The Variable Ventilation Trial (Part A) (VV (A))
2026年8月25日 更新者：Rebecca Baron、Brigham and Women's Hospital
A Bayesian, Operationally Seamless Adaptive Phase 2A/2B, Open-label, Multi-center, Randomized, Two-part Trial to Evaluate the Safety, Efficacy, and Optimal Tidal Volume Distribution of Variable Ventilation (VV) in Participants Undergoing Mechanical Ventilatory Support for Acute Respiratory Distress Syndrome
The goal of this clinical trial is to learn if a breathing machine (ventilator) method called "variable ventilation" can help protect the lungs of adult patients with acute respiratory distress syndrome (ARDS) who need help breathing through a ventilator. In variable ventilation, the size of each breath given by the machine changes slightly from breath to breath, instead of staying the same size in every breath. The study has two parts, A (safety and feasibility) and B (efficacy). This entry will cover the part A (safety study).
The main questions part A aims to answer are:
- Is variable ventilation safe to use in adults with ARDS?
- Is it feasible to deliver this method of ventilation to patients?
Researchers will compare variable ventilation to the standard breathing machine method used today to see if variable ventilation is safe and feasible.
Participants will be placed on an FDA approved ventilator that can deliver conventional mechanical ventilation and variable ventilation. Participants will:
- Have a period of stabilization on conventional ventilation, followed by 24 hours of variable ventilation, followed by 24 hours of conventional ventilation.
- Be checked regularly for breathing, oxygen levels, lung function, and plasma biomarkers.
研究概览
研究类型
介入性
注册 (估计的)
20
阶段
- 不适用
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
- 姓名：Rebecca Baron, MD
- 电话号码：617-525-6642
- 邮箱：rbaron@bwh.harvard.edu
学习地点
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Alabama
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Birmingham、Alabama、美国、35294
- University of Alabama at Birmingham
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接触：
- Peter Morris, MD
- 邮箱：pmorris@uabmc.edu
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Massachusetts
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Springfield、Massachusetts、美国、01199
- Baystate Health
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接触：
- Mark Tidswell, MD
- 邮箱：mark.tidswell@baystatehealth.org
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New York
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The Bronx、New York、美国、10461
- Montefiore Einstein
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接触：
- Luke Andrea
- 电话号码：314-705-0925
- 邮箱：landrea@montefiore.org
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接触：
- Daniel Ceusters
- 邮箱：dceuster@montefiore.org
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Oregon
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Portland、Oregon、美国、97239-3098
- Oregon Health & Science University
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Utah
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Murray、Utah、美国、84107
- Intermountain Health Intermountain Medical Center
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接触：
- Jessica Reimer
- 邮箱：Jessica.Reimer@imail.org
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接触：
- Emma Murphy
- 邮箱：Emma.Murphy@imail.org
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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
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- Patients ≥21 years old admitted to the Surgical, Trauma, Burn, Coronary or Medical ICUs with ARDS according to the Berlin criteria [50] and requiring mechanical ventilation will be eligible for inclusion.
- Not more than 96 hours of mechanical ventilation before randomization
- Anticipated need for at least 48 more hours of controlled mechanical ventilation
Intubated and mechanically ventilated for ARDS according to the Berlin criteria
- Hypoxemia of acute onset, within the past 7 days
- Mild or moderate hypoxemia, PaO2/FiO2 ratio 100 - 300 mm Hg
- Presence of a risk factor for ARDS
- Respiratory failure not fully explained by cardiac failure or fluid overload
- Bilateral opacities not explained by effusions, lobar collapse, or nodules
Exclusion Criteria:
Demographic
- Age less than 21 years
- Pregnant or breastfeeding
- Prisoner
- Concurrent participation in another investigational drug study
- Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if they would receive all supportive care except for attempts at resuscitation from cardiac arrest)
- No consent or inability to obtain consent or appropriate legal representative not available
- Physician refusal to allow enrollment in the trial
- Moribund patient not expected to survive 24 hours
- Treating team unwilling to use ARDS network low tidal volume strategy or variable ventilation mode
- Use, or planned use of ECMO
- Stroke (ischemic or hemorrhagic) or traumatic brain injury (TBI) within the prior 3 months
- Burns > 40% total body surface area (TBSA)
- Severe airway inhalational injury
- Diffuse alveolar hemorrhage
Any of the following hallmarks of Severe COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 3 or 4
- FEV1 < 50% predicted
- Resting arterial blood gas values PaO2<55, SaO2<88%, or PaCO2>55
- Home invasive or non-invasive ventilation other than for sleep apnea
- Cor Pulmonale
- Candidate for, or has received, lung volume reduction surgery, bronchoscopic intervention to reduce end-expiratory lung volume, or lung transplantation
Any of the following cardiac problems:
- Acute myocardial infarction (MI) or acute coronary syndrome within the last 90 days
- Coronary artery bypass graft (CABG) surgery within 30 days
- Angina pectoris, or use of nitrates, with activities of daily living
- Cardiopulmonary disease classified as NYHA class IV
Physiological Exclusions
- Evidence of current barotrauma (e.g., pneumothorax, pneumomediastinum, or subcutaneous emphysema)
- Hemodynamic instability defined by inability to maintain a mean arterial pressure > 60 mm Hg.
- Other respiratory instability PEEP ≥18 cmH2O, suctioning more than hourly, Pplateau > 35 cm H2O, severe respiratory acidosis pH<7.25.
- Increased ICP > 20 cmH2O or mechanism of injury leading to concern for increased ICP
- Active bleeding with hemodynamic instability.
