Effect of Additional Nebulized Amikacin in Ventilator-Associated Pneumonia Caused by Gram Negative Bacteria

Study Overview
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Brief Summary
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The purpose of this study is to determine the cure rate from ventilator-associated pneumonia (VAP) caused by Gram negative bacteria when administering add on nebulized amikacin to intravenous antibiotics compared to intravenous antibiotics alone.

Detailed Description
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After inclusion, the patients are randomized into two groups: nebulized amikacin plus intravenous antibiotic(s) or nebulized placebo plus intravenous antibiotic(s). The dose of nebulized amikacin is 400 mg every 12 hours for 10 days. The patients are followed up on day 3, 7, 10, and 28 for safety and efficacy. The estimate sample size is 84 subjects base on previous study of cure rate in VAP and the authors expected that nebulized amikacin can improve cure rate in VAP subjects for 30% when compared with intravenous antibiotic(s) alone with power of 80% at level of significance 0.05.

Official Title
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Effect of Additional Nebulized Amikacin in Ventilator-Associated Pneumonia Caused by Gram Negative Bacteria

Conditions
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Pneumonia, Ventilator-Associated

Intervention / Treatment
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* Drug: Amikacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >/= 18 years On mechanical ventilator more than 7 days VAP diagnosis inclusion criteria: new/progressive infiltration of chest radiography 2/3 of the following: 1) fever 2) purulent sputum 3) Wbc > 12,000 cell/mm3 or < 4,000 cell/mm3 Evidence of gram negative bacilli from sputum gram stain or previous sputum culture within 1 week Exclusion Criteria: History of amikacin allergy GFR < 30 mL/min except dialytic patients Immunocompromised host: HIV CD4 < 200 cells/mm3, leukemia, lymphoma, received chemotherapy within 3 weeks, Absolute neutrophil count < 500/mm3 Severe ARDS (P/F ratio < 100) Endobronchial obstruction:endobronchial mass, endobronchial stenosis Atelectasis Severe bronchospasm Lung abscess Complicated parapneumonic effusion/ Empyema Chest trauma Uncontrolled extrapulmonary infection(s) Received intravenous antibiotic(s) more than 48 hours Pregnancy/ Lactation

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>Amikacin 400 mg nebulized every 12 hours plus intravenous antibiotic(s) for 10 days | Drug: Amikacin<br>* 400 mg, nebulizer, every 12 hours, 10 days<br>* Other names: Amikin;|
| Placebo Comparator: placebo<br>nebulized placebo every 12 hours plus intravenous antibiotic(s)for 10 days. | Drug: Placebo<br>* placebo 4 ml, nebulizer, every 12 hours, 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cure rate | Cure rate = improvement/ no new infiltration of chest radiography plus 2/3 of the following: 1) No fever within 48 hours after end of the intervention 2) The reduction of secretion 3) The reduction of white blood cell | 10 days after end of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The reduction of pathogens | quantitative sputum cultures were measured every days for 10 days or no growth of organism. | 10 days after end of the intervention | 
| mortality rate | All causes of death during the intervention | at 28 days after end of the intervention | 
| duration of mechanical ventilation | number of days on mechanical ventilation | at 28 days after end of the intervention | 
| duration of ICU stay | number of ICU days | at 28 days after end of the intervention | 
| duration of hospitalization | number of days hospitalization | at 28 days after end of the intervention | 
| Safety of intervention drug | Any adverse events were recorded | at 28 days after end of the intervention |