Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

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

18 de junho de 2026 atualizado 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.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

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 estudo

Intervencional

Inscrição (Estimado)

250

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Inhaled amikacin
Medicamento: 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).
Medicamento: 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 Placebo: Inhaled NaCl 0.9%
Medicamento: 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).
Medicamento: 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).

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 28
Prazo: 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 resultados secundários

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

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

University Hospital, Tours

Colaboradores

Aerogen

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de junho de 2026

Conclusão Primária (Estimado)

1 de julho de 2029

Conclusão do estudo (Estimado)

1 de setembro de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

5 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

18 de junho de 2026

Primeira postagem (Real)

24 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

24 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

18 de junho de 2026

Última verificação

1 de junho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

INDECISO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever