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Inhaled Amikacin Versus Placebo in Patients With Ventilator-associated Tracheobronchitis (AMIVAT)

18. juni 2026 opdateret af: University Hospital, Tours

A Multicentre, Double-blind, Randomized Controlled Trial of Inhaled Amikacin Versus Placebo in Critically Ill Patients With Ventilator-associated Tracheobronchitis

The primary objective of the AMIVAT trial is to assess whether a 5-day course of inhaled amikacin, compared to placebo, reduces the incidence of progression to ventilator-associated pneumonia (VAP) at day 28 in intensive care unit (ICU) patients with ventilator-associated tracheobronchitis (VAT). Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

VAT will be defined using the following criteria: (i) duration of mechanical ventilation > 48 hours, (ii) purulent tracheobronchial secretions, (iii) no new or progressive persistent pulmonary infiltrate on chest X-ray, and (iv) bacterial growth on endotracheal aspirate (ETA) ≥10.5 colony-forming unit (CFU)/mL or on bronchoalveolar lavage ≥10.4 CFU/mL or on plugging telescopic catheter ≥10.3 CFU/mL. Inclusion and randomization will be performed after written informed consent, as soon as inclusion criteria are met, within 24 hours after VAT suspicion (ETA sampling) whenever possible. Patients in the experimental group will receive inhaled amikacin (once daily, 20 mg/kg of predicted body weight with a maximum of 2 grams) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer). Patients in the control group will receive inhaled placebo (NaCl 0.9%, once daily) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer). Nebulization will be performed according to a standardized procedure using a vibrating mesh nebulizer (Aerogen Solo, Aerogen, Galway, Ireland). A bedside checklist will be used to ensure optimal implementation practice. All staff involved in nebulization will be trained prior to their study involvement. The systemic diffusion and pharmacokinetics of inhaled amikacin will be assessed through measurement of peak and residual blood concentrations in a pre-planned subsample of patients. Study treatment will be discontinued before the 5th administration in the following cases: (i) documented acquired amikacin resistance in at least one pathogen responsible for VAT, (ii) occurrence of VAP before Day 5, (iii) occurrence of AKI stage 2 or 3 of the KDIGO classification before Day 5 (except for patients receiving renal replacement therapy), (iv) clinical indication for mandatory IV aminoglycoside therapy (amikacin, gentamicin, tobramycin) before Day 5, (v) extubation before Day 5, (vi) unexpected SAE deemed related to the IP and/or a patient's clinical condition that requires suspension of the treatment according to the local investigator. Patients will be followed-up until Day 28 for the primary study endpoint and up to Day 90 for certain secondary study endpoints (Day-90 mortality, and day-90 health-related quality of life [HRQoL] in survivors).

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

250

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Frankrig
      • Angers, Frankrig, 49933
        • 06 - ANGERS - Intensive care, University Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Tchamba Achille KOUATCHET
      • Argenteuil, Frankrig
        • 04 - ARGENTEUIL - Intensive care, University Hospital
        • Ledende efterforsker:
          • Gaëtan PLANTEFEVE
        • Kontakt:
      • Blois, Frankrig
        • 11 - BLOIS, Intensive care, Hospital
        • Ledende efterforsker:
          • Julien GROUILLE
        • Kontakt:
      • Bourg-en-Bresse, Frankrig, 01012
        • 09 - BOURG-EN-BRESSE, Intensive care, Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Adrien ROBINE
      • Créteil, Frankrig, 94010
        • 10 - HENRI MONDOR, Intensive care, University Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Pierre BAY
      • Dieppe, Frankrig, 76202
        • 07 - DIEPPE - Intensive care, University Hospital
        • Ledende efterforsker:
          • Pierre-Louis DECLERCQ
        • Kontakt:
      • Dijon, Frankrig, 21000
        • 08 - DIJON - Intensive care, University Hospital
        • Ledende efterforsker:
          • Jean-Pierre QUENOT
        • Kontakt:
      • Dreux, Frankrig, 28100
        • 12 - DREUX, Intensive care, Hospital
      • Le Chesnay, Frankrig, 78150
        • 14 - VERSAILLES, Intensive care, Hospital
        • Ledende efterforsker:
          • Alexis FERRE
        • Kontakt:
      • Le Mans, Frankrig, 72037
        • 05 - LE MANS - Intensive care, University Hospital
        • Ledende efterforsker:
          • Mickaël LANDAIS
        • Kontakt:
      • Lyon, Frankrig, 69437
        • 15 - LYON EH, Intensive care, University Hospital
        • Ledende efterforsker:
          • Laurent ARGAUD
        • Kontakt:
      • Orléans, Frankrig, 45000
        • 01 - ORLEANS - Intensive care, University Hospital
        • Ledende efterforsker:
          • François BARBIER
        • Kontakt:
      • Paris, Frankrig, 32700
        • 17 - LOUIS MOURIER, Intensive care, University Hospital
        • Ledende efterforsker:
          • Damien ROUX
        • Kontakt:
      • Paris, Frankrig
        • 13 - BICHAT, Intensive care, Univerity Hospital
        • Ledende efterforsker:
          • Jean-François TIMSIT
        • Kontakt:
      • Pierre-Bénite, Frankrig, 69495
        • 16 - LYON SUD, Intensive care, University Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Donatien DE MARIGNAN
      • Strasbourg, Frankrig, 67091
        • 03 - STRASBOURG - Intensive care, University Hospital
        • Ledende efterforsker:
          • Julien DEMISELLE
        • Kontakt:
      • Tours, Frankrig, 37044
        • 02 - TOURS - Intensive care, University Hospital
        • Ledende efterforsker:
          • Stephan EHRMANN
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion criteria:

