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

NCT00610623 | Terminated Phase 2 DMC

• 1 other identifier: Anb006#2001
• Study Type: interventional
• Target: 92
• Locations: 6 countries
• Sites: 20

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.

Conditions

Pneumonia, Ventilator-Associated; Pseudomonas Infections

Keywords

Pseudomonas aeruginosa; Pneumonia; Ventilator-Associated; Quorum Sensing

Outcome Measures

Primary Outcomes (1)

• Occurrence of and time to Pseudomonas aeruginosa pneumonia

  daily

Secondary Outcomes (9)

• 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

Study Arms (2)

1

EXPERIMENTAL

azithromycin iv 300 mg/day

Drug: azithromycin

2

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

azithromycin DRUG

300 mg/day, IV from day 1 to 20

Also known as: Zithromax

1

placebo DRUG

once per day, IV from day 1 to 20

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Anbics Management-Services Ag: lead
• Swiss National Science Foundation: collaborator

Study Sites (20)

General Intensive Car Unit, Centre Hospitalier Universitaire de Liège

Liège, Liège, B-4000, Belgium

Location

Intensive Care Unit, Clinique Saint-Pierre

Ottignies, Louvain, 1340, Belgium

Location

Intensive Care Unit, Jean Minjoz University Hospital

Besançon, Besancon, 25030, France

Location

Intensive Car Unit, Calmette University Hospital of Lille

Lille, Lille, 59037, France

Location

Medical-surgical intensive car unit, Dupuytren Teaching Hospital

Limoges, Limoges, 8700, France

Location

General Intensive Care Unit, Montauban City Hospital

Montauban, Montauban, 82013, France

Location

Medical Intensive Car Unit, Hospital Bichat

Paris, Paris, 75018, France

Location

Surgical Intensive Car Unit; University Hospital Bichat

Paris, Paris, 75018, France

Location

General Intensive Care Unit, Hospital Saint-Joseph

Paris, Paris, 75674, France

Location

Medical Intensive Care Unit, Cochin Hospital

Paris, Paris, 75679, France

Location

Intensive Care Unit, Wojewodzki Hospital

Krakow, Poland

Location

Intensive Care Unit, Wojewodzki Hospital

Sosnowiec, Poland

Location

Intensive Care Unit, Central Hospital

Warsaw, Poland

Location

Surgical Intensive Care Unit, Clinical Center of Serbia, Institut of Neurosurgery

Belgrade, Serbia and Montenegro

Location

Surgical Intensive Care Unit, Clinical Center of Serbia

Belgrade, Serbia and Montenegro

Location

Intensive Care Unit, Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Internal Medicine, Vall d'Hebron Hospital

Barcelona, Barcelona, 08035, Spain

Location

Intensive Care Unit, Joan XXIII University Hospital

Tarragona, Tarragona, 43007, Spain

Location

Intensive Care Unit, San Dureta University Hospital

Palma de Mallorca, 07014, Spain

Location

Surgical and Medical Intensive Care Units, University Hospital Lausanne

Lausanne, Canton of Vaud, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 20463812 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pneumonia

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Christian Van Delden, MD

  Service of Infectious Diseases, University Hospital Geneva, Switzerland

  PRINCIPAL INVESTIGATOR

• Jean Carlet, MD

  General Intensive Care Unit, Hospital Saint-Joseph, Paris, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 24, 2008
• First Posted: February 8, 2008
• Study Start: April 1, 2003
• Primary Completion: October 1, 2005
• Study Completion: October 1, 2005
• Last Updated: February 8, 2008

Record last verified: 2008-01

Locations

SE (2); PL (3); FR (8); ES (4); BE (2); CH (1)