Clinical trial NCT00610623: Azithromycin as a Quorum-Sensing Inhibitor for the Prevention of Pseudomonas Aeruginosa Ventilator-Associated Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pneumonia, Ventilator-Associated
Pseudomonas Infections
Keywords: Pseudomonas aeruginosa
Pneumonia
Ventilator-Associated
Quorum Sensing
Lead sponsor: Anbics Management-Services Ag
Sponsor class: INDUSTRY
Collaborators: name: Swiss National Science Foundation
First posted: 2008-02-08
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of and time to Pseudomonas aeruginosa pneumonia
timeFrame: daily
Secondary outcomes:
measure: occurrence of and time to death
timeFrame: daily
measure: time to extubation
timeFrame: daily
measure: overall outcome
timeFrame: daily
measure: duration of hospitalization and ICU stay
timeFrame: daily
measure: occurrence of infections to other bacterial strains
timeFrame: daily
measure: cost assessment
timeFrame: daily
measure: demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa
timeFrame: daily
measure: determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics
timeFrame: daily
measure: determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin
timeFrame: daily
Other outcomes:
Locations:
city: Ottignies
country: Belgium
facility: Intensive Care Unit, Clinique Saint-Pierre
state: Louvain
city: Liège
country: Belgium
facility: General Intensive Car Unit, Centre Hospitalier Universitaire de Liège
city: Belgrade
country: Former Serbia and Montenegro
facility: Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery
city: Belgrade
country: Former Serbia and Montenegro
facility: Surgical Intensive Care Unit, Clinical Center of Serbia
city: Besancon
country: France
facility: Intensive Care Unit, Jean Minjoz University Hospital
city: Lille
country: France
facility: Intensive Car Unit, Calmette University Hospital of Lille
city: Limoges
country: France
facility: Medical-surgical intensive car unit, Dupuytren Teaching Hospital
city: Montauban
country: France
facility: General Intensive Care Unit, Montauban City Hospital
city: Paris
country: France
facility: Medical Intensive Car Unit, Hospital Bichat
city: Paris
country: France
facility: Surgical Intensive Car Unit; University Hospital Bichat
city: Paris
country: France
facility: General Intensive Care Unit, Hospital Saint-Joseph
city: Paris
country: France
facility: Medical Intensive Care Unit, Cochin Hospital
city: Krakow
country: Poland
facility: Intensive Care Unit, Wojewodzki Hospital
city: Sosnowiec
country: Poland
facility: Intensive Care Unit, Wojewodzki Hospital
city: Warsaw
country: Poland
facility: Intensive Care Unit, Central Hospital
city: Barcelona
country: Spain
facility: Intensive Care Unit, Hospital del Mar
city: Barcelona
country: Spain
facility: Internal Medicine, Vall d'Hebron Hospital
city: Palma de Mallorca
country: Spain
facility: Intensive Care Unit, San Dureta University Hospital
city: Tarragona
country: Spain
facility: Intensive Care Unit, Joan XXIII University Hospital
city: Lausanne
country: Switzerland
facility: Surgical and Medical Intensive Care Units, University Hospital Lausanne
state: Vaud
Study officials:
affiliation: Service of Infectious Diseases, University Hospital Geneva, Switzerland
name: Christian Van Delden, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General Intensive Care Unit, Hospital Saint-Joseph, Paris, France
name: Jean Carlet, MD
role: STUDY_CHAIR
References:
citation: Kohler T, Perron GG, Buckling A, van Delden C. Quorum sensing inhibition selects for virulence and cooperation in Pseudomonas aeruginosa. PLoS Pathog. 2010 May 6;6(5):e1000883. doi: 10.1371/journal.ppat.1000883.