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

18 de junio de 2026 actualizado por: 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.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

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).

Tipo de estudio

Intervencionista

Inscripción (Estimado)

250

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Francia
      • Angers, Francia, 49933
        • 06 - ANGERS - Intensive care, University Hospital
        • Contacto:
        • Investigador principal:
          • Tchamba Achille KOUATCHET
      • Argenteuil, Francia
        • 04 - ARGENTEUIL - Intensive care, University Hospital
        • Investigador principal:
          • Gaëtan PLANTEFEVE
        • Contacto:
      • Blois, Francia
        • 11 - BLOIS, Intensive care, Hospital
        • Investigador principal:
          • Julien GROUILLE
        • Contacto:
          • Julien GROUILLE
          • Número de teléfono: 02 54 55 60 73
          • Correo electrónico: grouilj@ch-blois.fr
      • Bourg-en-Bresse, Francia, 01012
        • 09 - BOURG-EN-BRESSE, Intensive care, Hospital
        • Contacto:
        • Investigador principal:
          • Adrien ROBINE
      • Créteil, Francia, 94010
        • 10 - HENRI MONDOR, Intensive care, University Hospital
        • Contacto:
        • Investigador principal:
          • Pierre BAY
      • Dieppe, Francia, 76202
        • 07 - DIEPPE - Intensive care, University Hospital
        • Investigador principal:
          • Pierre-Louis DECLERCQ
        • Contacto:
      • Dijon, Francia, 21000
        • 08 - DIJON - Intensive care, University Hospital
        • Investigador principal:
          • Jean-Pierre QUENOT
        • Contacto:
      • Dreux, Francia, 28100
        • 12 - DREUX, Intensive care, Hospital
      • Le Chesnay, Francia, 78150
        • 14 - VERSAILLES, Intensive care, Hospital
        • Investigador principal:
          • Alexis FERRE
        • Contacto:
          • Alexis FERRE
          • Número de teléfono: 01 39 63 87 00
          • Correo electrónico: aferre@ght78sud.fr
      • Le Mans, Francia, 72037
        • 05 - LE MANS - Intensive care, University Hospital
        • Investigador principal:
          • Mickaël LANDAIS
        • Contacto:
      • Lyon, Francia, 69437
        • 15 - LYON EH, Intensive care, University Hospital
        • Investigador principal:
          • Laurent ARGAUD
        • Contacto:
      • Orléans, Francia, 45000
        • 01 - ORLEANS - Intensive care, University Hospital
        • Investigador principal:
          • François BARBIER
        • Contacto:
      • Paris, Francia, 32700
        • 17 - LOUIS MOURIER, Intensive care, University Hospital
        • Investigador principal:
          • Damien ROUX
        • Contacto:
      • Paris, Francia
        • 13 - BICHAT, Intensive care, Univerity Hospital
        • Investigador principal:
          • Jean-François TIMSIT
        • Contacto:
      • Pierre-Bénite, Francia, 69495
        • 16 - LYON SUD, Intensive care, University Hospital
        • Contacto:
        • Investigador principal:
          • Donatien DE MARIGNAN
      • Strasbourg, Francia, 67091
        • 03 - STRASBOURG - Intensive care, University Hospital
        • Investigador principal:
          • Julien DEMISELLE
        • Contacto:
      • Tours, Francia, 37044
        • 02 - TOURS - Intensive care, University Hospital
        • Investigador principal:
          • Stephan EHRMANN
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Inhaled amikacin
Droga: 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).
Droga: 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).
Comparador de placebos: Inhaled NaCl 0.9%
Droga: 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).
Droga: 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).

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 28
Periodo de tiempo: 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

Medidas de resultado secundarias

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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

University Hospital, Tours

Colaboradores

Aerogen

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de junio de 2026

Finalización primaria (Estimado)

1 de julio de 2029

Finalización del estudio (Estimado)

1 de septiembre de 2029

Fechas de registro del estudio

Enviado por primera vez

5 de junio de 2026

Primero enviado que cumplió con los criterios de control de calidad

18 de junio de 2026

Publicado por primera vez (Actual)

24 de junio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

24 de junio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

18 de junio de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

INDECISO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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