Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome
NCT ID: NCT06066502
Last Updated: 2025-06-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
1100 participants
INTERVENTIONAL
2024-06-24
2030-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
PRotective VENTilation in Patients Without ARDS
NCT02153294
Strategies for Optimal Lung Ventilation in ECMO for ARDS: The SOLVE ARDS Study
NCT01990456
Implementation of Nudges to Promote Utilization of Low Tidal Volume Ventilation (INPUT) Study
NCT04663802
Strategy of UltraProtective Lung Ventilation With Extracorporeal CO2 Removal for New-Onset Moderate to seVere ARDS
NCT02282657
IMV to Accelerate Recovery of Lung Function in Veno-venous Extracorporeal Membrane Oxygenation; Lung Rest Or Moderate Mechanical Ventilation in ECMO
NCT06006676
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This application is for support of a phase III multi-centered, randomized controlled trial of mechanical ventilation, directed by driving pressure and esophageal manometry, in patients with moderate or severe ARDS. The primary hypothesis is that precise ventilator titration to maintain lung stress within 0-12 centimeters of water (cm H2O), the normal physiological range experienced during relaxed breathing, will improve 60-day mortality, compared to guided usual care.
Specific Aim 1: To determine the effect on mortality of the precision ventilation strategy, compared to guided usual care, in patients with moderate or severe ARDS.
• Hypothesis 1: The precision ventilation strategy will decrease 60-day mortality (primary trial endpoint).
Specific Aim 2: To evaluate the effects on lung injury of the precision ventilation strategy, compared to guided usual care, in patients with moderate or severe ARDS.
* Hypothesis 2a: The precision ventilation strategy will improve clinical pulmonary recovery, defined using the composite endpoint alive and ventilator-free (AVF).
* Hypothesis 2b: The precision ventilation strategy will attenuate alveolar epithelial injury.
Specific Aim 3: To evaluate the hemodynamic safety profile of the precision ventilation strategy, compared to guided usual care, in patients with moderate or severe ARDS.
• Hypothesis 3: The precision ventilation strategy will decrease hemodynamic instability, measured as shock-free days through Day 28.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
Participants in the intervention group (precision ventilation), will have mechanical ventilation using settings directed by the amount of air pressure in the chest and lungs, using esophageal manometry. The treating clinical team is not masked to esophageal and transpulmonary pressure values and can view these data throughout the period of protocol-directed ventilation.
Participants in the control group (guided usual care), will have ventilator support (low tidal volume mechanical ventilation) managed by the clinical team per usual care. The treating clinical team is masked to esophageal and transpulmonary pressure values and cannot view or be informed of these data at any time during the period of protocol-directed ventilation. An esophageal catheter will be inserted strictly for monitoring of respiratory mechanics by study staff, but values will not be used to titrate the ventilator.
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Precision ventilation
Ventilator support will be calibrated to maintain the range of lung stress typical of relaxed breathing in healthy adults. The ventilator management protocol takes into account pleural pressure, tidal volume and driving pressure, fraction of inspired oxygen (FiO2) and oxygen saturation (SpO2), and positive end-expiratory pressure (PEEP) titration.
Precision ventilation
The intervention arm prioritizes mitigation of ventilator-induced-lung-injury by individualizing support to patient-specific mechanics in an integrated approach to limit overdistension and atelectrauma. This is accomplished in this arm by titration of tidal volume to limitation of driving pressure at 12 centimeters of water (cmH2O) or less and using esophageal manometry to titrate PEEP to a transpulmonary pressure of 0 cmH2O with adjustments in respiratory rate to allow for permissive hypercapnia and FiO2 adjustments to assure adequate oxygenation.
Guided usual care
Ventilator support will be managed by the clinical team per usual care with select protocol-based guard rails to avoid practice extremes beyond the current body of evidence. PEEP titration will be performed by the clinical team within the limits set in. The allowable combinations of PEEP and FiO2 in the control arm reflect pre-intervention usual care observed at baseline in the recent large federally-funded multicenter ARDS trials.
Guided usual care ventilation
The comparison arm allows clinician discretion when titrating PEEP and tidal volume, while setting general targets for allowable PEEP/FiO2 combinations, target range for SpO2, and target range for tidal volume. This arm applies routine best-practice guidelines. This includes maintenance of tidal volumes of 6-8 cc/kg of ideal body weight, limiting plateau pressures to 30 cmH2O or less and application of PEEP-FiO2 combinations which include a wide range of typical usual care with esophageal manometry only for data collection and not clinical adjustment.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Precision ventilation
The intervention arm prioritizes mitigation of ventilator-induced-lung-injury by individualizing support to patient-specific mechanics in an integrated approach to limit overdistension and atelectrauma. This is accomplished in this arm by titration of tidal volume to limitation of driving pressure at 12 centimeters of water (cmH2O) or less and using esophageal manometry to titrate PEEP to a transpulmonary pressure of 0 cmH2O with adjustments in respiratory rate to allow for permissive hypercapnia and FiO2 adjustments to assure adequate oxygenation.
