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

Pneumonia, Ventilator-Associated Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00610623
• Other study ID #: Anb006#2001
• Status: Terminated
• Phase: Phase 2
• First received: January 24, 2008
• Last updated: January 28, 2008
• Start date: April 2003
• Est. completion date: October 2005

Study information

• Verified date: January 2008
• Source: Anbics Management-Services Ag
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: October 2005
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Pseudomonas Infections

Intervention

Drug:
• azithromycin
300 mg/day, IV from day 1 to 20
• placebo
once per day, IV from day 1 to 20

Locations

Country	Name	City	State
Belgium	General Intensive Car Unit, Centre Hospitalier Universitaire de Liège	Liège
Belgium	Intensive Care Unit, Clinique Saint-Pierre	Ottignies	Louvain
Former Serbia and Montenegro	Surgical Intensive Care Unit, Clinical Center of Serbia	Belgrade
Former Serbia and Montenegro	Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery	Belgrade
France	Intensive Care Unit, Jean Minjoz University Hospital	Besancon
France	Intensive Car Unit, Calmette University Hospital of Lille	Lille
France	Medical-surgical intensive car unit, Dupuytren Teaching Hospital	Limoges
France	General Intensive Care Unit, Montauban City Hospital	Montauban
France	General Intensive Care Unit, Hospital Saint-Joseph	Paris
France	Medical Intensive Car Unit, Hospital Bichat	Paris
France	Medical Intensive Care Unit, Cochin Hospital	Paris
France	Surgical Intensive Car Unit; University Hospital Bichat	Paris
Poland	Intensive Care Unit, Wojewodzki Hospital	Krakow
Poland	Intensive Care Unit, Wojewodzki Hospital	Sosnowiec
Poland	Intensive Care Unit, Central Hospital	Warsaw
Spain	Intensive Care Unit, Hospital del Mar	Barcelona
Spain	Internal Medicine, Vall d'Hebron Hospital	Barcelona
Spain	Intensive Care Unit, San Dureta University Hospital	Palma de Mallorca
Spain	Intensive Care Unit, Joan XXIII University Hospital	Tarragona
Switzerland	Surgical and Medical Intensive Care Units, University Hospital Lausanne	Lausanne	Vaud

Sponsors (2)

Lead Sponsor	Collaborator
Anbics Management-Services Ag	Swiss National Science Foundation

Countries where clinical trial is conducted

Belgium,  Former Serbia and Montenegro,  France,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of and time to Pseudomonas aeruginosa pneumonia		daily	No
Secondary	occurrence of and time to death		daily	Yes
Secondary	time to extubation		daily	No
Secondary	overall outcome		daily	Yes
Secondary	duration of hospitalization and ICU stay		daily	No
Secondary	occurrence of infections to other bacterial strains		daily	Yes
Secondary	cost assessment		daily	No
Secondary	demonstrate using in vitro and in vivo parameters that azithromycin can be used as a quorum-sensing blocker against P. aeruginosa		daily	No
Secondary	determine whether prolonged treatment with azithromycin may induce resistance to any of 11 anti-pseudomonal antibiotics		daily	Yes
Secondary	determine whether P. aeruginosa can develop resistance to the quorum-sensing effect of azithromycin		daily	Yes