RecruitingPhase 3NCT06066502

Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome

PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial


Sponsor

Beth Israel Deaconess Medical Center

Enrollment

1,100 participants

Start Date

Jun 24, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria13

  • 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

Exclusion Criteria18

  • 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 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
  • Prisoner
  • Previous enrollment in this trial

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Interventions

OTHERPrecision 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.

OTHERGuided 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.


Locations(24)

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

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NCT06066502


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