Clinical trial NCT03149640: Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
Official title: Double-blinded Multicenter Randomized Controlled Trial Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Ventilator-Associated
Keywords: Prevention
inhaled amikacin
placebo
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2017-05-11
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of a first VAP episode from randomization to day 28
timeFrame: Patients will be followed from randomization to day 28
Secondary outcomes:
measure: Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis
timeFrame: At randomization
measure: Incidence of VAP due to Gram negative amikacin sensitive bacteria
timeFrame: Patients will be followed from randomization to day 28
measure: Clinical pulmonary infection score evolution
timeFrame: Patients will be followed from randomization to day 28
measure: Ventilator associated events incidence
timeFrame: Patients will be followed from randomization to day 28
measure: Number of systemic antibiotics administered per day
timeFrame: Patients will be followed from randomization to day 28
measure: Number of days with at least one administration of a systemic antibiotic
timeFrame: Patients will be followed from randomization to day 28
measure: Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples
timeFrame: Patients will be followed from randomization to day 28
measure: Incidence of acute kidney injury
timeFrame: Patients will be followed from randomization to day 28
measure: Days spent on mechanical ventilation from randomization to day 90
timeFrame: Patients will be followed from randomization to day 90
measure: Days from randomization to the first successful spontaneous breathing trial
timeFrame: Days from randomization to day 90 max
measure: Days spent in the intensive care unit and in the hospital
timeFrame: Patients will be followed from randomization to discharge (day 90 max)
measure: Day 90 mortality
timeFrame: Day 90
measure: Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples
timeFrame: Day 28
measure: Relative bacterial species composition of respiratory and digestive microbiota
timeFrame: Patients will be followed from randomization to day 28
measure: Maximum serum Concentration
timeFrame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
measure: Maximum sputum Concentration
timeFrame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
measure: Area Under the Curve
timeFrame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
measure: To evaluate the effects on respiratory mechanics of nebulization of amikacin by evaluating the benefit balance / risk
timeFrame: Measurements at 8 hours, 12 hours and 24 hours after the end of nebulization
Other outcomes:
Locations:
city: Angers
country: France
facility: Service de Réanimation Chirurgicale
city: Angoulême
country: France
facility: Service de Réanimation Médicale - CH d'Angoulême
city: Argenteuil
country: France
facility: Service de Réanimation Polyvalente
city: Colombes
country: France
facility: Service de Réanimation Médicale - Hôpital Louis Mourier
city: Dijon
country: France
facility: Service de Réanimation
city: La Roche-sur-Yon
country: France
facility: Service de Réanimation Médicale - CHD Les Oudairies
city: Le Mans
country: France
facility: Service de Réanimation
city: Lyon
country: France
facility: Service de Réanimation Médicale - Hôpital La Croix-Rousse
city: Orléans
country: France
facility: Service de Réanimation Médicale
city: Paris
country: France
facility: Service de Réanimation Médicale - Hôpital Pitié Salpêtrière
city: Poitiers
country: France
facility: Service de Réanimation Médicale - CHU La Milétrie
city: Poitiers
country: France
facility: Service de Réanimation Médicale
city: Rennes
country: France
facility: Service de Réanimation Médicale - CHU Pontchaillou
city: Rouen
country: France
facility: Service de Réanimation Médicale - CHU Rouen
city: Rouen
country: France
facility: Service de Réanimation Médicale - Hôpital Charles Nicolle
city: Strasbourg
country: France
facility: Service de Réanimation - NHC
city: Strasbourg
country: France
facility: Service de Réanimation Médicale - Hôpital de Hautepierre
city: Tours
country: France
facility: Service de Réanimation médicale, Hôpital Trousseau
Study officials:
affiliation: University Hospital, Tours
name: Stephan EHRMANN, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tavernier E, Barbier F, Meziani F, Quenot JP, Herbrecht JE, Landais M, Roux D, Seguin P, Schnell D, Veinstein A, Veber B, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Dahyot-Fizelier C, Plantefeve G, Nay MA, Merdji H, Andreu P, Vecellio L, Muller G, Cabrera M, Le Pennec D, Respaud R, Lanotte P, Gregoire N, Leclerc M, Helms J, Boulain T, Lacherade JC, Ehrmann S; REVA network and the CRICS-TRIGGESEP F-CRIN network. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol. BMJ Open. 2021 Sep 14;11(9):e048591. doi: 10.1136/bmjopen-2020-048591.