Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome
PREVENT VILI
PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial
3 other identifiers
interventional
1,100
1 country
24
Brief Summary
The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in patients with Acute Respiratory Distress Syndrome (ARDS). Participants will be ventilated according to one of two different strategies. The main question the study hopes to answer is whether the personalized ventilation strategy helps improve survival.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2024
Longer than P75 for phase_3
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 27, 2023
CompletedFirst Posted
Study publicly available on registry
October 4, 2023
CompletedStudy Start
First participant enrolled
June 24, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2030
June 25, 2025
June 1, 2025
5.3 years
September 27, 2023
June 20, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
60-day mortality
All-cause, all-location mortality
60 days from trial enrollment
Secondary Outcomes (4)
28-day mortality
28 days from trial enrollment
Alive and ventilator-free through 28 days
28 days from trial enrollment
Alive and Respiratory Support-Free
28 days from trial enrollment
Barotrauma through Day 14
14 days from trial enrollment
Other Outcomes (13)
Hemodynamic Instability Index through Hour 4 and daily through Day 7
From hour 4 through Day 7 from enrollment
Shock-free days through Day 28
28 days from trial enrollment
Duration of vasopressor support through Day 28
28 days from trial enrollment
- +10 more other outcomes
Study Arms (2)
Precision ventilation
EXPERIMENTALVentilator 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.
Guided usual care
ACTIVE COMPARATORVentilator 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.
Interventions
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.
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
You may qualify if:
- Age ≥ 18 years
- Moderate or severe ARDS, defined as meeting all of the following (a-e):
- Invasive ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O
- 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.
- Bilateral lung opacities on chest imaging not fully explained by effusions, lobar collapse, or nodules
- Respiratory failure not fully explained by heart failure or fluid overload
- Onset within 1 week of clinical insult or new/worsening symptoms
- 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
You may not qualify if:
- Esophageal manometry already in use clinically
- 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)
- 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
- Ongoing severe coagulopathy (platelet \< 5000/μL or INR \> 4)
- Extracorporeal membrane oxygenation (ECMO) or CO2 removal (ECCO2R)
- Neuromuscular disease that impairs spontaneous breathing (including but not limited to amyotrophic lateral sclerosis, Guillain-Barré syndrome, spinal cord injury at C5 or above)
- 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)
- Severe shock: norepinephrine-equivalent dose ≥ 0.6 μg/kg/min or simultaneous receipt of ≥ 3 vasopressors
- Severe liver disease, defined as Child-Pugh Class C (Section 12.3)
- ICU admission for burn injury
- Current ICU stay \> 2 weeks or acute care hospital stay \> 4 weeks
- Estimated mortality \> 50% over 6 months due to underlying chronic medical condition (e.g. metastatic pancreatic cancer) as assessed by the study physician
- 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
- 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.
- Treating clinician refusal or unwilling to use protocol-specified ventilator settings/modes
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Beth Israel Deaconess Medical Centerlead
- NYU Langone Healthcollaborator
- Massachusetts General Hospitalcollaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (24)
University of Arizona
Tucson, Arizona, 85724, United States
University of California, San Diego
La Jolla, California, 92093, United States
University of California, Los Angeles Medical Center
Los Angeles, California, 90024, United States
Cedar-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California, San Francisco
San Franciso, California, 94143, United States
University of Chicago
Chicago, Illinois, 60637, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
NYU Lagone Health
New York, New York, 02114, United States
New York City Health + Hospitals/ Bellevue
New York, New York, 10016, United States
Albert Einstein College of Medicine/Montefiore Medical Center
The Bronx, New York, 10461, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Baylor College of Medicine / St. Luke's Medical Center
Houston, Texas, 77030, United States
Intermountain Health
Murray, Utah, 84107, United States
University of Utah
Salt Lake City, Utah, 84132, United States
University of Washingont/Harborview Medical Center
Seattle, Washington, 98104, United States
Related Publications (2)
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.
PMID: 30776290BACKGROUNDNational 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.
PMID: 31112383BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel Talmor, MD MPH
Beth Israel Deaconess Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Masking Details
- Study team and leadership will be blinded to all analyses throughout the study. Unblinded statistician will perform analyses for the Data and Safety Monitoring Board (DSMB) and be sequestered from the remainder of the team.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor and Chair of Anaesthesia
Study Record Dates
First Submitted
September 27, 2023
First Posted
October 4, 2023
Study Start
June 24, 2024
Primary Completion (Estimated)
October 1, 2029
Study Completion (Estimated)
August 31, 2030
Last Updated
June 25, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Data will become available within one year of completion of the final follow up assessment, or within one year of primary manuscript publication, whichever comes first. Data will be available for 10 years.
- Access Criteria
- Outside investigators who wish to use data will submit a formal request, including rationale, analysis plan, and local Institutional Review Board (IRB) determination. The PREVENT VILI Executive Committee will review and respond to all requests. All data sharing will be codified by the appropriate contract / data use agreement. Recipient researchers must promise in writing to never attempt to access identifiable health/medical information or to attempt to identify the subject(s) who provided the specimen/data. Any intent to use materials or data for commercial purposes must be clearly disclosed as part of the request.
Data will be made publicly available via the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) repository. As per BioLINCC policy, data will be submitted within one year of completion of the final follow up assessment, or within one year of primary manuscript publication, whichever comes first.