EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures
- Conditions
- Acute Respiratory Distress Syndrome
- Interventions
- Other: Esophageal-pressure guided mechanical ventilationOther: High PEEP mechanical ventilation
- Registration Number
- NCT01681225
- Lead Sponsor
- Beth Israel Deaconess Medical Center
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
-
Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:
- Hypoxemic respiratory failure with PaO2 / FIO2 ratio < 200 mmHg
- b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days
- Respiratory failure not fully explained by cardiac failure or fluid overload
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EPVent Esophageal-pressure guided mechanical ventilation The overall goals for the "EPVent" group (esophageal-pressure guided mechanical ventilation) are to employ an open-lung strategy that includes low tidal volumes and maintenance of a positive transpulmonary pressure at end-expiration \[Ptpexp\]. Fraction of inspired oxygen \[FiO2\] and transpulmonary pressure pressure during an expiratory hold will be changed to achieve values shown in one of the columns of a protocol-specified table to meet the oxygenation target. Control High PEEP mechanical ventilation The overall goals for the Control group are similar to those for the EPVent group: to employ an open-lung strategy that includes low tidal volumes using an alternative high positive end-expiratory pressure \[PEEP\] strategy. The control group PEEP and tidal volume will be managed without reference to the esophageal pressure measurements, and instead will follow an empiric high PEEP mechanical ventilation strategy. PEEP and FiO2 will be raised or lowered to achieve the oxygenation target level specified in a study table.
- Primary Outcome Measures
Name Time Method A composite outcome of mortality and time off the ventilator at 28-days. Day 28 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.
- Secondary Outcome Measures
Name Time Method Ventilator free days to day 28 Day 28 Number of calendar days breathing unassisted.
mortality Day 60 Hospital and ICU mortality to day 60
biomarkers of lung injury Day 7 Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
Survival 1 year Mortality to 1 year
Activities of daily living 1 year 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.
Frailty in patients age 65 and older 1 year 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.
Self-reported health assessment 1 year 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.
Need for rescue therapy Day 28 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.
lengths of stay Day 60 Hospital and ICU lengths of stay to days 28 and 60
Trial Locations
- Locations (14)
University of California at San Diego
🇺🇸La Jolla, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Orlando Health
🇺🇸Orlando, Florida, United States
Shock-Trauma University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
St Joseph's Healthcare
🇨🇦Hamilton, Ontario, Canada
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Laval University
🇨🇦Quebec City, Quebec, Canada
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Massachusets Medical Center
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University Health Network
🇨🇦Toronto, Ontario, Canada
Montefiore Medical Center
🇺🇸Bronx, New York, United States