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)

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

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).

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Amikacin (BAY41-6551); Drug: Amikacin (BAY41-6551); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers Cedex 9, France, 49933
  • Limoges Cedex, France, 87046
  • Paris, France, 75018
  • Paris Cedex 13, France, 75651
  • Paris Cedex 14, France, 75674
  • Paris Cedex 15, France, 75908
  • Rouen cedex, France, 76031
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28040
  • Madrid, Spain, 28034
  • Madrid, Spain, 28805
  • Murcia, Spain, 30120
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
  • Florida
    • Melbourne, Florida, United States, 32901
  • New York
    • Albany, New York, United States, 12208
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
  • Ohio
    • Columbus, Ohio, United States, 43210
  • Texas
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Nektar Therapeutics

Publications and helpful links

General Publications

• Niederman MS, Chastre J, Corkery K, Fink JB, Luyt CE, Garcia MS. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med. 2012 Feb;38(2):263-71. doi: 10.1007/s00134-011-2420-0. Epub 2011 Dec 7.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: October 29, 2009
• First Submitted That Met QC Criteria: October 29, 2009
• First Posted (Estimate): October 30, 2009

Study Record Updates

• Last Update Posted (Estimate): April 8, 2011
• Last Update Submitted That Met QC Criteria: April 7, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Pneumonia; Gram-negative bacteria; Adjunctive treatment
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents; Amikacin
• Other Study ID Numbers: AMIK-04-02