search
Back to results

EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)

Primary Purpose

Acute Respiratory Distress Syndrome

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Esophageal-pressure guided mechanical ventilation
High PEEP mechanical ventilation
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ARDS, mechanical ventilation, ALI, esophageal pressure

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California at San Diego
  • Stanford University Medical Center
  • Orlando Health
  • Shock-Trauma University of Maryland Medical Center
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • University of Massachusets Medical Center
  • University of Michigan
  • Mayo Clinic
  • Montefiore Medical Center
  • Vancouver General Hospital
  • St Joseph's Healthcare
  • University Health Network
  • Laval University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

EPVent

Control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

A composite outcome of mortality and time off the ventilator at 28-days.
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

Ventilator free days to day 28
Number of calendar days breathing unassisted.
mortality
Hospital and ICU mortality to day 60
lengths of stay
Hospital and ICU lengths of stay to days 28 and 60
biomarkers of lung injury
Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
Survival
Mortality to 1 year
Need for rescue therapy
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
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.
Self-reported health assessment
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.
Frailty in patients age 65 and older
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.

Full Information

First Posted
September 5, 2012
Last Updated
December 2, 2019
Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01681225
Brief Title
EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures
Acronym
EPVent2
Official Title
EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
October 31, 2012 (Actual)
Primary Completion Date
October 12, 2017 (Actual)
Study Completion Date
October 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
ARDS, mechanical ventilation, ALI, esophageal pressure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EPVent
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Esophageal-pressure guided mechanical ventilation
Other Intervention Name(s)
mechanical ventilation strategy, open-lung strategy, EPVent, positive transpulmonary pressure at end-expiration
Intervention Type
Other
Intervention Name(s)
High PEEP mechanical ventilation
Primary Outcome Measure Information:
Title
A composite outcome of mortality and time off the ventilator at 28-days.
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.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Ventilator free days to day 28
Description
Number of calendar days breathing unassisted.
Time Frame
Day 28
Title
mortality
Description
Hospital and ICU mortality to day 60
Time Frame
Day 60
Title
lengths of stay
Description
Hospital and ICU lengths of stay to days 28 and 60
Time Frame
Day 60
Title
biomarkers of lung injury
Description
Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
Time Frame
Day 7
Title
Survival
Description
Mortality to 1 year
Time Frame
1 year
Title
Need for rescue therapy
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.
Time Frame
Day 28
Title
Activities of daily living
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.
Time Frame
1 year
Title
Self-reported health assessment
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.
Time Frame
1 year
Title
Frailty in patients age 65 and older
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel S Talmor, MD, MPH
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California at San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Orlando Health
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Shock-Trauma University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Massachusets Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
St Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Laval University
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16236739
Citation
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. doi: 10.1056/NEJMoa050333.
Results Reference
background
PubMed Identifier
12594312
Citation
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003 Feb 20;348(8):683-93. doi: 10.1056/NEJMoa022450.
Results Reference
background
PubMed Identifier
20197533
Citation
Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010 Mar 3;303(9):865-73. doi: 10.1001/jama.2010.218.
Results Reference
background
PubMed Identifier
15269312
Citation
Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.
Results Reference
background
PubMed Identifier
18270352
Citation
Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):637-45. doi: 10.1001/jama.299.6.637.
Results Reference
background
PubMed Identifier
15659948
Citation
Gattinoni L, Caironi P, Carlesso E. How to ventilate patients with acute lung injury and acute respiratory distress syndrome. Curr Opin Crit Care. 2005 Feb;11(1):69-76. doi: 10.1097/00075198-200502000-00011.
Results Reference
background
PubMed Identifier
19001507
Citation
Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11.
Results Reference
background
PubMed Identifier
16540960
Citation
Talmor D, Sarge T, O'Donnell CR, Ritz R, Malhotra A, Lisbon A, Loring SH. Esophageal and transpulmonary pressures in acute respiratory failure. Crit Care Med. 2006 May;34(5):1389-94. doi: 10.1097/01.CCM.0000215515.49001.A2.
Results Reference
background
PubMed Identifier
19412147
Citation
Sarge T, Talmor D. Targeting transpulmonary pressure to prevent ventilator induced lung injury. Minerva Anestesiol. 2009 May;75(5):293-9.
Results Reference
background
PubMed Identifier
25287106
Citation
Fish E, Novack V, Banner-Goodspeed VM, Sarge T, Loring S, Talmor D. The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure. BMJ Open. 2014 Oct 6;4(9):e006356. doi: 10.1136/bmjopen-2014-006356.
Results Reference
background
PubMed Identifier
30776290
Citation
Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs