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Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia (TOP-MDRVAP)

2026年9月23日 更新者：Second Affiliated Hospital, Zhejiang University, School of Medicine

Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia: A Prospective, Multicenter, Double-Blind, Randomized Controlled Trial

The TOP-MDRVAP trial will test whether inhaled tobramycin can safely prevent pneumonia caused by multidrug-resistant bacteria in adults who need a breathing machine. Tobramycin is an antibiotic. Multidrug-resistant bacteria are bacteria that resist treatment with several types of antibiotics. Pneumonia that develops in patients receiving breathing support through a breathing tube is called ventilator-associated pneumonia (VAP). This study will evaluate tobramycin as a preventive treatment, rather than as treatment for existing VAP.

The study plans to enroll 574 adults aged 18 years or older in intensive care units (ICUs) at several hospitals. Participants must have received breathing support through a tube for 72 to 96 hours and be expected to need this support for at least another 72 hours. They must have at least one risk factor for infection with multidrug-resistant bacteria and must not have suspected or confirmed VAP when entering the study.

Participants will be assigned by chance to one of two groups, with an equal chance of entering either group. One group will receive tobramycin inhalation solution, 300 mg in 5 mL, twice daily for 3 consecutive days. The other group will receive 5 mL of 0.9% saline, a saltwater solution containing no antibiotic, on the same schedule. A nebulizer will turn the solution into a fine mist delivered through the breathing tube.

Both groups will receive standard measures to prevent VAP. Participants, their representatives, the healthcare professionals providing their direct care, and the researchers assessing outcomes will not know which study treatment each participant receives.

The main question is whether fewer participants develop VAP caused by multidrug-resistant bacteria within 28 days after assignment to a study group. Researchers will also compare the occurrence of VAP from any cause, antibiotic use, time receiving breathing support, time spent in the ICU and hospital, and deaths within 28 and 90 days.

Participants will be monitored for possible side effects, including kidney problems, narrowing of the airways, and complications involving the breathing tube or equipment. Samples will be tested for bacteria and antibiotic resistance. Follow-up will continue for up to 90 days after assignment, using hospital records or telephone contact to assess survival and recovery milestones, including discharge and the end of breathing support.

研究概览

地位

地位

指示当前招聘状态或扩展访问状态。
尚未招聘

条件

条件

正在研究的疾病、紊乱、综合征、疾病或损伤。在 ClinicalTrials.gov 上，条件还可能包括其他与健康相关的问题，例如寿命、生活质量和健康风险。

干预/治疗

干预/治疗

作为临床研究重点的过程或行动。干预措施包括药物、医疗设备、程序、疫苗和其他处于研究阶段或已经可用的产品。干预措施还可以包括非侵入性方法，例如教育或调整饮食和锻炼。

研究类型

研究类型

描述临床研究的性质。研究类型包括介入性研究（也称为临床试验）、观察性研究（包括患者登记）和扩展访问。
介入性

注册 (估计的)

注册

临床研究的参与者人数。 “预期”入组人数是研究人员进行研究所需的目标参与者人数。
574

阶段

阶段

根据美国食品和药物管理局 (FDA) 制定的定义，研究药物或生物制品的临床试验阶段。阶段基于研究的目标、参与者的数量和其他特征。有五个阶段：早期第 1 阶段（以前列为第 0 阶段）、第 1 阶段、第 2 阶段、第 3 阶段和第 4 阶段。不适用用于描述没有 FDA 定义的阶段的试验，包括设备试验或行为干预。
  • 第四阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习联系方式

可以回答临床研究注册问题的人员的姓名和联系信息。进行研究的每个地点也可能有特定的联系人，他们可能能够更好地回答这些问题。

研究联系人备份

学习地点

  • 中国
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310000
        • Second Affiliated Hospital of Zhejiang University School of Medicine
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

资格标准

想要参加临床研究的人必须满足的关键要求或他们必须具备的特征。资格标准包括纳入标准（一个人参与研究所必需的）和排除标准（阻止一个人参与）。资格标准的类型包括一项研究是否接受健康志愿者、是否有年龄或年龄组要求，或是否受性别限制。

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Age ≥18 years at enrollment.

  2. Invasive mechanical ventilation through an endotracheal tube for ≥72 hours and ≤96 hours, measured from the time of intubation, with an anticipated requirement for at least another 72 hours of invasive mechanical ventilation, as assessed by the attending physician.

