Brief Summary
This phase II multi-centered, randomized controlled trial of mechanical ventilation directed by esophageal pressure measurement will test the primary hypothesis that using a strategy of maintaining a minimal but positive transpulmonary pressure (Ptp = airway pressure minus pleural pressure) throughout the ventilatory cycle will lead to an improvement in patient survival.
Brief Title
EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures
Detailed Description
This phase II prospective randomized controlled trial of ventilation directed by esophageal pressure measurements will enroll 200 patients with moderate to severe ARDS by the Berlin conference definition in several academic medical centers in North America. The control group will be ventilated using an alternative high-PEEP strategy with PEEP and FiO2 set using to an empiric table.
Plasma samples will be obtained at enrollment and days 3 and 7 and assessed for a variety of lung injury biomarkers to better assess the association between our intervention and the inflammation associated with mechanical ventilation and the development of ARDS. Hospital survivors will undergo a brief follow up phone survey to assess survival, functional status (Barthel Index), health-related QOL (Short Form 12), and frailty (VES) twelve months after enrollment.
The study length will be six years with a six month start-up period followed by a planned 50 month enrollment and twelve month follow-up.
Plasma samples will be obtained at enrollment and days 3 and 7 and assessed for a variety of lung injury biomarkers to better assess the association between our intervention and the inflammation associated with mechanical ventilation and the development of ARDS. Hospital survivors will undergo a brief follow up phone survey to assess survival, functional status (Barthel Index), health-related QOL (Short Form 12), and frailty (VES) twelve months after enrollment.
The study length will be six years with a six month start-up period followed by a planned 50 month enrollment and twelve month follow-up.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Respiratory Distress Syndrome
Eligibility Criteria
Inclusion Criteria:
* Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio \< 200 mmHg
2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
3. Respiratory failure not fully explained by cardiac failure or fluid overload
4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O
* Age 16 years or older
* Duration of ARDS 36 hours or less from meeting final Berlin criterion.
Exclusion Criteria:
* Received mechanical ventilation more than 96 hours
* Recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement
* Severe coagulopathy (platelet count \< 5000/microliter or INR \> 4)
* History of lung transplantation
* Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided
* Evidence of active air leak from the lung
* not committed to full support
* Participation in other intervention trials for ARDS or for sepsis within the past 30 days.
* Neuromuscular disease that impairs ability to ventilate spontaneously
* Severe chronic liver disease, defined as Child-Pugh Score of ≥12
* Treating clinician refusal, or unwillingness to commit to controlled ventilation for at least 24 hours
* Inability to get informed consent from the patient or surrogate.
* Use of rescue therapies for prior to enrollment (e.g. nitric oxide, ECMO, prone positioning, high frequency oscillation). This does not exclude cases where these therapies were used as the initial mode of ventilation
* Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio \< 200 mmHg
2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
3. Respiratory failure not fully explained by cardiac failure or fluid overload
4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O
* Age 16 years or older
* Duration of ARDS 36 hours or less from meeting final Berlin criterion.
Exclusion Criteria:
* Received mechanical ventilation more than 96 hours
* Recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement
* Severe coagulopathy (platelet count \< 5000/microliter or INR \> 4)
* History of lung transplantation
* Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided
* Evidence of active air leak from the lung
* not committed to full support
* Participation in other intervention trials for ARDS or for sepsis within the past 30 days.
* Neuromuscular disease that impairs ability to ventilate spontaneously
* Severe chronic liver disease, defined as Child-Pugh Score of ≥12
* Treating clinician refusal, or unwillingness to commit to controlled ventilation for at least 24 hours
* Inability to get informed consent from the patient or surrogate.
* Use of rescue therapies for prior to enrollment (e.g. nitric oxide, ECMO, prone positioning, high frequency oscillation). This does not exclude cases where these therapies were used as the initial mode of ventilation
Inclusion Criteria
Inclusion Criteria:
* Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio \< 200 mmHg
2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
3. Respiratory failure not fully explained by cardiac failure or fluid overload
4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O
* Age 16 years or older
* Duration of ARDS 36 hours or less from meeting final Berlin criterion.
* Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio \< 200 mmHg
2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
3. Respiratory failure not fully explained by cardiac failure or fluid overload
4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O
* Age 16 years or older
* Duration of ARDS 36 hours or less from meeting final Berlin criterion.
Gender
All
Gender Based
false
Keywords
ARDS
mechanical ventilation
ALI
esophageal pressure
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
16 Years
NCT Id
NCT01681225
Org Class
Other
Org Full Name
Beth Israel Deaconess Medical Center
Org Study Id
2009P000374
Overall Status
Completed
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)
Primary Outcomes
Outcome Description
The trial will utilize a primary composite endpoint that incorporates death and days off the ventilator at 28 days in such a manner that death constitutes a more serious outcome. Every subject is compared to every other subject in the trial and assigned one number resulting from each comparison. Since mortality outcome is clinically more important, mortality takes precedence over days off the ventilator. The sum of scores for patients in the treatment group is compared to the sum of scores of subjects in the control group to form a test statistic by the Mann-Whitney technique.
Outcome Measure
A composite outcome of mortality and time off the ventilator at 28-days.
Outcome Time Frame
Day 28
Secondary Ids
Secondary Id
UM1HL108724
Secondary Outcomes
Outcome Description
Number of calendar days breathing unassisted.
Outcome Time Frame
Day 28
Outcome Measure
Ventilator free days to day 28
Outcome Description
Hospital and ICU mortality to day 60
Outcome Time Frame
Day 60
Outcome Measure
mortality
Outcome Description
Hospital and ICU lengths of stay to days 28 and 60
Outcome Time Frame
Day 60
Outcome Measure
lengths of stay
Outcome Description
Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
Outcome Time Frame
Day 7
Outcome Measure
biomarkers of lung injury
Outcome Description
Mortality to 1 year
Outcome Time Frame
1 year
Outcome Measure
Survival
Outcome Description
Rescue measures will be chosen according to the practice at the clinical site, and may include repeated recruitment maneuvers, prone positioning, nitric oxide, epoprostenol sodium, airway pressure release ventilation, high frequency ventilation, or ECMO.
Outcome Time Frame
Day 28
Outcome Measure
Need for rescue therapy
Outcome Description
Will assess via questionnaire (Barthel Index) done by phone at 1 year. Barthel Index scores range from 0-100, with 100 representing greatest independence of activities of daily living.
Outcome Time Frame
1 year
Outcome Measure
Activities of daily living
Outcome Description
Will assess via questionnaire (12-Item Short-Form Health Survey \[SF-12\]) done by phone at 1 year. The SF-12 scores range from 0-100 points, with higher scores representing the highest level of health.
Outcome Time Frame
1 year
Outcome Measure
Self-reported health assessment
Outcome Description
Will assess via questionnaire (Vulnerable Elders-13 Survey) done by phone at 1 year. VES scores range from 0-10 points, with higher scores representing greater risk.
Outcome Time Frame
1 year
Outcome Measure
Frailty in patients age 65 and older
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
16
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michelle Gong
Investigator Email
mgong@montefiore.org
Investigator Phone
718-920-5464