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：治疗
- 分配：非随机化
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Variable Ventilation
Strategy of mechanical ventilation based on varying tidal volume breath to breath to provide therapeutic benefits in patients with ARDS.
The variable ventilation (VV) strategy will be implemented on a commercially available ventilator.
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Strategy of mechanical ventilation based on varying tidal volume breath to breath to provide therapeutic benefits in patients with ARDS.
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安慰剂比较：Conventional Ventilation
Standard strategy of mechanical ventilation based on constant size low tidal volume implemented on a commercially available ventilator.
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Strategy of mechanical ventilation based on delivery of a constant size low tidal volume.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Barotrauma
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Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Worsening Hypoxemia
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Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Worsening ventilation
|
Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
|
New onset arrhythmia requiring cardioversion
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Maximum of 24 hours of VV
|
|
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Hemodynamic instability
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Maximum of 24 hours of VV
|
|
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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ST-segment elevation myocardial infarction
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Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Self-extubation
|
Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Stroke
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Maximum of 24 hours of VV
|
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Safety assessed by the incidence of pre-specified AEs over the first 24 hours
大体时间：Maximum of 24 hours of VV
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Death
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Maximum of 24 hours of VV
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Lung mechanics
大体时间：Every 12 hours to maximum of 24 hours of VV
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Lung compliance, airways resistance, peak and plateau pressures
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Every 12 hours to maximum of 24 hours of VV
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Gas exchange
大体时间：Every 12 hours to maximum of 24 hours of VV
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SpO2, PaO2/FiO2 ratio, oxygenation index, dead space, and lung injury score.
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Every 12 hours to maximum of 24 hours of VV
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Feasibility of VV implementation.
大体时间：Every 12 hours during 24 hours of VV
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Qualitative feedback from Research and Clinical staff of the device and implementation in the ICU setting.
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Every 12 hours during 24 hours of VV
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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。
合作者
调查人员
- 首席研究员：Rebecca Baron, MD、Brigham and Women's Hospital
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Dellaca RL, Aliverti A, Lo Mauro A, Lutchen KR, Pedotti A, Suki B. Correlated variability in the breathing pattern and end-expiratory lung volumes in conscious humans. PLoS One. 2015 Mar 24;10(3):e0116317. doi: 10.1371/journal.pone.0116317. eCollection 2015.
- Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L370-5. doi: 10.1152/ajplung.00036.2003.
- Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002 Feb 1;165(3):366-71. doi: 10.1164/ajrccm.165.3.2010155.
- Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, Suki B. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006 Feb;34(2):439-45. doi: 10.1097/01.ccm.0000196208.01682.87.
- Berry CA, Suki B, Polglase GR, Pillow JJ. Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome. Pediatr Res. 2012 Oct;72(4):384-92. doi: 10.1038/pr.2012.97. Epub 2012 Jul 17.
- Bartolak-Suki E, Noble PB, Bou Jawde S, Pillow JJ, Suki B. Optimization of Variable Ventilation for Physiology, Immune Response and Surfactant Enhancement in Preterm Lambs. Front Physiol. 2017 Jun 23;8:425. doi: 10.3389/fphys.2017.00425. eCollection 2017.
- Arold SP, Bartolak-Suki E, Suki B. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture. Am J Physiol Lung Cell Mol Physiol. 2009 Apr;296(4):L574-81. doi: 10.1152/ajplung.90454.2008. Epub 2009 Jan 9.
- Suki B, Alencar AM, Sujeer MK, Lutchen KR, Collins JJ, Andrade JS Jr, Ingenito EP, Zapperi S, Stanley HE. Life-support system benefits from noise. Nature. 1998 May 14;393(6681):127-8. doi: 10.1038/30130. No abstract available.
- Pillow JJ, Musk GC, McLean CM, Polglase GR, Dalton RG, Jobe AH, Suki B. Variable ventilation improves ventilation and lung compliance in preterm lambs. Intensive Care Med. 2011 Aug;37(8):1352-9. doi: 10.1007/s00134-011-2237-x. Epub 2011 May 13.
- Suki B, Parameswaran H, Imsirovic J, Bartolak-Suki E. Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function. Physiology (Bethesda). 2016 Sep;31(5):346-58. doi: 10.1152/physiol.00051.2015.
- Bartolak-Suki E, Imsirovic J, Parameswaran H, Wellman TJ, Martinez N, Allen PG, Frey U, Suki B. Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function. Nat Mater. 2015 Oct;14(10):1049-57. doi: 10.1038/nmat4358. Epub 2015 Jul 27.
- Pillow JJ, Bartolak-Suki E, Noble PB, Berry CA, Suki B. Surfactant Protein Production during Maturation Is Enhanced by Natural Variability in Breathing. Am J Respir Cell Mol Biol. 2023 Jul;69(1):115-118. doi: 10.1165/rcmb.2022-0411LE. No abstract available.
- Thammanomai A, Hueser LE, Majumdar A, Bartolak-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1985). 2008 May;104(5):1329-40. doi: 10.1152/japplphysiol.01002.2007. Epub 2008 Mar 13.
- Thammanomai A, Hamakawa H, Bartolak-Suki E, Suki B. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury. PLoS One. 2013;8(1):e53934. doi: 10.1371/journal.pone.0053934. Epub 2013 Jan 9.
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)
2027年2月1日
初级完成 (估计的)
2031年2月1日
研究完成 (估计的)
2031年8月31日
研究注册日期
首次提交
2026年8月25日
首先提交符合 QC 标准的
2026年8月25日
首次发布 (实际的)
2026年8月27日
研究记录更新
最后更新发布 (实际的)
2026年8月27日
上次提交的符合 QC 标准的更新
2026年8月25日
最后验证
2026年8月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.