A Study to Determine the Correct Dose of Amikacin Which is Delivered Directly to the Lungs of Ventilated Patients as an Aerosol Via an Investigational Device Called the Pulmonary Delivery Device System (PDDS)

Study Overview
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Brief Summary
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This study is part of a research program too see if amikacin delivered as an aerosol directly to the lungs in combination with IV antibiotic therapy can help intubated patients with gram-negative pneumonia get better faster than when given intravenous antibiotics alone. The primary purpose of this study is to determine the correct dose of amikacin which is delivered directly to the lungs as an aerosol via an investigational device called the Pulmonary Delivery Device System (PDDS).

Official Title
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A Double-Blind, Placebo-controlled Parallel Group, Phase II Dose-Ranging Study of Nebulized Amikacin Delivered Via the Pulmonary Drug Delivery System (PDDS) in Ventilated Patients With Nosocomial Pneumonia Due to Gram Negative Organisms

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: Amikacin (BAY41-6551)
* Drug: Amikacin (BAY41-6551)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years of age or older with a clinical diagnosis of VAP, HAP or HCAP who are expected to be on mechanical ventilation for at least 3 days Exclusion Criteria: Patients with compromised of suppressed immune systems, severe hypoxemia, PEEP>15cm H2O, creatinine>2 mg/dL, or who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Amikacin (BAY41-6551)<br>* Single daily dose of 400 mg aerosolized amikacin and a single dose of aerosolized placebo on a rotating every 12hr schedule<br>|
| Experimental: Arm 2<br> | Drug: Amikacin (BAY41-6551)<br>* Daily dose of 800 mg aerosolized amikacin delivered in two divided doses of 400 mg per aerosol treatment every 12hr<br>|
| Placebo Comparator: Arm 3<br> | Drug: Placebo<br>* Two aerosol treatments per day (one treatment every 12hr)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve a C(max) for amikacin in tracheal aspirates at least 25 times greater than the reference MIC for hospital-acquired organisms and an AUC (0-24 hr) / MIC ratio that is 100 or greater on Day 1 |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean C(max) and mean AUC of amikacin in tracheal aspirates |  | Day 1 and Day 3 of treatment period | 
| Mean ratio of C (max) / MIC and mean ratio of AUC (0-24 hr) / MIC |  | Day 1 and Day 3 of treatment period | 
| Clinical cure rate |  | Test of cure visit (7 days post last treatment dose) | 
| Microbiological eradication rate of identified pathogens |  | Test of cure visit (7 days post last treatment dose) | 
| Microbiological persistence rate |  | Test of cure visit (7 days post last treatment dose) | 
| New infection rate |  | Test of cure visit (7 days post last treatment dose) | 
| Assessment of adverse events related to drug or device |  | Treatment period, early post treatment period, test of cure visit, and late post treatment | 
| Assessment of abnormal laboratory values |  | Treatment period, early post treatment period, test of cure visit, and late post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, Adjunctive treatment, Gram-negative bacteria