Guided usual care ventilation
The comparison arm allows clinician discretion when titrating PEEP and tidal volume, while setting general targets for allowable PEEP/FiO2 combinations, target range for SpO2, and target range for tidal volume. This arm applies routine best-practice guidelines. This includes maintenance of tidal volumes of 6-8 cc/kg of ideal body weight, limiting plateau pressures to 30 cmH2O or less and application of PEEP-FiO2 combinations which include a wide range of typical usual care with esophageal manometry only for data collection and not clinical adjustment.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Moderate or severe ARDS, defined as meeting all of the following (a-e):
1. Invasive ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O
2. Hypoxemia as characterized by: • If arterial blood gas (ABG) available: the partial pressure of oxygen in the arterial blood (PaO2)/FiO2 ≤ 200 mm Hg, or, • if ABG not available OR overt clinical deterioration in oxygenation since last ABG: SpO2/FiO2 ≤ 235 with SpO2 ≤ 97% (both conditions) on two representative assessments between 1 to 6 hours apart. • If patient is positioned prone or receiving inhaled pulmonary vasodilator at time of screening:
Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) that was recorded within the 6 hours immediately prior to initiating either of these therapies may be used for eligibility determination. • If PEEP has been increased by \> 5 cm H2O within the last 12 hours immediately prior to screening:
Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) prior to PEEP increase may be used for eligibility determination if recorded within this 12-hour window.
3. Bilateral lung opacities on chest imaging not fully explained by effusions, lobar collapse, or nodules
4. Respiratory failure not fully explained by heart failure or fluid overload
5. Onset within 1 week of clinical insult or new/worsening symptoms
3. Early in ARDS course
* Full criteria for moderate-severe ARDS (#2 above) first met within previous 3 days
* Current invasive ventilation episode not more than 4 days duration
* Current severe hypoxemic episode (receipt of invasive ventilation, noninvasive ventilation, or high-flow nasal cannula) not more than 10 days duration
Exclusion Criteria
2. Severe brain injury: including suspected elevated intracranial pressure, cerebral edema, or Glasgow coma score (GCS) ≤ 8 directly caused by severe brain injury (e.g., ischemia or hemorrhage)
3. Gross barotrauma or chest tube inserted to treat barotrauma (note: chest tube inserted strictly for drainage of pleural effusion is not an exclusion)
4. Esophageal varix or stricture that, in judgement of the site investigator, significantly increases risk of esophageal catheter placement; recent oropharyngeal or gastroesophageal surgery; or past esophagectomy
5. Ongoing severe coagulopathy (platelet \< 5000/μL or INR \> 4)
6. Extracorporeal membrane oxygenation (ECMO) or CO2 removal (ECCO2R)
7. Neuromuscular disease that impairs spontaneous breathing (including but not limited to amyotrophic lateral sclerosis, Guillain-Barré syndrome, spinal cord injury at C5 or above)
8. Any of the following severe chronic lung diseases: continuous home supplemental oxygen \> 3 liters/minute, pulmonary fibrosis, cystic fibrosis, lung transplant, or acute exacerbation of a chronic interstitial lung disease (ILD)
9. Severe shock: norepinephrine-equivalent dose ≥ 0.6 μg/kg/min or simultaneous receipt of ≥ 3 vasopressors
10. Severe liver disease, defined as Child-Pugh Class C (Section 12.3)
11. ICU admission for burn injury
12. Current ICU stay \> 2 weeks or acute care hospital stay \> 4 weeks
13. Estimated mortality \> 50% over 6 months due to underlying chronic medical condition (e.g. metastatic pancreatic cancer) as assessed by the study physician
14. Moribund patient not expected to survive 24 hours as assessed by the study physician; if cardiopulmonary resuscitation (CPR) was provided, assessment for moribund status must occur at least 6 hours after CPR was completed
15. Current limitation on life-sustaining care (other than do-not-resuscitate), or expectation by clinical team that a limitation on life-sustained care will be adopted within next 24 hours.
16. Treating clinician refusal or unwilling to use protocol-specified ventilator settings/modes
17. Prisoner
18. Previous enrollment in this trial
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
NYU Langone Health
OTHER
Massachusetts General Hospital
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Beth Israel Deaconess Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Daniel Talmor
Professor and Chair of Anaesthesia
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Daniel Talmor, MD MPH
Role: PRINCIPAL_INVESTIGATOR
Beth Israel Deaconess Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Arizona
Tucson, Arizona, United States
University of California, San Diego
La Jolla, California, United States
University of California, Los Angeles Medical Center
Los Angeles, California, United States
Cedar-Sinai Medical Center
Los Angeles, California, United States
University of California, San Francisco
San Franciso, California, United States
University of Chicago
Chicago, Illinois, United States
Tufts Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
NYU Lagone Health
New York, New York, United States
New York City Health + Hospitals/ Bellevue
New York, New York, United States
Albert Einstein College of Medicine/Montefiore Medical Center
The Bronx, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, United States
University of Cincinnati
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
Baylor College of Medicine / St. Luke's Medical Center
Houston, Texas, United States
Intermountain Health
Murray, Utah, United States
University of Utah
Salt Lake City, Utah, United States
University of Washingont/Harborview Medical Center
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Role: backup
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.