Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
Condition: Pneumonia, Bacterial
MeSH terms: Pneumonia; Pneumonia, Bacterial
Intervention: Amikacin Inhalation Solution (BAY41-6551); Aerosolized Placebo
Intervention description: 400 mg of aerosolized amikacin every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical); Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)
Intervention MeSH terms: Amikacin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 725.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gram-negative pneumonia; Intubation; Mechanical ventilation; Amikacin

Summary:

      To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg
      (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System
      (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal
      saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and
      mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint
      objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized
      placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on
      ventilation, and the days in the intensive care unit (ICU).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and non-pregnant, non-lactating females, 18 years of age or older

          -  Intubated and mechanically-ventilated

          -  Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on
             chest radiograph

          -  Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory
             secretions, or suspected Gram-negative pathogen

          -  Impaired oxygenation

          -  Clinical Pulmonary Infection Score (CPIS) of at least 6

          -  Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory
             specimen OR at least two risk factors for MDR organisms

        Exclusion Criteria:

          -  History of hypersensitivity to amikacin or other aminoglycosides

          -  Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours
             at the time of randomization

          -  Known or suspected bacteremia secondary to Staphylococcus aureus

          -  A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test

          -  Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a
             serum creatinine > 2 mg/dL (177 µmol/L) and being treated with continuous renal
             replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or
             daily hemodialysis will receive the aerosol study drug treatment]

          -  Has been on mechanical ventilation for > 28 days

          -  Is participating in or has participated in other investigational interventional
             studies within the last 28 days prior to study treatment

          -  The risk of rapidly fatal illness and death within 72 hrs, or any concomitant
             condition not related to ventilator-associated pneumonia that, in the opinion of the
             investigator, precludes completion of study evaluations and the course of therapy

          -  Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10

          -  Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V
             ECMO)