Back to resultsAzithromycin as a Quorum-Sensing Inhibitor for the Prevention of Pseudomonas Aeruginosa Ventilator-Associated Pneumonia
Primary Purpose
Pneumonia, Ventilator-Associated, Pseudomonas Infections
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
azithromycin
placebo
Sponsored by
About this trial
This is an interventional prevention trial for Pneumonia, Ventilator-Associated focused on measuring Pseudomonas aeruginosa, Pneumonia, Ventilator-Associated, Quorum Sensing
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
Sites / Locations
- Intensive Care Unit, Clinique Saint-Pierre
- General Intensive Car Unit, Centre Hospitalier Universitaire de Liège
- Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery
- Surgical Intensive Care Unit, Clinical Center of Serbia
- Intensive Care Unit, Jean Minjoz University Hospital
- Intensive Car Unit, Calmette University Hospital of Lille
- Medical-surgical intensive car unit, Dupuytren Teaching Hospital
- General Intensive Care Unit, Montauban City Hospital
- Medical Intensive Car Unit, Hospital Bichat
- Surgical Intensive Car Unit; University Hospital Bichat
- General Intensive Care Unit, Hospital Saint-Joseph
- Medical Intensive Care Unit, Cochin Hospital
- Intensive Care Unit, Wojewodzki Hospital
- Intensive Care Unit, Wojewodzki Hospital
- Intensive Care Unit, Central Hospital
- Intensive Care Unit, Hospital del Mar
- Internal Medicine, Vall d'Hebron Hospital
- Intensive Care Unit, San Dureta University Hospital
- Intensive Care Unit, Joan XXIII University Hospital
- Surgical and Medical Intensive Care Units, University Hospital Lausanne
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
azithromycin iv 300 mg/day
Placebo
Outcomes
Primary Outcome Measures
Occurrence of and time to Pseudomonas aeruginosa pneumonia
Secondary Outcome Measures
occurrence of and time to death
time to extubation
overall outcome
duration of hospitalization and ICU stay
occurrence of infections to other bacterial strains
cost assessment
demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa
determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics
determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin
Full Information
NCT ID
NCT00610623
First Posted
January 24, 2008
Last Updated
January 28, 2008
Sponsor
Anbics Management-Services Ag
Collaborators
Swiss National Science Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00610623
Brief Title
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
2. Study Status
Record Verification Date
January 2008
Overall Recruitment Status
Terminated
Why Stopped
The sponsor decided to stop the study prematurely because of financial issues
Study Start Date
April 2003 (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
October 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Anbics Management-Services Ag
Collaborators
Swiss National Science Foundation
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Ventilator-Associated, Pseudomonas Infections
Keywords
Pseudomonas aeruginosa, Pneumonia, Ventilator-Associated, Quorum Sensing
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
azithromycin iv 300 mg/day
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
300 mg/day, IV from day 1 to 20
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
once per day, IV from day 1 to 20
Primary Outcome Measure Information:
Title
Occurrence of and time to Pseudomonas aeruginosa pneumonia
Time Frame
daily
Secondary Outcome Measure Information:
Title
occurrence of and time to death
Time Frame
daily
Title
time to extubation
Time Frame
daily
Title
overall outcome
Time Frame
daily
Title
duration of hospitalization and ICU stay
Time Frame
daily
Title
occurrence of infections to other bacterial strains
Time Frame
daily
Title
cost assessment
Time Frame
daily
Title
demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa
Time Frame
daily
Title
determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics
Time Frame
daily
Title
determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin
Time Frame
daily
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Van Delden, MD
Organizational Affiliation
Service of Infectious Diseases, University Hospital Geneva, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jean Carlet, MD
Organizational Affiliation
General Intensive Care Unit, Hospital Saint-Joseph, Paris, France
Official's Role
Study Chair
Facility Information:
Facility Name
Intensive Care Unit, Clinique Saint-Pierre
City
Ottignies
State/Province
Louvain
ZIP/Postal Code
1340
Country
Belgium
Facility Name
General Intensive Car Unit, Centre Hospitalier Universitaire de Liège
City
Liège
ZIP/Postal Code
B-4000
Country
Belgium
Facility Name
Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery
City
Belgrade
Country
Former Serbia and Montenegro
Facility Name
Surgical Intensive Care Unit, Clinical Center of Serbia
City
Belgrade
Country
Former Serbia and Montenegro
Facility Name
Intensive Care Unit, Jean Minjoz University Hospital
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Intensive Car Unit, Calmette University Hospital of Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Medical-surgical intensive car unit, Dupuytren Teaching Hospital
City
Limoges
ZIP/Postal Code
8700
Country
France
Facility Name
General Intensive Care Unit, Montauban City Hospital
City
Montauban
ZIP/Postal Code
82013
Country
France
Facility Name
Medical Intensive Car Unit, Hospital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Surgical Intensive Car Unit; University Hospital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
General Intensive Care Unit, Hospital Saint-Joseph
City
Paris
ZIP/Postal Code
75674
Country
France
Facility Name
Medical Intensive Care Unit, Cochin Hospital
City
Paris
ZIP/Postal Code
75679
Country
France
Facility Name
Intensive Care Unit, Wojewodzki Hospital
City
Krakow
Country
Poland
Facility Name
Intensive Care Unit, Wojewodzki Hospital
City
Sosnowiec
Country
Poland
Facility Name
Intensive Care Unit, Central Hospital
City
Warsaw
Country
Poland
Facility Name
Intensive Care Unit, Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Internal Medicine, Vall d'Hebron Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Intensive Care Unit, San Dureta University Hospital
City
Palma de Mallorca
ZIP/Postal Code
07014
Country
Spain
Facility Name
Intensive Care Unit, Joan XXIII University Hospital
City
Tarragona
ZIP/Postal Code
43007
Country
Spain
Facility Name
Surgical and Medical Intensive Care Units, University Hospital Lausanne
City
Lausanne
State/Province
Vaud
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
20463812
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.
Results Reference
derived
Learn more about this trial
Azithromycin as a Quorum-Sensing Inhibitor for the Prevention of Pseudomonas Aeruginosa Ventilator-Associated Pneumonia
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