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

NCT ID: NCT01681225

Last Updated: 2019-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2018-10-19

Brief Summary

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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

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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.

Conditions

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Acute Respiratory Distress Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Esophageal-pressure guided mechanical ventilation

Intervention Type OTHER

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.

Group Type ACTIVE_COMPARATOR

High PEEP mechanical ventilation

Intervention Type OTHER

Interventions

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Esophageal-pressure guided mechanical ventilation

Intervention Type OTHER

High PEEP mechanical ventilation

Intervention Type OTHER

Other Intervention Names

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mechanical ventilation strategy open-lung strategy EPVent positive transpulmonary pressure at end-expiration

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Daniel Talmor

Edward Lowenstein Professor of Anaesthesia

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daniel S Talmor, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

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University of California at San Diego

La Jolla, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Orlando Health

Orlando, Florida, United States

Site Status

Shock-Trauma University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Massachusets Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status

St Joseph's Healthcare

Hamilton, Ontario, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

Site Status

Laval University

Québec, Quebec, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 16236739 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12594312 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20197533 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15269312 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18270352 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15659948 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19001507 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16540960 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 19412147 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25287106 (View on PubMed)

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.

Reference Type RESULT
PMID: 30776290 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39964867 (View on PubMed)

Other Identifiers

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UM1HL108724

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2009P000374

Identifier Type: -

Identifier Source: org_study_id

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