  3. At least one of the following risk factors for multidrug-resistant (MDR) bacterial infection:

    3.1 Exposure to systemic antibiotics for ≥24 hours within the 30 days before enrollment.

    3.2 Current hospitalization for at least 120 hours before randomization. 3.3 Septic shock requiring vasoactive medication to maintain a mean arterial pressure ≥65 mmHg, with a blood lactate level >2 mmol/L.

    3.4 Moderate-to-severe acute respiratory distress syndrome (ARDS), according to the Berlin definition, with a PaO2/FiO2 ratio ≤200 mmHg and positive end-expiratory pressure (PEEP) ≥5 cm H2O.

    3.5 Current renal replacement therapy, including continuous renal replacement therapy or intermittent hemodialysis.

    3.6 A history of MDR bacterial colonization or infection within the previous 12 months, documented by clinical culture.

  4. Written informed consent obtained from the patient or the patient's legally authorized representative.

Exclusion Criteria:

  1. Suspected or confirmed ventilator-associated pneumonia (VAP) on the day of enrollment, based on the attending physician's clinical judgment.
  2. Continuous invasive mechanical ventilation for more than 96 hours before enrollment.
  3. Planned extubation within the next 24 hours.
  4. Previous tracheostomy.
  5. A history of allergy to tobramycin or any other aminoglycoside antibiotic.
  6. Use of tobramycin within the 7 days before enrollment; ongoing treatment with any aminoglycoside antibiotic at enrollment; or a clinical indication for intravenous treatment with any aminoglycoside antibiotic at enrollment.
  7. Chronic kidney disease (stages 4-5) with a baseline estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m², or acute kidney injury meeting the protocol-specified Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 criteria: serum creatinine increased to three times baseline, serum creatinine >353.6 μmol/L, urine output <0.3 mL/kg/hour for more than 24 hours, or anuria for more than 12 hours. Patients currently receiving renal replacement therapy are exempt from this renal exclusion criterion.
  8. Expected survival of no more than 48 hours, as assessed by the attending physician.
  9. Pregnancy, indicated by a positive serum or urine human chorionic gonadotropin (hCG) test, or breastfeeding.
  10. Concurrent participation in another interventional clinical study involving nebulized antibiotics or other ventilator-associated pneumonia prevention interventions.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：预防
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂

参与者组/臂

根据试验方案，接受特定干预/治疗或不接受干预的临床试验参与者组或亚组。
干预/治疗

干预/治疗

作为临床研究重点的过程或行动。干预措施包括药物、医疗设备、程序、疫苗和其他处于研究阶段或已经可用的产品。干预措施还可以包括非侵入性方法，例如教育或调整饮食和锻炼。
实验性的：Nebulized Tobramycin

Participants receive tobramycin inhalation solution, 300 mg in 5 mL per dose, administered through the endotracheal tube using a vibrating mesh nebulizer twice daily for 3 consecutive days (6 planned doses). The intervention is administered to prevent multidrug-resistant ventilator-associated pneumonia (MDR-VAP). Participants also receive standard ventilator-associated pneumonia (VAP) prevention measures.
药品：Tobramycin inhalation solution

Tobramycin inhalation solution (300 mg/5 mL) is administered at a dose of 300 mg (5 mL) twice daily for 3 consecutive days, for a total of 6 planned doses. The ready-to-use solution is administered without additional dilution through the endotracheal tube using a vibrating mesh nebulizer connected to the ventilator circuit. Each nebulization continues until the nebulizer reservoir is empty. The intervention is administered to prevent multidrug-resistant ventilator-associated pneumonia (MDR-VAP), in addition to standard VAP prevention measures.
安慰剂比较：Nebulized 0.9% Sodium Chloride Placebo

Participants receive 5 mL of 0.9% sodium chloride solution (normal saline) as a placebo, administered through the endotracheal tube using a vibrating mesh nebulizer twice daily for 3 consecutive days (6 planned doses). Participants also receive standard ventilator-associated pneumonia (VAP) prevention measures.
药品：0.9% Sodium Chloride Placebo

A 5 mL dose of 0.9% sodium chloride solution (normal saline) is administered as a placebo twice daily for 3 consecutive days, for a total of 6 planned doses. The solution is delivered through the endotracheal tube using the same type of vibrating mesh nebulizer, administration schedule, and nebulization procedure as the tobramycin intervention. Each nebulization continues until the nebulizer reservoir is empty. Participants also receive standard VAP prevention measures.

