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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Daniel Talmor, Beth Israel Deaconess Medical Center
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Daniel Talmor, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01681225
First received: September 5, 2012
Last updated: April 11, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention
Acute Respiratory Distress Syndrome Other: Esophageal-pressure guided mechanical ventilation Other: High PEEP mechanical ventilation

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)

Resource links provided by NLM:


Further study details as provided by Daniel Talmor, Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • 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 in the treatment group is compared to every subject in the control group and assigned one number resulting from each comparison. Since mortality outcome is clinically more important, mortality takes precedence over days off the ventilator. These scores are summed up to obtain a cumulative score for each subject. The cumulative scores are added up for each treatment group to form a test statistic by the Mann-Whitney technique.


Secondary Outcome Measures:
  • Ventilator free days to day 28 [ Time Frame: Day 28 ]
  • mortality [ Time Frame: Day 60 ]
    Hospital and ICU mortality to days 28 and 60

  • lengths of stay [ Time Frame: Day 60 ]
    Hospital and ICU lengths of stay to days 28 and 60

  • biomarkers of lung injury [ Time Frame: Day 7 ]
    Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment

  • Survival [ Time Frame: 1 year ]
  • Quality of life [ Time Frame: 1 year ]
    Will assess via questionnaires (SF-12, Barthel Index, VES-13) done by phone at 12 months

  • Need for rescue therapy [ Time Frame: 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.


Estimated Enrollment: 200
Study Start Date: September 2012
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPVent
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.
Other: Esophageal-pressure guided mechanical ventilation
Other Names:
  • mechanical ventilation strategy
  • open-lung strategy
  • EPVent
  • positive transpulmonary pressure at end-expiration
Active Comparator: Control
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.
Other: High PEEP mechanical ventilation

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.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681225

Contacts
Contact: Daniel S Talmor, MD, MPH 617-667-2902 dtalmor@bidmc.harvard.edu
Contact: Valerie M Banner-Goodspeed, MPH 617-667-5045 vgoodspe@bidmc.harvard.edu

Locations
United States, California
University of California at San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Jeremy R Beitler, MD MPH       jbeitler@ucsd.edu   
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Joseph Levitt, MD       jlevitt@stanford.edu   
United States, Florida
Orlando Health Terminated
Orlando, Florida, United States, 32806
United States, Maryland
Shock-Trauma University of Maryland Medical Center Terminated
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital Terminated
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital Withdrawn
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Todd Sarge, MD    617-667-3112    tsarge@bidmc.harvard.edu   
Principal Investigator: Todd Sarge, MD         
University of Massachusets Medical Center Terminated
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Pauline Park, MD       parkpk@umich.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Richard Oeckler, MD       Oeckler.Richard@mayo.edu   
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Principal Investigator: Michelle Gong, MD, MS         
United States, Ohio
University of Cincinnati Withdrawn
Cincinnati, Ohio, United States, 45267
Canada, British Columbia
Vancouver General Hospital Terminated
Vancouver, British Columbia, Canada
Canada, Ontario
St Joseph's Healthcare Recruiting
Hamilton, Ontario, Canada, L8N 4A6
Contact: Deborah Cook, MD       debcook@mcmaster.ca   
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Eddy Fan, MD       eddy.fan@uhn.ca   
Canada, Quebec
Laval University Recruiting
Quebec City, Quebec, Canada, G1V 4G5
Contact: François Lellouche, MD       Francois.Lellouche@criucpq.ulaval.ca   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Daniel S Talmor, MD, MPH Beth Israel Deaconess Medical Center
  More Information

Additional Information:
Publications:

Responsible Party: Daniel Talmor, Edward Lowenstein Professor of Anaesthesia, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01681225     History of Changes
Other Study ID Numbers: 2009P000374
UM1HL108724 ( U.S. NIH Grant/Contract )
Study First Received: September 5, 2012
Last Updated: April 11, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel Talmor, Beth Israel Deaconess Medical Center:
ARDS
mechanical ventilation
ALI
esophageal pressure

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury

ClinicalTrials.gov processed this record on September 18, 2017