EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Acute Respiratory Distress Syndrome
- Sponsor
- Beth Israel Deaconess Medical Center
- Enrollment
- 202
- Locations
- 14
- Primary Endpoint
- A composite outcome of mortality and time off the ventilator at 28-days.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Daniel Talmor
Edward Lowenstein Professor of Anaesthesia
Beth Israel Deaconess Medical Center
Eligibility Criteria
Inclusion Criteria
- •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.
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
Outcomes
Primary Outcomes
A composite outcome of mortality and time off the ventilator at 28-days.
Time Frame: 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 Outcomes
- lengths of stay(Day 60)
- Ventilator free days to day 28(Day 28)
- mortality(Day 60)
- biomarkers of lung injury(Day 7)
- Survival(1 year)
- Need for rescue therapy(Day 28)
- Activities of daily living(1 year)
- Frailty in patients age 65 and older(1 year)
- Self-reported health assessment(1 year)