研究衡量的是什么？

主要结果指标

主要结果指标

在临床研究的方案中，对于评估干预/治疗的效果最重要的计划结果测量。大多数临床研究有一项主要结果指标，但有些研究有不止一项。
结果测量
措施说明
大体时间
28-Day Cumulative Incidence of Multidrug-Resistant Ventilator-Associated Pneumonia
大体时间：From randomization through Day 28.

Percentage of randomized participants with a first episode of multidrug-resistant ventilator-associated pneumonia (MDR-VAP), adjudicated by an independent blinded endpoint adjudication committee. VAP develops after 48 hours of mechanical ventilation, including within 48 hours after weaning or extubation. Diagnosis requires new or progressive infiltrates, consolidation, or ground-glass opacities on chest X-ray or CT plus at least two of: temperature >38°C, purulent airway secretions, and white blood cell count >10 x 10^9/L or <4 x 10^9/L. MDR-VAP additionally requires a positive quantitative lower respiratory tract culture (tracheal aspirate ≥10^5 CFU/mL; bronchoalveolar lavage ≥10^4 CFU/mL; protected specimen brush ≥10^3 CFU/mL) with a causative bacterium resistant to at least three antimicrobial classes.
From randomization through Day 28.

次要结果测量

次要结果测量

在临床研究的方案中，计划的结果测量值在评估干预效果时不如主要结果测量值重要，但仍然值得关注。大多数临床研究有不止一项次要结果指标。
结果测量
措施说明
大体时间
Incidence Density of Multidrug-Resistant Ventilator-Associated Pneumonia
大体时间：From randomization through Day 28.

Number of first episodes of multidrug-resistant ventilator-associated pneumonia per 1,000 invasive mechanical ventilation days accumulated during the assessment period.
From randomization through Day 28.
28-Day Incidence of Ventilator-Associated Pneumonia From Any Cause
大体时间：From randomization through Day 28.

28-Day Incidence of Ventilator-Associated Pneumonia From Any Cause
From randomization through Day 28.
Systemic Antibiotic Use Expressed as Antibiotic-Days
大体时间：From randomization through Day 28.

Cumulative systemic antibiotic use during the assessment period, expressed as antibiotic-days.
From randomization through Day 28.
Days of Exposure to Systemic Antibiotics
大体时间：From randomization through Day 28.

Number of days on which a participant receives at least one systemic antibiotic during the assessment period. Each day with systemic antibiotic exposure is counted once, regardless of the number of antibiotics administered.
From randomization through Day 28.
Duration of Mechanical Ventilation
大体时间：From randomization through Day 28.

Total duration of invasive and noninvasive mechanical ventilation, measured in days, during the assessment period.
From randomization through Day 28.
Intensive Care Unit Length of Stay
大体时间：From randomization to ICU discharge, assessed up to Day 90.

Duration of intensive care unit stay, measured in days from randomization to ICU discharge, with follow-up through Day 90.
From randomization to ICU discharge, assessed up to Day 90.
Hospital Length of Stay
大体时间：From randomization to hospital discharge, assessed up to Day 90.

Duration of hospital stay, measured in days from randomization to hospital discharge, with follow-up through Day 90.
From randomization to hospital discharge, assessed up to Day 90.
28-Day All-Cause Mortality
大体时间：From randomization through Day 28.

Percentage of participants who die from any cause within 28 days after randomization.
From randomization through Day 28.
90-Day All-Cause Mortality
大体时间：From randomization through Day 90.

Percentage of participants who die from any cause within 90 days after randomization. Survival status is obtained from hospital records or telephone follow-up.
From randomization through Day 90.
Incidence of Ventilator-Associated Pneumonia Caused by Tobramycin-Susceptible Gram-Negative Bacteria
大体时间：From randomization through Day 28.

Percentage of participants who develop ventilator-associated pneumonia caused by gram-negative bacteria that are susceptible to tobramycin on in vitro antimicrobial susceptibility testing.
From randomization through Day 28.
Incidence of Ventilator-Associated Events
大体时间：From randomization through Day 28.

