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.
Brief Title
Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome
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.
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
6176328055
Central Contact Email
vgoodspe@bidmc.harvad.edu
Central Contact Role
Contact
Central Contact Phone
617-724-9836
Central Contact Email
nringwood@mgh.harvard.edu
Completion Date
Completion Date Type
Estimated
Conditions
Acute Respiratory Distress Syndrome
Respiratory Failure
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
critical care
critical illness
esophageal manometry
transpulmonary pressure
mechanical ventilation
lung stress
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06066502
Org Class
Other
Org Full Name
Beth Israel Deaconess Medical Center
Org Study Id
2023P000682
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
PREcision VENTilation to Attenuate Ventilator-Induced Lung Injury: A Phase 3 Multicenter Randomized Clinical Trial
Primary Outcomes
Outcome Description
All-cause, all-location mortality
Outcome Measure
60-day mortality
Outcome Time Frame
60 days from trial enrollment
Secondary Ids
Secondary Id
1U24HL166784
Secondary Id
1UG3HL166785
Secondary Outcomes
Outcome Description
All-cause, all-location mortality
Outcome Time Frame
28 days from trial enrollment
Outcome Measure
28-day mortality
Outcome Description
A composite outcome that incorporates survival for the defined follow-up interval and time to successful liberation from invasive mechanical ventilation (IMV) among survivors.
Outcome Time Frame
28 days from trial enrollment
Outcome Measure
Alive and ventilator-free through 28 days
Outcome Description
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.
Outcome Time Frame
28 days from trial enrollment
Outcome Measure
Alive and Respiratory Support-Free
Outcome Description
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.
Outcome Time Frame
14 days from trial enrollment
Outcome Measure
Barotrauma through Day 14
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ari Moskowitz
Investigator Email
amoskowitz@montefiore.org