Acute Respiratory Distress SyndromePhase 3PREVENT VILINCT06066502
Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome
A Phase 3 study testing Precision ventilation in people with Acute Respiratory Distress Syndrome and Respiratory Failure, run by Beth Israel Deaconess Medical Center at 33 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Respiratory Failure
- What is being tested?
- Precision ventilation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,100 participants
- Where
- 33 sitesUnited States
- Study dates
- 24 Jun 2024to 31 Dec 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Ventilator-dependent ARDS, with all of the following (a-e):
- Invasive ventilation with positive end-expiratory pressure (PEEP) ≥ 8 cm H2O or FiO2 ≥ 0.5
- Hypoxemia as characterized by: • If arterial blood gas (ABG) available: the partial pressure of oxygen in the arterial blood (PaO2)/FiO2 ≤ 300 mm Hg, or, • if ABG not available OR overt clinical deterioration in oxygenation since last ABG: SpO2/FiO2 ≤ 316 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.
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- 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 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
Who cannot join
- 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)
- Gross barotrauma or chest tube inserted to treat barotrauma (note: chest tube inserted strictly for drainage of pleural effusion is not an exclusion)
- Esophageal pathology that, in judgement of the site investigator, significantly increases risk of esophageal catheter placement, including high-risk esophageal varices, 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)
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- 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: cystic fibrosis, acute bronchiectasis exacerbation, acute exacerbation of a chronic interstitial lung disease (ILD), chronic pulmonary hypertension (PH) on PH-targeted vasoactive medication, or lung transplant
- End-stage chronic cirrhosis with Child-Pugh Class C (Section 12.3)
- ICU admission for burn injury
- Current ICU stay > 2 weeks or acute care hospital stay > 4 weeks
- 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
- Prisoner
- Previous enrollment in this trial
Trial locations and contacts
33 sites in 1 country. Contact the study team or a site near you to ask about taking part.
33 sites in 1 country
United States33 sites, 33 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Pauline K Park, MD, parkpk@med.umich.edu
Norman Olbrich, onorman@med.umich.edu
- Not yet recruiting
Emory University / Grady Health System
Atlanta, Georgia, 30322
Matthew R Thau, MD, matthew.ryan.thau@emory.edu
Vidhi Javia, vidhi.javia@emory.edu
- Recruiting
Tufts Medical Center
Boston, Massachusetts, 02111
Anthony Faugno, MD, Anthony.Faugno1@tuftsmedicine.org
Bipin Malla, Bipin.Malla@tuftsmedicine.org
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Lorenzo Berra, MD, lberra@mgh.harvard.edu
Cristina Mietto, MD, cmietto@mgh.harvard.edu
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Jakob Wollborn, MD, PhD, jwollborn@bwh.harvard.edu
Tayisha Examond, texamond@bwh.harvard.edu
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Valerie Goodspeed, MPH, 617-632-8055, vgoodspe@bidmc.harvard.edu
Daniel Talmor, MD MPH, 617-667-2902, dtalmor@bidmc.harvard.edu
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Danny Theodore, MD, dt7sj@uvahealth.org
Jennifer Phillips, jvp8a@uvahealth.org
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Bhakti Patel, MD, bpatel@bsd.uchicago.edu
Tasneem Tweel, tasneem.tweel@bsd.uchicago.edu
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
Kristin Hudock, MD, hudockkn@ucmail.uc.edu
Robert D Hite, MD, hitern@ucmail.uc.edu
- Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Eduardo Mireles-Cabodevila, MD, mirelee@ccf.org
- Recruiting
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Joshua A Englert, MD, Joshua.Englert@osumc.edu
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Christina Barkauskas, MD, christina.barkauskas@duke.edu
- Recruiting
Baylor College of Medicine / St. Luke's Medical Center
Houston, Texas, 77030
Christopher Howard, MD, christopher.howard@bcm.edu
cru_pulmonary@bcm.edu
- Recruiting
University of California, San Diego
La Jolla, California, 92093
Robert Owens, MD, rowens@health.ucsd.edu
Pamela N Deyoung, pdeyoung@health.ucsd.edu
- Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Harmeen Goraya, MD, HGoraya@uams.edu
Brandy Lee, BLee4@uams.edu
- Recruiting
University of California, Los Angeles Medical Center
Los Angeles, California, 90024
Steven Y Chang, MD, sychang@mednet.ucla.edu
Julia Vargas, JuliaVargas@mednet.ucla.edu
- Recruiting
Cedar-Sinai Medical Center
Los Angeles, California, 90048
Abirami Kumaresan, MD, Abirami.Kumaresan@cshs.org
Janice Emmanuella, DO, janice.emmanuella@cshs.org
- Not yet recruiting
Lowell General Hospital
Lowell, Massachusetts, 01854
Anthony Faugno, MD, anthony.faugno1@tuftsmedicine.org
Bipin Malla, bipin.malla@tuftsmedicine.org
- Recruiting
University of Miami
Miami, Florida, 33136
Alexander Fort, MD, acfort@med.miami.edu
Alessandro Colantuono Esaa, adc135@med.miami.edu
- Recruiting
Intermountain Health
Murray, Utah, 84107
Jennifer Edwards, MD, Jennifer.Edwards@imail.org
Sarah Duckworth, Sarah.Duckworth@imail.org
- Recruiting
NYU Lagone Health
