Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia

Pneumonia, Ventilator-Associated Clinical Trial

— AMIKINHAL  

Official title:

Double-blinded Multicenter Randomized Controlled Trial Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03149640
• Other study ID #: PHRN15-SE / AMIKINHAL
• Status: Completed
• Phase: Phase 3
• Start date: July 19, 2017
• Est. completion date: June 17, 2021

Study information

• Verified date: November 2022
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: June 17, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated

Intervention

Drug:
• Inhaled amikacin
Once a day, inhaled amikacin at day 4, day 5 and day 6 of invasive mechanical ventilation: 20 mg/kg of ideal body weight, maximum 2 g per day.
• Inhaled placebo
Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.

Locations

Country	Name	City	State
France	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	Service de Réanimation Médicale	Poitiers
France	Service de Réanimation Médicale - CHU La Milétrie	Poitiers
France	Service de Réanimation Médicale - CHU Pontchaillou	Rennes
France	Service de Réanimation Médicale - CHU Rouen	Rouen
France	Service de Réanimation Médicale - Hôpital Charles Nicolle	Rouen
France	Service de Réanimation - NHC	Strasbourg
France	Service de Réanimation Médicale - Hôpital de Hautepierre	Strasbourg
France	Service de Réanimation médicale, Hôpital Trousseau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of a first VAP episode from randomization to day 28		Patients will be followed from randomization to day 28
Secondary	Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis		At randomization
Secondary	Incidence of VAP due to Gram negative amikacin sensitive bacteria		Patients will be followed from randomization to day 28
Secondary	Clinical pulmonary infection score evolution		Patients will be followed from randomization to day 28
Secondary	Ventilator associated events incidence		Patients will be followed from randomization to day 28
Secondary	Number of systemic antibiotics administered per day		Patients will be followed from randomization to day 28
Secondary	Number of days with at least one administration of a systemic antibiotic		Patients will be followed from randomization to day 28
Secondary	Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples		Patients will be followed from randomization to day 28
Secondary	Incidence of acute kidney injury		Patients will be followed from randomization to day 28
Secondary	Days spent on mechanical ventilation from randomization to day 90		Patients will be followed from randomization to day 90
Secondary	Days from randomization to the first successful spontaneous breathing trial		Days from randomization to day 90 max
Secondary	Days spent in the intensive care unit and in the hospital		Patients will be followed from randomization to discharge (day 90 max)
Secondary	Day 90 mortality		Day 90
Secondary	Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples		Day 28
Secondary	Relative bacterial species composition of respiratory and digestive microbiota		Patients will be followed from randomization to day 28
Secondary	Maximum serum Concentration		Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Secondary	Maximum sputum Concentration		Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Secondary	Area Under the Curve		Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Secondary	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	Measurements at 8 hours, 12 hours and 24 hours after the end of nebulization