Intravenous Clarithromycin in Septic Syndrome

Study Overview
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Brief Summary
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The aim of this clinical trial is to clarify the clinical efficacy of clarithromycin as immunotherapy for the management of septic syndrome by ventilator-associated pneumonia.

Detailed Description
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The rationale of the trial is based on the favorable results of experimental studies of sepsis by multidrug-resistant Pseudomonas aeruginosa and by susceptible Escherichia coli in rabbits where clarithromycin was administered intravenously. Data from these latter studies suggest that administration of clarithromycin extended survival and attenuated systemic inflammatory response. Their major endpoint was successful immunotherapy achieved when clarithromycin was administered on presentation of symptoms of sepsis-induced pulmonary edema; on the contrary, former clinical trials for immunotherapies of sepsis were based on animal studies where the under evolution immunomodulator was administered before bacterial challenge. The efficacy of administration of clarithromycin upon presentation of septic syndrome in animal studies, renders its application promising in the clinical field.

Official Title
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Clarithromycin as Immunomodulatory Therapy for the Management of Septic Syndrome by Ventilator-Associated Pneumonia

Conditions
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Sepsis, Ventilator Associated Pneumonia

Intervention / Treatment
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* Drug: Intravenous Clarithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent provided by first or second degree relatives; intubation and mechanical ventilation at least 48 hours prior to enrolment; c) age of patients equal to or more than 18 years; d) diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis Exclusion Criteria: neutropenia, defined as less than 500 neutrophils/mm3; HIV infection; oral intake of corticosteroids at a dose equal to or higher than 1mg/kg equivalent prednisone for a period greater than one month; administration of drotrecogin alpha the last five days prior to enrolment; and e) atrioventricular block of second or third degree.

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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Intravenous Clarithromycin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimation of crude mortality by any reason of each study group |  |  | 
| Estimation of attributable mortality by VAP of each study group |  |  | 
| 7-day mortality rate of each group |  |  | 
| 28-mortality rate of each group |  |  | 
| Rate of progression to multiple organ failure and septic shock (and number of failing organs) of each study group |  |  | 
| Time to progression to multiple organ failure and septic shock of each study group |  |  | 
| Days of resolution of VAP |  |  | 
| Days in ICU after diagnosis of VAP |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of administration of clarithromycin on systemic inflammatory response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clarithromycin, sepsis, immunomodulation