Azithromycin as a Quorum-Sensing Inhibitor for the Prevention of Pseudomonas Aeruginosa Ventilator-Associated Pneumonia

Study Overview
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Brief Summary
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The purpose of this study is to assess the clinical efficacy of azithromycin, used as a quorum-sensing blocker, when compared to placebo for preventing or delaying the occurrence of pneumonia in ventilated patients colonized with Pseudomonas aeruginosa.

Official Title
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Proof of Concept Study to Investigate the Impact of Azithromycin Administered iv Versus Placebo on the Prevention of Pneumonia in Ventilated Patients Colonized by Pseudomonas Aeruginosa

Conditions
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Pneumonia, Ventilator-Associated, Pseudomonas Infections

Intervention / Treatment
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* Drug: azithromycin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non pregnant female aged 18 to 75 years Patients hospitalized in ICU, under mechanically assisted ventilation expected to be mandatory for 3 days or more Reasonable survival chance within next few days with an Apache score 10-25 Tracheal aspirate found positive for P. aeruginosa The subject (or a close family member in case of incompetence) understands the procedure, agrees to participate, and is willing to give written informed consent Informed consent must be obtained for all subjects before enrollment in the study, by patient or by a close family member Exclusion Criteria: Poor prognosis as judged by Apache score II score >25 Pregnant female Grossly under-or overweight (BMI<18or >29) Ongoing therapy with a macrolide Known allergy to any macrolide Proven P. aeruginosa pneumonia Ongoing anti-pseudomonal therapy with a proven susceptible colonizing strain Anticipated short duration of mechanical ventilation (<3 days) Known drug interaction that could either decrease efficacy or raise safety concerns Severe hepatic failure (type C, score >10 on Child Pugh scale) Sick sinus syndrome or long QT syndrome Recent donation of blood or participation in another clinical trial within 3 months Any situation exposing the patient to higher risk or possibly confounding results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>azithromycin iv 300 mg/day | Drug: azithromycin<br>* 300 mg/day, IV from day 1 to 20<br>* Other names: Zithromax;|
| Placebo Comparator: 2<br>Placebo | Drug: placebo<br>* once per day, IV from day 1 to 20<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of and time to Pseudomonas aeruginosa pneumonia |  | daily | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of and time to death |  | daily | 
| time to extubation |  | daily | 
| overall outcome |  | daily | 
| duration of hospitalization and ICU stay |  | daily | 
| occurrence of infections to other bacterial strains |  | daily | 
| cost assessment |  | daily | 
| demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa |  | daily | 
| determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics |  | daily | 
| determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin |  | daily | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudomonas aeruginosa, Pneumonia, Ventilator-Associated, Quorum Sensing