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Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia (AMIKINHAL)

Primary Purpose

Pneumonia, Ventilator-Associated

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Inhaled amikacin
Inhaled placebo
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pneumonia, Ventilator-Associated focused on measuring Prevention, inhaled amikacin, placebo

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Service de Réanimation Chirurgicale
  • Service de Réanimation Médicale - CH d'Angoulême
  • Service de Réanimation Polyvalente
  • Service de Réanimation Médicale - Hôpital Louis Mourier
  • Service de Réanimation
  • Service de Réanimation Médicale - CHD Les Oudairies
  • Service de Réanimation
  • Service de Réanimation Médicale - Hôpital La Croix-Rousse
  • Service de Réanimation Médicale
  • Service de Réanimation Médicale - Hôpital Pitié Salpêtrière
  • Service de Réanimation Médicale - CHU La Milétrie
  • Service de Réanimation Médicale
  • Service de Réanimation Médicale - CHU Pontchaillou
  • Service de Réanimation Médicale - CHU Rouen
  • Service de Réanimation Médicale - Hôpital Charles Nicolle
  • Service de Réanimation - NHC
  • Service de Réanimation Médicale - Hôpital de Hautepierre
  • Service de Réanimation médicale, Hôpital Trousseau

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Inhaled amikacin

Placebo

Arm Description

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.

Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.

Outcomes

Primary Outcome Measures

Incidence of a first VAP episode from randomization to day 28

Secondary Outcome Measures

Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis
Incidence of VAP due to Gram negative amikacin sensitive bacteria
Clinical pulmonary infection score evolution
Ventilator associated events incidence
Number of systemic antibiotics administered per day
Number of days with at least one administration of a systemic antibiotic
Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples
Incidence of acute kidney injury
Days spent on mechanical ventilation from randomization to day 90
Days from randomization to the first successful spontaneous breathing trial
Days spent in the intensive care unit and in the hospital
Day 90 mortality
Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples
Relative bacterial species composition of respiratory and digestive microbiota
Maximum serum Concentration
Maximum sputum Concentration
Area Under the Curve
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

Full Information

First Posted
May 2, 2017
Last Updated
November 4, 2022
Sponsor
University Hospital, Tours
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1. Study Identification

Unique Protocol Identification Number
NCT03149640
Brief Title
Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
Acronym
AMIKINHAL
Official Title
Double-blinded Multicenter Randomized Controlled Trial Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
July 19, 2017 (Actual)
Primary Completion Date
March 9, 2021 (Actual)
Study Completion Date
June 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Ventilator-Associated
Keywords
Prevention, inhaled amikacin, placebo

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
850 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inhaled amikacin
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.
Intervention Type
Drug
Intervention Name(s)
Inhaled amikacin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Inhaled placebo
Intervention Description
Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.
Primary Outcome Measure Information:
Title
Incidence of a first VAP episode from randomization to day 28
Time Frame
Patients will be followed from randomization to day 28
Secondary Outcome Measure Information:
Title
Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis
Time Frame
At randomization
Title
Incidence of VAP due to Gram negative amikacin sensitive bacteria
Time Frame
Patients will be followed from randomization to day 28
Title
Clinical pulmonary infection score evolution
Time Frame
Patients will be followed from randomization to day 28
Title
Ventilator associated events incidence
Time Frame
Patients will be followed from randomization to day 28
Title
Number of systemic antibiotics administered per day
Time Frame
Patients will be followed from randomization to day 28
Title
Number of days with at least one administration of a systemic antibiotic
Time Frame
Patients will be followed from randomization to day 28
Title
Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples
Time Frame
Patients will be followed from randomization to day 28
Title
Incidence of acute kidney injury
Time Frame
Patients will be followed from randomization to day 28
Title
Days spent on mechanical ventilation from randomization to day 90
Time Frame
Patients will be followed from randomization to day 90
Title
Days from randomization to the first successful spontaneous breathing trial
Time Frame
Days from randomization to day 90 max
Title
Days spent in the intensive care unit and in the hospital
Time Frame
Patients will be followed from randomization to discharge (day 90 max)
Title
Day 90 mortality
Time Frame
Day 90
Title
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
Title
Relative bacterial species composition of respiratory and digestive microbiota
Time Frame
Patients will be followed from randomization to day 28
Title
Maximum serum Concentration
Time Frame
Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Title
Maximum sputum Concentration
Time Frame
Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Title
Area Under the Curve
Time Frame
Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Title
To evaluate the effects on respiratory mechanics of nebulization of amikacin by evaluating the benefit balance / risk
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan EHRMANN, MD-PhD
Organizational Affiliation
University Hospital, Tours
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Réanimation Chirurgicale
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Service de Réanimation Médicale - CH d'Angoulême
City
Angoulême
ZIP/Postal Code
16959
Country
France
Facility Name
Service de Réanimation Polyvalente
City
Argenteuil
Country
France
Facility Name
Service de Réanimation Médicale - Hôpital Louis Mourier
City
Colombes
ZIP/Postal Code
92700
Country
France
Facility Name
Service de Réanimation
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Service de Réanimation Médicale - CHD Les Oudairies
City
La Roche-sur-Yon
ZIP/Postal Code
85025
Country
France
Facility Name
Service de Réanimation
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
Service de Réanimation Médicale - Hôpital La Croix-Rousse
City
Lyon
ZIP/Postal Code
69317
Country
France
Facility Name
Service de Réanimation Médicale
City
Orléans
ZIP/Postal Code
45100
Country
France
Facility Name
Service de Réanimation Médicale - Hôpital Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Service de Réanimation Médicale - CHU La Milétrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Service de Réanimation Médicale
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Service de Réanimation Médicale - CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Service de Réanimation Médicale - CHU Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Service de Réanimation Médicale - Hôpital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Service de Réanimation - NHC
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Service de Réanimation Médicale - Hôpital de Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Service de Réanimation médicale, Hôpital Trousseau
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34521664
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.
Results Reference
derived

Learn more about this trial

Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia

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