The Variable Ventilation Trial (Part A)

NCT07791225 | Not Yet Recruiting DMC FDA Device

• 2 other identifiers: 2026P001935HT94252510768
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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:

• 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.

Conditions

ARDS (Acute Respiratory Distress Syndrome)

Outcome Measures

Primary Outcomes (9)

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  Barotrauma

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  Worsening Hypoxemia

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  Worsening ventilation

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  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

  Hemodynamic instability

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  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

  Self-extubation

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  Stroke

  Maximum of 24 hours of VV

• Safety assessed by the incidence of pre-specified AEs over the first 24 hours

  Death

  Maximum of 24 hours of VV

Secondary Outcomes (3)

• Lung mechanics

  Every 12 hours to maximum of 24 hours of VV

• Gas exchange

  Every 12 hours to maximum of 24 hours of VV

• Feasibility of VV implementation.

  Every 12 hours during 24 hours of VV

Study Arms (2)

Variable Ventilation

EXPERIMENTAL

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

Conventional Ventilation

PLACEBO COMPARATOR

Standard strategy of mechanical ventilation based on constant size low tidal volume implemented on a commercially available ventilator.

Device: Conventional Ventilation

Interventions

Variable Ventilation DEVICE

Strategy of mechanical ventilation based on varying tidal volume breath to breath to provide therapeutic benefits in patients with ARDS.

Variable Ventilation

Conventional Ventilation DEVICE

Strategy of mechanical ventilation based on delivery of a constant size low tidal volume.

Conventional Ventilation

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Baystate Medical Center: collaborator
• Boston University: collaborator
• Oregon Health and Science University: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Baystate Health

Springfield, Massachusetts, 01199, United States

Location

Montefiore Einstein

The Bronx, New York, 10461, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Intermountain Health Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Related Publications (14)

• 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.

  PMID: 21567115 BACKGROUND

• 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.

  PMID: 27511461 BACKGROUND

• 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.

  PMID: 22805999 BACKGROUND

• 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.

  PMID: 26213900 BACKGROUND

• 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.

  PMID: 19136581 BACKGROUND

• 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.

  PMID: 37387612 BACKGROUND

• 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.

  PMID: 16424726 BACKGROUND

• 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.

  PMID: 12851212 BACKGROUND

• 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.

  PMID: 18339891 BACKGROUND

• 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.

  PMID: 28690548 BACKGROUND

• 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.

  PMID: 23326543 BACKGROUND

• 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.

  PMID: 9603516 BACKGROUND

• 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.

  PMID: 11818322 BACKGROUND

• 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.

  PMID: 25803710 BACKGROUND

MeSH Terms

Conditions

Acute Lung Injury

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Rebecca Baron, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Baron, MD

CONTACT

617-525-6642; rbaron@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking will be used in this study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: August 27, 2026
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): August 31, 2031
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)