Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome
Purpose
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.
Conditions
- Acute Respiratory Distress Syndrome
- Respiratory Failure
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention 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.
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
- Masking Description
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Active Comparator 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. |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Beth Israel Deaconess Medical Center
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.