New York, New York, 02114
Jeremy Beitler, MD MPH, Jeremy.Beitler@nyulangone.org
Alexis Serra, MD MPH, dl_aspire@nyulangone.org
- Recruiting
New York City Health + Hospitals/ Bellevue
New York, New York, 10016
Jeremy Beitler, MD, jeremy.beitler@nyulangone.org
dl_aspire@nyulangone.org
- Not yet recruiting
University of Oklahoma Health Sciences
Oklahoma City, Oklahoma, 73104
Huimin Wu, MD, Huimin-Wu@ou.edu
Blair Apple Hill, Blair-AppleHill@ouhsc.edu
- Recruiting
Stanford University
Palo Alto, California, 94305
Joseph Levitt, MD, jlevitt@stanford.edu
Rosemary Vojnik, rvojnik@stanford.edu
- Recruiting
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Michael Baram, MD, Michael.Baram@jefferson.edu
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
Akram Khan, MD, khana@ohsu.edu
Jose Pena, MD, penaj@ohsu.edu
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Gustavo Cortes Puentes, MD, CortesPuentes.Gustavo@mayo.edu
- Recruiting
University of Utah
Salt Lake City, Utah, 84132
Andrew Freeman, MD, Andrew.Freeman@hsc.utah.ed
Lindsey Waddoups, MS, lindsey.Waddoups@hsc.utah.edu
- Recruiting
University of California, San Francisco
San Franciso, California, 94143
Michael Matthay, MD, Michael.Matthay@ucsf.edu
Hanjing Zhou, MPH, hanjing.zhuo@ucsf.edu
- Recruiting
University of Washingont/Harborview Medical Center
Seattle, Washington, 98104
Nicholas J Johnson, MD, nickj45@uw.edu
Frances Nagore, francesn@uw.edu
- Recruiting
Albert Einstein College of Medicine/Montefiore Medical Center
The Bronx, New York, 10461
Ari L Moskowitz, MD MPH, amoskowitz@montefiore.org
- Recruiting
University of Arizona
Tucson, Arizona, 85724
Jarrod M Mosier, MD, jmosier@arizona.edu
Beth S Campbell, PhD, bsalvag@arizona.edu
- Recruiting
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
Kevin Gibbs, MD, kevin.gibbs@wfusm.edu
Darija Ward, MBA, darija.runjaicward@advocatehealth.org
About this study
Official title: PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial
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.
Read the detailed description
ARDS is a devastating condition that places a heavy burden on public health resources. Recent changes in the practice of mechanical ventilation have improved survival in ARDS, but mortality remains unacceptably high.
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 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 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 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 ARDS.
- Hypothesis 3: The precision ventilation strategy will decrease hemodynamic instability, measured as shock-free days through Day 14.
- Being tested
- Precision ventilation, Guided usual care ventilation
- Keywords
- critical care, critical illness, esophageal manometry, transpulmonary pressure, mechanical ventilation, lung stress
- Medical subject headings
- Respiratory Distress Syndrome, Respiratory Insufficiency, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Precision ventilationOther
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 ventilationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Precision ventilation | Experimental | 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. Receives: Other: Precision ventilation |
| Guided usual care | Active comparator | 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. Receives: Other: Guided usual care ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
60-day mortality
All-cause, all-location mortality
Measured: 60 days from randomization
Secondary outcomes (4)
28-day mortality
All-cause, all-location mortality
Measured: 28 days from randomization
Alive and ventilator-free through 28 days
A composite outcome that incorporates survival for the defined follow-up interval and time to successful liberation from invasive mechanical ventilation (IMV) among survivors.
Measured: 28 days from randomization
Alive and Respiratory Support-Free
A composite outcome that incorporates survival for the defined follow-up interval and time to successful liberation from advanced respiratory support among survivors. Advanced respiratory support is defined in Section 1.2. This outcome will be formulated as a win ratio and separately as a time-to-event competing risk endpoint.
Measured: 28 days from randomization
Barotrauma through Day 14
Any occurrence of pneumothorax, pneumomediastinum, subcutaneous emphysema, or chest tube insertion for barotrauma through Day 14 or until successful liberation from IMV, whichever occurs first.
Measured: 14 days from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2023
- Study start24 Jun 2024
- Primary completion1 Jul 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to the intervention arm or control arm. 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 1,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- NYU Langone Health, Massachusetts General Hospital, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Daniel Talmor, Beth Israel Deaconess Medical Center
- Investigators
- Daniel Talmor, MD MPH, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06066502
- Sponsor's protocol ID
- 2023P000682
- Other IDs
- 1U24HL166784, 1UG3HL166785
- Acronym
- PREVENT VILI
- Status last verified
- Jun 2026
- First submitted
- 27 Sep 2023
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 30776290National 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.
PubMed 31112383