Percentage of participants who develop a ventilator-associated event, assessed using the protocol-specified 2023 Centers for Disease Control and Prevention/National Healthcare Safety Network definitions. Assessments include ventilator-associated conditions, infection-related ventilator-associated complications, and possible ventilator-associated pneumonia.
From randomization through Day 28.
Incidence of New-Onset Acute Kidney Injury
大体时间：From randomization through Day 28.

Percentage of participants without acute kidney injury at baseline who develop Kidney Disease: Improving Global Outcomes (KDIGO) stage 1 or higher acute kidney injury during the assessment period.
From randomization through Day 28.
Daily Trajectory of the Clinical Pulmonary Infection Score
大体时间：Assessed daily from randomization until extubation or Day 28, whichever occurs first.

Daily Clinical Pulmonary Infection Score (CPIS) values and their longitudinal changes during the assessment period, calculated using available clinical data.
Assessed daily from randomization until extubation or Day 28, whichever occurs first.
Time to First Successful Spontaneous Breathing Trial
大体时间：From randomization through Day 28.

Time, measured in days, from randomization to the first successful spontaneous breathing trial (SBT) during the assessment period.
From randomization through Day 28.
Detection Rate of Tobramycin-Resistant Bacteria
大体时间：From randomization through Day 28.

Rate of isolation of tobramycin-resistant bacteria from respiratory specimens or blood cultures during the assessment period.
From randomization through Day 28.
Composite Incidence of Serious Nebulization-Related Adverse Effects
大体时间：From randomization through Day 28.

Percentage of participants experiencing at least one serious adverse effect related to nebulization, including increased expiratory filter resistance, bronchospasm, or endotracheal tube obstruction.
From randomization through Day 28.

其他结果措施

其他结果措施

对于临床试验，协议中描述的计划测量用于确定干预/治疗对参与者的影响。对于观察性研究，用于描述疾病或特征模式或与暴露、风险因素或治疗的关联的测量或观察。结果测量的类型包括主要结果测量和次要结果测量。
结果测量
措施说明
大体时间
Longitudinal Changes in Respiratory Microbiome Alpha Diversity
大体时间：Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.

Longitudinal changes in respiratory microbiome alpha diversity, assessed by 16S ribosomal RNA amplicon sequencing in participants enrolled in the microbiome substudy.
Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.
Longitudinal Changes in Respiratory Microbiome Beta Diversity
大体时间：Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.

Longitudinal changes in respiratory microbiome beta diversity, assessed by 16S ribosomal RNA amplicon sequencing in participants enrolled in the microbiome substudy.
Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.
Longitudinal Changes in Antibiotic Resistance Gene Abundance
大体时间：Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.

Longitudinal changes in antibiotic resistance gene abundance in respiratory samples, assessed by metagenomic next-generation sequencing.
Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.
Longitudinal Changes in Antibiotic Resistance Gene Diversity
大体时间：Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.

Longitudinal changes in antibiotic resistance gene diversity in respiratory samples, assessed by metagenomic next-generation sequencing.
Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.
Tobramycin Concentration-Time Profile in Epithelial Lining Fluid
大体时间：During the 3-day study treatment period.

Tobramycin concentrations in epithelial lining fluid over time in participants enrolled in the pharmacokinetic substudy.
During the 3-day study treatment period.
Plasma Tobramycin Concentration-Time Profile
大体时间：During the 3-day study treatment period.

Plasma tobramycin concentrations over time in participants enrolled in the pharmacokinetic substudy.
During the 3-day study treatment period.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

赞助

发起研究并有权和控制研究的组织或个人。
Second Affiliated Hospital, Zhejiang University, School of Medicine

合作者

合作者

为临床研究提供支持的赞助商以外的组织。这种支持可能包括与资金、设计、实施、数据分析或报告相关的活动。
RenJi Hospital
West China Hospital
Qilu Hospital of Shandong University
Ningbo Medical Center Lihuili Hospital
First Affiliated Hospital of Zhejiang University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jinhua People's Hospital
Second Affiliated Hospital of Wenzhou Medical University
Sir Run Run Shaw Hospital
Zhejiang Provincial People's Hospital
The First People's Hospital of Huzhou
Jinhua Central Hospital
Shanghai Tongji Hospital, Tongji University School of Medicine
Second Affiliated Hospital of Nanchang University
Taizhou Hospital
People's Hospital of Quzhou
Weifang People's Hospital
Lishui Country People's Hospital
The Fourth Affiliated Hospital of Zhejiang University School of Medicine
Zhengzhou Central Hospital
Zhejiang Hospital
Huang Shan People's Hospital
the second people's of kaifeng