  • Age ≥ 18 years
  • Admission to a participating intensive care unit (ICU)
  • Invasive mechanical ventilation > 48 hours
  • First episode of ventilator-associated tracheobronchitis during the ICU stay defined using the following criteria: (i) purulent tracheobronchial secretions, (iii) no new or progressive persistent pulmonary infiltrate on chest X-ray, and (iv) bacterial growth on endotracheal aspirate ≥10.5 colony-forming unit (CFU)/mL or on bronchoalveolar lavage ≥10.4 CFU/mL or on plugging telescopic catheter ≥10.3 CFU/mL
  • Coverage by the French health insurance system (Social Security)
  • Written informed consent obtained from the patient, or, if the patient is not able to give written consent, from his or her legally designated representative (trusted person designated by the patient or, failing that, a family member) or, failing that, inclusion performed by the investigator within the therapeutic window (in such cases, informed consent will be sought by the investigator from the patient, or his or her legally designated representative, whichever is sooner). In all cases, the patient's written informed consent will be obtained as soon as possible.
  • For woman of childbearing potential: negative pregnancy test result at the time of inclusion

Exclusion criteria:

  • Previous ventilator-associated pneumonia due to the pathogens responsible for ventilator-associated tracheobronchitis during the same ICU stay
  • On-going antimicrobial therapy fpr ventilator-associated pneumonia
  • Ventilator-associated tracheobronchitis due to pathogens with intrinsic amikacin resistance (e.g. Stenotrophomonas maltophilia)
  • On-going therapy with intravenous amikacin or another aminoglycoside
  • Acute kidney injury stage 2 or 3 of the Kidney Disease Improving Global Outcomes (KDIGO) classification and/or advanced chronic kidney failure (glomerular filtration rate <30 mL/min), except in patients under renal replacement therapy
  • Grade B or C cirrhosis (Child-Pugh classification)
  • Scheduled extubation within 24h
  • Prior tracheotomy
  • Administration of inhaled antibiotics within the 7 preceding days
  • Known hypersensitivity to amikacin, another aminoglycoside, or any of the excipients
  • Myasthenia gravis
  • Contraindication to nebulization
  • On-going treatment with ataluren
  • Persons covered by articles L1121-5 to L1121-8 of the French Public Health Code (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship).
  • Moribund patient
  • End-of-life decision
  • Previous inclusion in the present study
  • Participation to another interventional study
  • Inability of the patient, or the person providing consent, to understand all aspects of the research
  • Patient being a relative of the investigator or a relative of someone from the team directly involved in the trial, including doctors and pharmacists

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Inhaled amikacin
Medicin: Optimized and protocolized nebulization procedure.
Patients in the experimental group will receive inhaled amikacin (once daily, 20 mg/kg of predicted body weight with a maximum of 2 grams) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer).
Medicin: Optimized and protocolized nebulization procedure.
Patients in the control group will receive inhaled placebo (NaCl 0.9%, once daily) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer).
Placebo komparator: Inhaled NaCl 0.9%
Medicin: Optimized and protocolized nebulization procedure.
Patients in the experimental group will receive inhaled amikacin (once daily, 20 mg/kg of predicted body weight with a maximum of 2 grams) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer).
Medicin: Optimized and protocolized nebulization procedure.
Patients in the control group will receive inhaled placebo (NaCl 0.9%, once daily) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer).

