Clinical Trial: Inhaled Amikacin Solution (BAY 41-6551) as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia

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

Official Title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patient

Brief 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).

Detailed Summary:
Sponsor: Bayer

Current Primary Outcome: Proportion of patients deemed to be clinical successes in the BAY41-6551 treatment group divided by the proportion of cured patients in the placebo treatment group [ Time Frame: Late follow-up (LFU) visit (day 28-32) ]

Original Primary Outcome: The Primary efficacy variable will be the clinical response at the test -of-Cure (TOC) visit in the modified Intent -to-Treat (ie, ITT population plus a pre-therapy culture positive for a respiratory tract pathogen) population [ Time Frame: 17-19 days after start of treatment with study medication ]

Current Secondary Outcome:

  • Pneumonia-related mortality through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Early Clinical Response which is based on CPIS scores, the presence of empyema or lung abscess, and all-cause mortality [ Time Frame: Assessed through day 10 ]
    Early Clinical Response success occurs if there is no rise of 2 points or more on Day 3, and a drop of 1 or more points on Day 5 and a drop 2 or more points on Day 10, and the absence of lung abscess or empyema by Day 10, and alive on Day 10.
  • Number of days on mechanical ventilation through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Number of days in the ICU through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Number of patients who received at least one dose of study drug and reported an adverse event [ Time Frame: 35-39 days after start of treatment with study medication ]
  • Number of patients who received at least one dose of study drug and reported a serious adverse event [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Progression and incidence rates of organ failure [ Time Frame: 28-32 days after start of treatment with study medication ]
  • All-cause mortality rate [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Identification of laboratory data outside normal ranges [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Per pathogen microbiological response rates at the Test-of-Cure (TOC) visit [ Time Frame: 17-19 days after start of treatment with study medication ]
  • Per patient microbiological response rates at the TOC visit [ Time Frame: 17-19 days after start of treatment with study medication ]
  • Microbiological recurrence rates at the TOC and LFU visits [ Time Frame: 17-19 days and 28-32 days respectively after start of treatment with study medication ]
  • Emergence of new respiratory pathogens during the aerosol treatment period [ Time Frame: Days 1-10 ]
  • Emergence of resistance among baseline pathogens in those patients with persistent infection or colonization [ Time Frame: 28-32 days after start of treatment with study medication ]


Original Secondary Outcome:

  • Number of days on mechanical ventilation through the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Number of IV antibiotics per patient per day used at the TOC and Day 28 visits [ Time Frame: 17-19 days and then 28-32 days after start of treatment with study medication ]
  • Number of intensive care unit (ICU) days at the Day 28 visit, number of hospital days at the Day 28 visit, clinical relapse rates at the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ]
  • Mortality during the treatment period, Day 15, and Day 28 visit [ Time Frame: Days 1-10 (treatment period), Day 15 and then Days 28-32 after start of treatment with study medication ]
  • Per pathogen microbiological response rates at the TOC visit per patient microbiological response rate at the TOC visit [ Time Frame: 17-19 days after start of treatment with study medication ]
  • Microbiological recurrence rates at the TOC and Day 28 visit Emergence of new potential respiratory pathogens during the treatment period, Emergence of resistance among baseline pathogens in those patients with persistent infection or colonization [ Time Frame: 17-19 days after start of treatment with study medication ]


Information By: Bayer

Dates:
Date Received: December 8, 2008
Date Started: May 28, 2013
Date Completion:
Last Updated: May 5, 2017
Last Verified: May 2017