Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Study Overview
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Brief Summary
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Inclusion of patients undergoing mechanical ventilation and presenting a pneumonia in order to determine serum pharmacokinetics of nebulized amikacin. The primary aim is to determine the dose of amikacin to be nebulized in order to observe amikacin serum concentrations close to but inferior to those observed after standart intravenous amikacin infusion.

Detailed Description
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After inclusion, patients undergo intravenous infusion of 20 mg/Kg of amikacin with amikacin serum concentrations being monitored over the following 24 hours. Randomization occures after this first amikacin infusion. Patients are randomized to group nebulized amikacin or intravenous amikacin. The three next days of the study patients recieve nebulized amikacin (or nebulized placebo) during mechanical ventilation and a placebo infusion (amikacin infusion in case of placebo nebulization) using a air driven jet nebulizer. Amikacin serum concentrations are monitored over 24 hours after each nebulization. Patients are followed up during 10 days for safety and efficacy. The dose of amikacin to be nebulized is 60 mg/Kg for the first 6 patients (phase A), 80 mg/Kg for the next 6 patients (phase B) and 100 mg/Kg for the last 6 patients (phase C). Each phase is started after review of the results of the preceeding phase by an idependent safety and monitoring board.

Official Title
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Phase II Study of High Dose Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Conditions
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Ventilator Associated Pneumonia

Intervention / Treatment
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* Drug: Nebulized amikacin
* Drug: Intravenous amikacin
* Drug: Placebo nebulization
* Drug: Placebo infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to intensive care unit. Patients undergoing mechanical ventilation for more than 48H. Suspicion of ventilator associated pneumonia. Exclusion Criteria: Allergy to amikacin or any compound of the medication. Body mass index > 30 kg/m2. Myasthenia gravis. Acute or chronic renal failure. Vestibulo-cochlear disease. Pregnancy. Brain death.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nebulized amikacin<br>Patients receive nebulized amikacin once a day during three days. Placebo is administered intravenousely | Drug: Nebulized amikacin<br>* Amikacin is nebulized at a dose of 60 mg/Kg (6 first patients of the arm), 80 mg/Kg (6 subsequent patients) or 100 mg/Kg (last 6 patients of the arm)<br>Drug: Placebo infusion<br>* 0.9% saline is administered intravenousely once a day during three days<br>|
| Active Comparator: Intravenous amikacin<br> | Drug: Intravenous amikacin<br>* 20 mg/Kg amikacin are administred intravenousely once a day during three days.<br>Drug: Placebo nebulization<br>* 0.9% saline solution is nebulized once a day during three days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determintion of nebulized amikacin dose (60 mg/Kg, 80 mg/Kg or 100 mg/Kg) which results in serum amikacin concentrations equal or below the serum amikacin concentrations measured after 20 mg/Kg intravenous amikacin infusion |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of clinical pulmonary infection score evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin |  | 10 days | 
| Comparison of serum procalcitonin concentration evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin |  | 10 days | 
| Comparison of c reactive protein evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin |  | 10 days | 
| Comparison duration of mechanical ventilation between patients treated with nebulized amikacin and patients treated with intravenous amikacin |  | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, Nebulization, Amikacin