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 28
Tidsramme: From randomization to day 28
Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT
From randomization to day 28

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 7
Tidsramme: From randomization to day 7
Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT
From randomization to day 7
Overall incidence of a first ventilator-associated pneumonia episode (all pathogens) at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
Overall incidence of a first ventilator-associated pneumonia episode due to multidrug-resistant bacteria at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
Time to resolution of clinical signs of ventilator-associated tracheobronchitis
Tidsramme: From randomization to day 28
Purulent tracheal aspirates, plus leukocytosis or leukopenia and/or fever or hypothermia if present at randomization
From randomization to day 28
Proportion of patients with persistence of the pathogens responsible for ventilator-associated tracheobronchitis on endotracheal aspirate at day 7
Tidsramme: Day 7
Day 7
Total duration of mechanical ventilation
Tidsramme: From randomization to day 90
Number of days with mechanical ventilation
From randomization to day 90
Number of ventilator-free days at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
The number of days with systemic antibiotics at Day 28
Tidsramme: From randomization to day 28
i.e., intravenous and/or enteral administration
From randomization to day 28
Number of defined daily doses of systemic antibiotics at day 28
Tidsramme: From randomization to day 28
i.e., intravenous and/or enteral administration
From randomization to day 28
Incidence of intensive care unit-acquired intestinal colonization with multidrug-resistant bacteria at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
Overall incidence of Intensive care unit-acquired infection due to multidrug-resistant bacteria at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
Lenght of stay in the intensive care unit
Tidsramme: From randomization to day 90
From randomization to day 90
Lenght of hospital stay
Tidsramme: From randomization to day 90
From randomization to day 90
All-cause mortality at day 28
Tidsramme: From randomization to day 28
From randomization to day 28
All-cause mortality at day 90
Tidsramme: From randomization to day 90
From randomization to day 90
Health-related quality of life at day 90
Tidsramme: Day 90
EuroQuol-5 Dimensions-5 Levels standardised questionnaire (5Q-5D-5L). Health state will be converted into a utility values using the appropriate weight in each country. Health state EQ-5D values range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility.
Day 90
Incidence of acute kidney injury at day 28
Tidsramme: From randomization to day 28
Safety analysis
From randomization to day 28
Occurrence of respiratory adverse events related to amikacin nebulization
Tidsramme: From randomization to day 90
Safety analysis
From randomization to day 90
Peak serum amikacin concentration 1 hour after inhaled study-drug nebulization
Tidsramme: At Day 1, Day 3 and Day 5.
Pre-planned subsample. Blood samples will be collected in 50 selected patients, 25 per arm to preserve blinding For each patient included in this substudy, one sample will be collected 1 hour after the preceding nebulization to measure the peak serum amikacin concentration.
At Day 1, Day 3 and Day 5.
Trough serum amikacin concentration 24 hours after inhaled study-drug nebulization.
Tidsramme: At Day 1, Day 3 and Day 5.
Blood samples will be collected in 50 selected patients, 25 per arm to preserve blinding. For each patient included in this substudy, two samples will be collected 24 hours after the preceding nebulization to measure trough serum amikacin concentrations, for a total of 3 samples per patient.
At Day 1, Day 3 and Day 5.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University Hospital, Tours

Samarbejdspartnere

Aerogen

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. juni 2026

Primær færdiggørelse (Anslået)

1. juli 2029

Studieafslutning (Anslået)

1. september 2029

Datoer for studieregistrering

Først indsendt

5. juni 2026

Først indsendt, der opfyldte QC-kriterier

18. juni 2026

Først opslået (Faktiske)

24. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

24. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • DR230005
  • 2023-510075-63-00 (Ctis)

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