Pneumonia, Ventilator-Associated, Pseudomonas Infections
Conditions
Keywords
Pseudomonas aeruginosa, Pneumonia, Ventilator-Associated, Quorum Sensing
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.
Interventions
DRUGazithromycin
300 mg/day, IV from day 1 to 20
DRUGplacebo
once per day, IV from day 1 to 20
Sponsors
Swiss National Science Foundation
Anbics Management-Services Ag
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of and time to Pseudomonas aeruginosa pneumonia | daily |
Secondary
| Measure | Time frame |
|---|---|
| time to extubation | daily |
| overall outcome | daily |
| duration of hospitalization and ICU stay | daily |
| occurrence of infections to other bacterial strains | daily |
| occurrence of and time to death | 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 |
| cost assessment | daily |
Countries
Belgium, France, Poland, Serbia and Montenegro, Spain, Switzerland
Outcome results
None listed