The Variable Ventilation Trial (Part A) (VV (A))

August 25, 2026 updated by: 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:

  1. Is variable ventilation safe to use in adults with ARDS?
  2. 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
        • Contact:
    • Massachusetts
    • New York
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health & Science University
    • Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. Not more than 96 hours of mechanical ventilation before randomization
  3. Anticipated need for at least 48 more hours of controlled mechanical ventilation

  4. 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

  1. Age less than 21 years
  2. Pregnant or breastfeeding
  3. Prisoner
  4. Concurrent participation in another investigational drug study
  5. 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)
  6. No consent or inability to obtain consent or appropriate legal representative not available
  7. Physician refusal to allow enrollment in the trial
  8. Moribund patient not expected to survive 24 hours
  9. Treating team unwilling to use ARDS network low tidal volume strategy or variable ventilation mode
  10. Use, or planned use of ECMO
  11. Stroke (ischemic or hemorrhagic) or traumatic brain injury (TBI) within the prior 3 months
  12. Burns > 40% total body surface area (TBSA)
  13. Severe airway inhalational injury
  14. Diffuse alveolar hemorrhage

  15. Any of the following hallmarks of Severe COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 3 or 4

    1. FEV1 < 50% predicted
    2. Resting arterial blood gas values PaO2<55, SaO2<88%, or PaCO2>55
    3. Home invasive or non-invasive ventilation other than for sleep apnea
    4. Cor Pulmonale
    5. Candidate for, or has received, lung volume reduction surgery, bronchoscopic intervention to reduce end-expiratory lung volume, or lung transplantation

  16. Any of the following cardiac problems:

    1. Acute myocardial infarction (MI) or acute coronary syndrome within the last 90 days
    2. Coronary artery bypass graft (CABG) surgery within 30 days
    3. Angina pectoris, or use of nitrates, with activities of daily living
    4. Cardiopulmonary disease classified as NYHA class IV

    Physiological Exclusions

  17. Evidence of current barotrauma (e.g., pneumothorax, pneumomediastinum, or subcutaneous emphysema)
  18. Hemodynamic instability defined by inability to maintain a mean arterial pressure > 60 mm Hg.
  19. Other respiratory instability PEEP ≥18 cmH2O, suctioning more than hourly, Pplateau > 35 cm H2O, severe respiratory acidosis pH<7.25.
  20. Increased ICP > 20 cmH2O or mechanism of injury leading to concern for increased ICP
  21. Active bleeding with hemodynamic instability.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: Variable Ventilation
Strategy of mechanical ventilation based on varying tidal volume breath to breath to provide therapeutic benefits in patients with ARDS.
Placebo Comparator: Conventional Ventilation
Standard strategy of mechanical ventilation based on constant size low tidal volume implemented on a commercially available ventilator.
Device: Conventional Ventilation
Strategy of mechanical ventilation based on delivery of a constant size low tidal volume.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Barotrauma
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Worsening Hypoxemia
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Worsening ventilation
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
New onset arrhythmia requiring cardioversion
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Hemodynamic instability
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
ST-segment elevation myocardial infarction
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Self-extubation
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Stroke
Maximum of 24 hours of VV
Safety assessed by the incidence of pre-specified AEs over the first 24 hours
Time Frame: Maximum of 24 hours of VV
Death
Maximum of 24 hours of VV

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lung mechanics
Time Frame: Every 12 hours to maximum of 24 hours of VV
Lung compliance, airways resistance, peak and plateau pressures
Every 12 hours to maximum of 24 hours of VV
Gas exchange
Time Frame: Every 12 hours to maximum of 24 hours of VV
SpO2, PaO2/FiO2 ratio, oxygenation index, dead space, and lung injury score.
Every 12 hours to maximum of 24 hours of VV
Feasibility of VV implementation.
Time Frame: Every 12 hours during 24 hours of VV
Qualitative feedback from Research and Clinical staff of the device and implementation in the ICU setting.
Every 12 hours during 24 hours of VV

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Boston University
University of Alabama at Birmingham
Oregon Health and Science University
Baystate Medical Center

Investigators

  • Principal Investigator: Rebecca Baron, MD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2027

Primary Completion (Estimated)

February 1, 2031

Study Completion (Estimated)

August 31, 2031

Study Registration Dates

First Submitted

August 25, 2026

First Submitted That Met QC Criteria

August 25, 2026

First Posted (Actual)

August 27, 2026

Study Record Updates

Last Update Posted (Actual)

August 27, 2026

Last Update Submitted That Met QC Criteria

August 25, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026P001935
  • HT94252510768 (Other Grant/Funding Number: DOD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We will only be sharing data in agregate.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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