Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia

University Hospital, Tours850 enrolled

Overview

The objective of the study is to prove that after the third day of invasive mechanical ventilation a three-day course of inhaled amikacin reduces the incidence of subsequent VAP. Parallel two group double blind randomized controlled clinical trial. Individual randomization, performed on day 4 of invasive mechanical ventilation, will be stratified on centre in order to account for variations in VAP prevention bundle implementation and use of systemic antibiotics the day of randomization. Patients will be treated three consecutive days with inhaled amikacin or placebo. Patients will be followed up daily in the intensive care unit for the occurrence of VAP according to international guidelines until day 28.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

850

Conditions

Pneumonia, Ventilator-Associated

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years the day of inclusion * Mechanical ventilation through an endotracheal tube for more than three consecutive days (72h) * Written informed consent of the patient or a proxy * Patients covered by or having the rights to French social security * Negative pregnancy test, at the time of inclusion, in women of childbearing potential Exclusion Criteria: * Suspicion or confirmed VAP the day of inclusion * Clinical indication for systemic aminoglycoside therapy the day of inclusion : as deemed necessary by the clinician in charge * Stage 2 or 3 KDIGO\* classification acute kidney injury the day of inclusion excepted in patients undergoing renal replacement therapy * Chronic kidney failure : baseline glomerular filtration lower than 30 mL/min * Patient scheduled for extubation within the next 24h * Patient ventilated through an endotracheal tube for more than four consecutive days before inclusion (96h) * Patient ventilated through a tracheostomy * Patients allergic to aminoglycosides * Myasthenia gravis * Known pregnant women at the time of inclusion and lactating patients * Known guardianship or trusteeship at the time of inclusion * Patients previously included in this study

Locations (18)

Service de Réanimation Chirurgicale

Angers, France

Service de Réanimation Médicale - CH d'Angoulême

Angoulême, France

Service de Réanimation Polyvalente

Argenteuil, France

Service de Réanimation Médicale - Hôpital Louis Mourier

Colombes, France

Service de Réanimation

Dijon, France

Service de Réanimation Médicale - CHD Les Oudairies

La Roche-sur-Yon, France

Service de Réanimation

Le Mans, France

Service de Réanimation Médicale - Hôpital La Croix-Rousse

Lyon, France

Service de Réanimation Médicale

Orléans, France

Service de Réanimation Médicale - Hôpital Pitié Salpêtrière

Paris, France

...and 8 more locations

Outcomes

Primary Outcomes

Incidence of a first VAP episode from randomization to day 28

Time frame: Patients will be followed from randomization to day 28

Secondary Outcomes

Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis

Time frame: At randomization

Incidence of VAP due to Gram negative amikacin sensitive bacteria

Time frame: Patients will be followed from randomization to day 28

Clinical pulmonary infection score evolution

Time frame: Patients will be followed from randomization to day 28

Ventilator associated events incidence

Time frame: Patients will be followed from randomization to day 28

Number of systemic antibiotics administered per day

Time frame: Patients will be followed from randomization to day 28

Number of days with at least one administration of a systemic antibiotic

Time frame: Patients will be followed from randomization to day 28

Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples

Time frame: Patients will be followed from randomization to day 28

Incidence of acute kidney injury

Time frame: Patients will be followed from randomization to day 28

Days spent on mechanical ventilation from randomization to day 90

Time frame: Patients will be followed from randomization to day 90

Days from randomization to the first successful spontaneous breathing trial

Time frame: Days from randomization to day 90 max

Days spent in the intensive care unit and in the hospital

Time frame: Patients will be followed from randomization to discharge (day 90 max)

Day 90 mortality

Time frame: Day 90

Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples

Time frame: Day 28

Relative bacterial species composition of respiratory and digestive microbiota

Time frame: Patients will be followed from randomization to day 28

Maximum serum Concentration

Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24

Maximum sputum Concentration

Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24

Area Under the Curve

Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24

To evaluate the effects on respiratory mechanics of nebulization of amikacin by evaluating the benefit balance / risk

benefit : Improvement of respiratory mechanics by pharmacological effect risk : Degradation of respiratory mechanics by bronchospastic secondary effect, drug deposition in the intubation probe

Time frame: Measurements at 8 hours, 12 hours and 24 hours after the end of nebulization