Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome

Phase 3

Recruiting

• Conditions: Respiratory Failure; Acute Respiratory Distress Syndrome

• Registration Number: NCT06066502
• Lead Sponsor: Beth Israel Deaconess Medical Center

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.

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 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.

Study Timeline

• Study First Submitted: 2023-09-27
• Study First Submitted QC: 2023-09-27
• Study First Posted: 2023-10-04
• Study Start: 2024-06-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-20
• Last Update Posted: 2025-06-25
• Primary Completion: 2029-10-01
• Study Completion: 2030-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

1. Age ≥ 18 years

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

1. Esophageal manometry already in use clinically
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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
60-day mortality	60 days from trial enrollment	All-cause, all-location mortality

Secondary Outcome Measures

Name	Time	Method
Alive and ventilator-free through 28 days	28 days from trial enrollment	A composite outcome that incorporates survival for the defined follow-up interval and time to successful liberation from invasive mechanical ventilation (IMV) among survivors.
Alive and Respiratory Support-Free	28 days from trial enrollment	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.
Barotrauma through Day 14	14 days from trial enrollment	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.
28-day mortality	28 days from trial enrollment	All-cause, all-location mortality

Trial Locations

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

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