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

18. Juni 2026 aktualisiert von: 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.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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).

Studientyp

Interventionell

Einschreibung (Geschätzt)

250

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Inhaled amikacin
Arzneimittel: 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).
Arzneimittel: 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%
Arzneimittel: 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).
Arzneimittel: 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).

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 28
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 7
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: From randomization to day 28
From randomization to day 28
Time to resolution of clinical signs of ventilator-associated tracheobronchitis
Zeitfenster: 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
Zeitfenster: Day 7
Day 7
Total duration of mechanical ventilation
Zeitfenster: From randomization to day 90
Number of days with mechanical ventilation
From randomization to day 90
Number of ventilator-free days at day 28
Zeitfenster: From randomization to day 28
From randomization to day 28
The number of days with systemic antibiotics at Day 28
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: From randomization to day 28
From randomization to day 28
Lenght of stay in the intensive care unit
Zeitfenster: From randomization to day 90
From randomization to day 90
Lenght of hospital stay
Zeitfenster: From randomization to day 90
From randomization to day 90
All-cause mortality at day 28
Zeitfenster: From randomization to day 28
From randomization to day 28
All-cause mortality at day 90
Zeitfenster: From randomization to day 90
From randomization to day 90
Health-related quality of life at day 90
Zeitfenster: 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
Zeitfenster: From randomization to day 28
Safety analysis
From randomization to day 28
Occurrence of respiratory adverse events related to amikacin nebulization
Zeitfenster: From randomization to day 90
Safety analysis
From randomization to day 90
Peak serum amikacin concentration 1 hour after inhaled study-drug nebulization
Zeitfenster: 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.
Zeitfenster: 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.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

University Hospital, Tours

Mitarbeiter

Aerogen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. Juni 2026

Primärer Abschluss (Geschätzt)

1. Juli 2029

Studienabschluss (Geschätzt)

1. September 2029

Studienanmeldedaten

Zuerst eingereicht

5. Juni 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

18. Juni 2026

Zuerst gepostet (Tatsächlich)

24. Juni 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

24. Juni 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

18. Juni 2026

Zuletzt verifiziert

1. Juni 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

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

Plan für individuelle Teilnehmerdaten (IPD)

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UNENTSCHIEDEN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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