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

Sponsor

Anbics Management-Services Ag (Industry)

Overall Status

Terminated

CT.gov ID

NCT00610623

Collaborator

Swiss National Science Foundation (Other)

Enrollment

Locations

Arms

Duration (Months)

4.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Ventilator-Associated Pseudomonas Infections	Drug: azithromycin Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Oct 1, 2005

Actual Study Completion Date :

Oct 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 azithromycin iv 300 mg/day	Drug: azithromycin 300 mg/day, IV from day 1 to 20 Other Names: Zithromax
Placebo Comparator: 2 Placebo	Drug: placebo once per day, IV from day 1 to 20

Arm

Intervention/Treatment

Experimental: 1

azithromycin iv 300 mg/day

Drug: azithromycin

300 mg/day, IV from day 1 to 20

Other Names:

Zithromax

Placebo Comparator: 2

Placebo

Drug: placebo

once per day, IV from day 1 to 20

Outcome Measures

Primary Outcome Measures

Occurrence of and time to Pseudomonas aeruginosa pneumonia [daily]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Intensive Care Unit, Clinique Saint-Pierre	Ottignies	Louvain	Belgium	1340
2	General Intensive Car Unit, Centre Hospitalier Universitaire de Liège	Liège		Belgium	B-4000
3	Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery	Belgrade		Former Serbia and Montenegro
4	Surgical Intensive Care Unit, Clinical Center of Serbia	Belgrade		Former Serbia and Montenegro
5	Intensive Care Unit, Jean Minjoz University Hospital	Besancon		France	25030
6	Intensive Car Unit, Calmette University Hospital of Lille	Lille		France	59037
7	Medical-surgical intensive car unit, Dupuytren Teaching Hospital	Limoges		France	8700
8	General Intensive Care Unit, Montauban City Hospital	Montauban		France	82013
9	Medical Intensive Car Unit, Hospital Bichat	Paris		France	75018
10	Surgical Intensive Car Unit; University Hospital Bichat	Paris		France	75018
11	General Intensive Care Unit, Hospital Saint-Joseph	Paris		France	75674
12	Medical Intensive Care Unit, Cochin Hospital	Paris		France	75679
13	Intensive Care Unit, Wojewodzki Hospital	Krakow		Poland
14	Intensive Care Unit, Wojewodzki Hospital	Sosnowiec		Poland
15	Intensive Care Unit, Central Hospital	Warsaw		Poland
16	Intensive Care Unit, Hospital del Mar	Barcelona		Spain	08003
17	Internal Medicine, Vall d'Hebron Hospital	Barcelona		Spain	08035
18	Intensive Care Unit, San Dureta University Hospital	Palma de Mallorca		Spain	07014
19	Intensive Care Unit, Joan XXIII University Hospital	Tarragona		Spain	43007
20	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