<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01681225</url>
  </required_header>
  <id_info>
    <org_study_id>2009P000374</org_study_id>
    <secondary_id>UM1HL108724</secondary_id>
    <nct_id>NCT01681225</nct_id>
  </id_info>
  <brief_title>EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures</brief_title>
  <acronym>EPVent2</acronym>
  <official_title>EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II multi-centered, randomized controlled trial of mechanical ventilation directed&#xD;
      by esophageal pressure measurement will test the primary hypothesis that using a strategy of&#xD;
      maintaining a minimal but positive transpulmonary pressure (Ptp = airway pressure minus&#xD;
      pleural pressure) throughout the ventilatory cycle will lead to an improvement in patient&#xD;
      survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This phase II prospective randomized controlled trial of ventilation directed by esophageal&#xD;
      pressure measurements will enroll 200 patients with moderate to severe ARDS by the Berlin&#xD;
      conference definition in several academic medical centers in North America. The control group&#xD;
      will be ventilated using an alternative high-PEEP strategy with PEEP and FiO2 set using to an&#xD;
      empiric table.&#xD;
&#xD;
      Plasma samples will be obtained at enrollment and days 3 and 7 and assessed for a variety of&#xD;
      lung injury biomarkers to better assess the association between our intervention and the&#xD;
      inflammation associated with mechanical ventilation and the development of ARDS. Hospital&#xD;
      survivors will undergo a brief follow up phone survey to assess survival, functional status&#xD;
      (Barthel Index), health-related QOL (Short Form 12), and frailty (VES) twelve months after&#xD;
      enrollment.&#xD;
&#xD;
      The study length will be six years with a six month start-up period followed by a planned 50&#xD;
      month enrollment and twelve month follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2012</start_date>
  <completion_date type="Actual">October 19, 2018</completion_date>
  <primary_completion_date type="Actual">October 12, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A composite outcome of mortality and time off the ventilator at 28-days.</measure>
    <time_frame>Day 28</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilator free days to day 28</measure>
    <time_frame>Day 28</time_frame>
    <description>Number of calendar days breathing unassisted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>Day 60</time_frame>
    <description>Hospital and ICU mortality to day 60</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lengths of stay</measure>
    <time_frame>Day 60</time_frame>
    <description>Hospital and ICU lengths of stay to days 28 and 60</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biomarkers of lung injury</measure>
    <time_frame>Day 7</time_frame>
    <description>Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Mortality to 1 year</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for rescue therapy</measure>
    <time_frame>Day 28</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activities of daily living</measure>
    <time_frame>1 year</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported health assessment</measure>
    <time_frame>1 year</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frailty in patients age 65 and older</measure>
    <time_frame>1 year</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">202</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>EPVent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The overall goals for the &quot;EPVent&quot; 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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Esophageal-pressure guided mechanical ventilation</intervention_name>
    <arm_group_label>EPVent</arm_group_label>
    <other_name>mechanical ventilation strategy</other_name>
    <other_name>open-lung strategy</other_name>
    <other_name>EPVent</other_name>
    <other_name>positive transpulmonary pressure at end-expiration</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High PEEP mechanical ventilation</intervention_name>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute onset of ARDS as defined by the Berlin Consensus Conference definitions:&#xD;
&#xD;
               1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio &lt; 200 mmHg&#xD;
&#xD;
               2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not&#xD;
                  present for more than 7 days&#xD;
&#xD;
               3. Respiratory failure not fully explained by cardiac failure or fluid overload&#xD;
&#xD;
               4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O&#xD;
&#xD;
          -  Age 16 years or older&#xD;
&#xD;
          -  Duration of ARDS 36 hours or less from meeting final Berlin criterion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received mechanical ventilation more than 96 hours&#xD;
&#xD;
          -  Recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal&#xD;
             trauma, recent esophageal surgery or other contraindication for nasogastric tube&#xD;
             placement&#xD;
&#xD;
          -  Severe coagulopathy (platelet count &lt; 5000/microliter or INR &gt; 4)&#xD;
&#xD;
          -  History of lung transplantation&#xD;
&#xD;
          -  Elevated intracranial pressure or conditions where hypercapnia-induced elevations in&#xD;
             intracranial pressure should be avoided&#xD;
&#xD;
          -  Evidence of active air leak from the lung&#xD;
&#xD;
          -  not committed to full support&#xD;
&#xD;
