Clinical Trial: Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Blinded, Placebo-Controlled, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® Inline System in Mechanically Ventilated Patients With Gram

Brief Summary: To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin fosfomycin inhalation system (AFIS) versus aerosolized placebo to treat Gram-negative pneumonia in mechanically ventilated patients receiving IV antibiotics.

Detailed Summary: The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution and fosfomycin solution, delivered by aerosol to the lungs via the PARI Investigational eFlow Inline System (eFlow Inline System). All patients will receive a standardized course of intravenous (IV) antibiotics for a minimum of 7 days. Patients will be randomized to receive 10 days of treatment with either AFIS or placebo, in addition to the IV therapy. The primary efficacy endpoint is defined as the change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of study drug.
Sponsor: Cardeas Pharma

Current Primary Outcome: Change from baseline in Clinical Pulmonary Infection Score (CPIS) during the planned 10-day treatment period. [ Time Frame: 10 day treatment period. ]

Daily CPIS will be determined by one blinded, central reviewer in order to minimize inter-observer variability.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Composite endpoint of mortality and clinical cure [ Time Frame: Day 1 - Day 28 ]
    The hierarchical composite endpoint of mortality, then clinical cure (defined as both absence of Gram-negative bacteria and CPIS at Day 14 < 6).
  • Composite endpoint of mortality and ventilator-free days [ Time Frame: Day 1- Day 28 ]
    The hierarchical composite endpoint of mortality, then ventilator-free days.
  • Number of days free of mechanical ventilation from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Number of ICU days from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Microbiological response rates in patients positive for multi-drug resistant Gram-negative bacteria [ Time Frame: Day 14 ]
    Microbiological response rates at Day 14 in patients whose pre-study treatment bronchoalveolar lavage (BAL) was positive for multi-drug resistant Gram-negative bacteria
  • Mortality from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Clinical relapse rate [ Time Frame: Day 11 - Day 28 ]
    Clinical relapse rates (defined as a new episode of pneumonia requiring reinstitution of IV antibiotics) from Day 11 through Day 28


Original Secondary Outcome:

  • Composite endpoint of mortality and ventilator-free days [ Time Frame: Day 1- Day 28 ]
    The hierarchical composite endpoint of mortality and ventilator-free days.
  • Number of days free of mechanical ventilation from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Number of ICU days from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Microbiological response rates in patients positive for multi-drug resistant Gram-negative bacteria [ Time Frame: Day 14 ]
    Microbiological response rates at Day 14 in patients whose pre-study treatment bronchoalveolar lavage (BAL) was positive for multi-drug resistant Gram-negative bacteria
  • Mortality from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ]
  • Clinical relapse rate [ Time Frame: Day 11 - Day 28 ]
    Clinical relapse rates (defined as a new episode of pneumonia requiring reinstitution of IV antibiotics) from Day 11 through Day 28


Information By: Cardeas Pharma

Dates:
Date Received: October 22, 2013
Date Started: December 2013
Date Completion:
Last Updated: May 9, 2016
Last Verified: March 2016