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

Purpose

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.

Condition	Intervention	Phase
Pneumonia, Ventilator-Associated Pseudomonas Infections	Drug: azithromycin Drug: placebo	Phase II

MedlinePlus related topics:

Pneumonia

ChemIDplus related topics:

Azithromycin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

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

Further study details as provided by Anbics Management-Services Ag:

Primary Outcome Measures:

Occurrence of and time to Pseudomonas aeruginosa pneumonia [ Time Frame: daily ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

occurrence of and time to death [ Time Frame: daily ] [ Designated as safety issue: Yes ]
time to extubation [ Time Frame: daily ] [ Designated as safety issue: No ]
overall outcome [ Time Frame: daily ] [ Designated as safety issue: Yes ]
duration of hospitalization and ICU stay [ Time Frame: daily ] [ Designated as safety issue: No ]
occurrence of infections to other bacterial strains [ Time Frame: daily ] [ Designated as safety issue: Yes ]
cost assessment [ Time Frame: daily ] [ Designated as safety issue: No ]
demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa [ Time Frame: daily ] [ Designated as safety issue: No ]
determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics [ Time Frame: daily ] [ Designated as safety issue: Yes ]
determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin [ Time Frame: daily ] [ Designated as safety issue: Yes ]

Enrollment:	92
Study Start Date:	April 2003
Study Completion Date:	October 2005
Primary Completion Date:	October 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental azithromycin iv 300 mg/day	Drug: azithromycin 300 mg/day, IV from day 1 to 20
2: Placebo Comparator Placebo	Drug: placebo once per day, IV from day 1 to 20

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00610623

Locations


Belgium
	General Intensive Car Unit, Centre Hospitalier Universitaire de Liège
	Liège, Belgium, B-4000

Belgium, Louvain
	Intensive Care Unit, Clinique Saint-Pierre
	Ottignies, Louvain, Belgium, 1340

France
	Intensive Care Unit, Jean Minjoz University Hospital
	Besancon, France, 25030
	Intensive Car Unit, Calmette University Hospital of Lille
	Lille, France, 59037
	Medical-surgical intensive car unit, Dupuytren Teaching Hospital
	Limoges, France, 8700
	Medical Intensive Car Unit, Hospital Bichat
	Paris, France, 75018
	Surgical Intensive Car Unit; University Hospital Bichat
	Paris, France, 75018
	General Intensive Care Unit, Hospital Saint-Joseph
	Paris, France, 75674
	Medical Intensive Care Unit, Cochin Hospital
	Paris, France, 75679
	General Intensive Care Unit, Montauban City Hospital
	Montauban, France, 82013

Poland
	Intensive Care Unit, Wojewodzki Hospital
	Sosnowiec, Poland
	Intensive Care Unit, Central Hospital
	Warsaw, Poland
	Intensive Care Unit, Wojewodzki Hospital
	Krakow, Poland

Serbia and Montenegro
	Surgical Intensive Care Unit, Clinical Center of Serbia
	Belgrade, Serbia and Montenegro
	Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery
	Belgrade, Serbia and Montenegro

Spain
	Intensive Care Unit, San Dureta University Hospital
	Palma de Mallorca, Spain, 07014
	Intensive Care Unit, Hospital del Mar
	Barcelona, Spain, 08003
	Internal Medicine, Vall d'Hebron Hospital
	Barcelona, Spain, 08035
	Intensive Care Unit, Joan XXIII University Hospital
	Tarragona, Spain, 43007

Switzerland, Vaud
	Surgical and Medical Intensive Care Units, University Hospital Lausanne
	Lausanne, Vaud, Switzerland

Sponsors and Collaborators

Anbics Management-Services Ag

Swiss National Science Foundation

Investigators


Principal Investigator:	Christian Van Delden, MD	Service of Infectious Diseases, University Hospital Geneva, Switzerland

Study Chair:	Jean Carlet, MD	General Intensive Care Unit, Hospital Saint-Joseph, Paris, France

More Information

Responsible Party:	Service of Infectious Diseases, University Hospital Geneva ( Christian van Delden )
Study ID Numbers:	Anb006#2001
First Received:	January 24, 2008
Last Updated:	January 28, 2008
ClinicalTrials.gov Identifier:	NCT00610623
Health Authority:	Switzerland: Swissmedic

Keywords provided by Anbics Management-Services Ag:

Pseudomonas aeruginosa

Pneumonia

Ventilator-Associated

Quorum Sensing

Study placed in the following topic categories:

Bacterial Infections

Respiratory Tract Infections

Respiratory Tract Diseases

Pseudomonas Infections

Azithromycin

Lung Diseases

Pneumonia, Ventilator-Associated

Cross Infection

Pneumonia

Gram-Negative Bacterial Infections

Additional relevant MeSH terms:

Anti-Infective Agents

Anti-Bacterial Agents

Therapeutic Uses

Infection

Pharmacologic Actions

ClinicalTrials.gov processed this record on October 15, 2008

Sponsors and Collaborators:	Anbics Management-Services Ag Swiss National Science Foundation
Information provided by:	Anbics Management-Services Ag
ClinicalTrials.gov Identifier:	NCT00610623