastatin (1g at 8-hours over a period of 1 hour) will be administered
      by intravenous (iv) infusion (delivery of drug slowly into the vein over a period of time).
      Patients diagnosed with ventilator associated pneumonia (VAP) will be treated for 7 to 14
      days and patients with complicated intra-abdominal infections (cIAI) will be treated for 5 to
      14 days.
    

Intervention name(s): Imipenem/cilastatin; Imipenem/cilastatin; Doripenem; Doripenem
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion; Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion; 1 gram infused over 4 hours at 8-hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days; 1 gram infused over 1 hour at 8 hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days
Intervention MeSH terms: Imipenem; Doripenem; Cilastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Doripenem; Imipenem; Cilastatin; Vancomycin; DORIBAX, DORIPREX, FINIBAX, DURAPTA, PRIMAXIN, Anti Bacterial Agents; Ileus; Hospitalized; Fever