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

学习开始

第一位参与者参加临床研究的实际日期。 “预期”研究开始日期是研究人员认为将成为研究开始日期的日期。
2026年10月7日

初级完成 (估计的)

初级完成

临床研究的最后一名参与者接受检查或接受干预以收集主要结果测量的最终数据的日期。临床研究是否根据方案结束或被终止不影响该日期。对于具有多个不同完成日期的主要结果测量的临床研究，该术语是指完成所有主要结果测量的数据收集的日期。 “预期”主要完成日期是研究人员认为将成为研究主要完成日期的日期。
2028年10月31日

研究完成 (估计的)

研究完成

临床研究中最后一位参与者接受检查或接受干预/治疗以收集主要结局指标、次要结局指标和不良事件（即最后一位参与者的最后一次就诊）的最终数据的日期。 “预期”研究完成日期是研究人员认为将成为研究完成日期的日期。
2029年1月29日

研究注册日期

首次提交

首次提交

研究发起人或研究者首次向 ClinicalTrials.gov 提交研究记录的日期。在首次提交日期和记录在 ClinicalTrials.gov 上的可用性（首次发布日期）之间通常会有几天的延迟。
2026年9月23日

首先提交符合 QC 标准的

首先提交符合 QC 标准的

研究发起人或研究者首次提交符合国家医学图书馆 (NLM) 质量控制 (QC) 审查标准的研究记录的日期。在满足 NLM 的 QC 审查标准之前，发起人或研究者可能需要修改和提交研究记录一次或多次。申办者或研究者有责任确保研究记录符合 NLM QC 审查标准。
2026年9月23日

首次发布 (实际的)

首次发布

在国家医学图书馆 (NLM) 质量控制 (QC) 审查结束后，研究记录首次在 ClinicalTrials.gov 上可用的日期。研究发起人或研究者提交研究记录的日期与首次发布日期之间通常会有几天的延迟。
2026年10月2日

研究记录更新

最后更新发布 (实际的)

最后更新发布

在 ClinicalTrials.gov 上提供研究记录更改的最近日期。研究发起人或研究者向 ClinicalTrials.gov 提交变更的时间（最后更新提交日期）和最后更新发布日期之间可能会有延迟。
2026年10月2日

上次提交的符合 QC 标准的更新

上次提交的符合 QC 标准的更新

研究发起人或研究者提交符合国家医学图书馆 (NLM) 质量控制 (QC) 审查标准的研究记录更改的最近日期。申办者或研究者有责任确保研究记录符合 NLM QC 审查标准。
2026年9月23日

最后验证

最后验证

研究发起人或研究者确认 ClinicalTrials.gov 上的临床研究信息准确且最新的最近日期。如果一项研究的招募状态为招募；尚未招聘；或活跃，未在过去 2 年内确认招募，该研究的招募状态显示为未知。
2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

其他研究编号

由研究的发起人、资助者或其他人分配给临床研究的标识符或 ID 号，而不是 NCT 号。这些编号可能包括来自其他试验登记处的唯一标识符和美国国立卫生研究院的资助编号。
  • 2026-0634

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

De-identified individual participant data underlying the results reported in the primary publication of the TOP-MDRVAP trial will be shared, together with a data dictionary. The dataset will include baseline characteristics, treatment allocation, and data supporting the reported efficacy and safety outcomes. Direct identifiers and the participant identification linkage file will not be shared. Data will be made available through controlled access for approved research proposals, subject to participant consent, institutional and ethics requirements, and applicable data-protection regulations.

IPD 共享时间框架

Data and supporting documents will be available beginning 6 months after publication of the primary trial results and ending 5 years after that publication.

IPD 共享访问标准

Access will be available to qualified researchers who submit a methodologically sound proposal for secondary analyses or individual participant data meta-analyses. Requests should be submitted to the principal investigator through the study contact listed in the trial registry. The principal investigator and the study Executive Committee will review the scientific merit, feasibility, and data-protection safeguards of each request. Approved applicants must sign a data use agreement limiting use to the approved research, prohibiting participant re-identification and unauthorized onward sharing, and requiring secure data storage. Data will be provided by secure electronic transfer after any required institutional, ethics, or regulatory approvals have been obtained.

IPD 共享支持信息类型

  • 研究方案
  • 树液

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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