PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Acute Respiratory Distress Syndrome
- Sponsor
- Beth Israel Deaconess Medical Center
- Enrollment
- 1100
- Locations
- 24
- Primary Endpoint
- 60-day mortality
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
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.
Investigators
Daniel Talmor
Professor and Chair of Anaesthesia
Beth Israel Deaconess Medical Center
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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)
Outcomes
Primary Outcomes
60-day mortality
Time Frame: 60 days from trial enrollment
All-cause, all-location mortality
Secondary Outcomes
- 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)
- 28-day mortality(28 days from trial enrollment)