EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures

Not Applicable

Completed

• Conditions: Acute Respiratory Distress Syndrome

• 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.

Study Timeline

• Study First Submitted: 2012-09-05
• Study First Submitted QC: 2012-09-05
• Study First Posted: 2012-09-07
• Study Start: 2012-10-31
• Primary Completion: 2017-10-12
• Study Completion: 2018-10-19
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-02
• Last Update Posted: 2019-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 202

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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
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.
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.
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

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Massachusets Medical Center; 🇺🇸 Worcester, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

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