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

NCT01681225 | Completed DMC

• 2 other identifiers: 2009P000374UM1HL108724
• Study Type: interventional
• Target: 202
• Locations: 2 countries
• Sites: 14

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

ARDS; mechanical ventilation; ALI; esophageal pressure

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 28

Secondary Outcomes (9)

• Ventilator free days to day 28

  Day 28

• mortality

  Day 60

• lengths of stay

  Day 60

• biomarkers of lung injury

  Day 7

• Survival

  1 year

Study Arms (2)

EPVent

EXPERIMENTAL

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

Control

ACTIVE COMPARATOR

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

Interventions

Esophageal-pressure guided mechanical ventilation OTHER

Also known as: mechanical ventilation strategy, open-lung strategy, EPVent, positive transpulmonary pressure at end-expiration

EPVent

High PEEP mechanical ventilation OTHER

Control

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (14)

University of California at San Diego

La Jolla, California, 92093, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Shock-Trauma University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusets Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

St Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Laval University

Québec, Quebec, G1V 4G5, Canada

Location

Related Publications (12)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Sarge T, Talmor D. Targeting transpulmonary pressure to prevent ventilator induced lung injury. Minerva Anestesiol. 2009 May;75(5):293-9.

  PMID: 19412147 BACKGROUND

• 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 BACKGROUND

• 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 RESULT

• Santarisi A, Suleiman A, Redaelli S, von Wedel D, Beitler JR, Talmor D, Goodspeed V, Jung B, Schaefer MS, Baedorf Kassis E. Transpulmonary Pressure as a Predictor of Successful Lung Recruitment: Reanalysis of a Multicenter International Randomized Clinical Trial. Respir Care. 2025 Jan;70(1):1-9. doi: 10.1089/respcare.11736.

  PMID: 39964867 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Daniel S Talmor, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Edward Lowenstein Professor of Anaesthesia

Study Record Dates

• First Submitted: September 5, 2012
• First Posted: September 7, 2012
• Study Start: October 31, 2012
• Primary Completion: October 12, 2017
• Study Completion: October 19, 2018
• Last Updated: December 3, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); CA (4)