          -  Participation in other intervention trials for ARDS or for sepsis within the past 30&#xD;
             days.&#xD;
&#xD;
          -  Neuromuscular disease that impairs ability to ventilate spontaneously&#xD;
&#xD;
          -  Severe chronic liver disease, defined as Child-Pugh Score of ≥12&#xD;
&#xD;
          -  Treating clinician refusal, or unwillingness to commit to controlled ventilation for&#xD;
             at least 24 hours&#xD;
&#xD;
          -  Inability to get informed consent from the patient or surrogate.&#xD;
&#xD;
          -  Use of rescue therapies for prior to enrollment (e.g. nitric oxide, ECMO, prone&#xD;
             positioning, high frequency oscillation). This does not exclude cases where these&#xD;
             therapies were used as the initial mode of ventilation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel S Talmor, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California at San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shock-Trauma University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusets Medical Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Joseph's Healthcare</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 4A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laval University</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>16236739</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>12594312</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20197533</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>15269312</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>18270352</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>15659948</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19001507</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>16540960</PMID>
  </reference>
  <reference>
    <citation>Sarge T, Talmor D. Targeting transpulmonary pressure to prevent ventilator induced lung injury. Minerva Anestesiol. 2009 May;75(5):293-9.</citation>
    <PMID>19412147</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>25287106</PMID>
  </reference>
  <results_reference>
    <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.</citation>
    <PMID>30776290</PMID>
  </results_reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>December 2, 2019</last_update_submitted>
  <last_update_submitted_qc>December 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Daniel Talmor</investigator_full_name>
    <investigator_title>Edward Lowenstein Professor of Anaesthesia</investigator_title>
  </responsible_party>
  <keyword>ARDS</keyword>
  <keyword>mechanical ventilation</keyword>
  <keyword>ALI</keyword>
  <keyword>esophageal pressure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01681225
org study id: 2009P000374
secondary id: UM1HL108724
nct id: NCT01681225
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: A composite outcome of mortality and time off the ventilator at 28-days.
time frame: Day 28
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.
measure: Ventilator free days to day 28
time frame: Day 28
description: Number of calendar days breathing unassisted.
measure: mortality
time frame: Day 60
description: Hospital and ICU mortality to day 60
measure: lengths of stay
time frame: Day 60
description: Hospital and ICU lengths of stay to days 28 and 60
measure: biomarkers of lung injury
time frame: Day 7
description: Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment
measure: Survival
time frame: 1 year
description: Mortality to 1 year
measure: Need for rescue therapy
time frame: Day 28
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.
measure: Activities of daily living
time frame: 1 year
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.
measure: Self-reported health assessment
time frame: 1 year
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.
measure: Frailty in patients age 65 and older
time frame: 1 year
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.
arm group label: EPVent
arm group type: Experimental
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 group label: Control
arm group type: Active Comparator
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: Esophageal-pressure guided mechanical ventilation
arm group label: EPVent
other name: mechanical ventilation strategy
other name: open-lung strategy
other name: EPVent
other name: positive transpulmonary pressure at end-expiration
intervention type: Other
intervention name: High PEEP mechanical ventilation
arm group label: Control
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel S Talmor, MD, MPH
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: Canada
country: United States
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.
PMID: 16236739
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.
PMID: 12594312
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.
PMID: 20197533
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.
PMID: 15269312
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.
PMID: 18270352
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.
PMID: 15659948
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.
PMID: 19001507
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.
PMID: 16540960
citation: Sarge T, Talmor D. Targeting transpulmonary pressure to prevent ventilator induced lung injury. Minerva Anestesiol. 2009 May;75(5):293-9.
PMID: 19412147
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.
PMID: 25287106
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.
PMID: 30776290
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Daniel Talmor
investigator title: Edward Lowenstein Professor of Anaesthesia
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
sharing ipd: No