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

2026年6月18日 更新者：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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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).

研究の種類

介入

入学 (推定)

250

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Inhaled amikacin
薬：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).
薬：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).
プラセボコンパレーター：Inhaled NaCl 0.9%
薬：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).
薬：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).

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Incidence of transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia at day 28
時間枠：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

二次結果の測定

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University Hospital, Tours

協力者

Aerogen

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年6月1日

一次修了 (推定)

2029年7月1日

研究の完了 (推定)

2029年9月1日

試験登録日

最初に提出

2026年6月5日

QC基準を満たした最初の提出物

2026年6月18日

最初の投稿 (実際)

2026年6月24日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月24日

QC基準を満たした最後の更新が送信されました

2026年6月18日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

未定

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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