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

Acute Respiratory Distress Syndrome Clinical Trial

— EPVent2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01681225
• Other study ID #: 2009P000374
• Secondary ID: UM1HL108724
• Status: Completed
• Phase: N/A
• Start date: October 31, 2012
• Est. completion date: October 19, 2018

Study information

• Verified date: December 2019
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: October 19, 2018
• Est. primary completion date: October 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• Esophageal-pressure guided mechanical ventilation

• High PEEP mechanical ventilation

Locations

Country	Name	City	State
Canada	St Joseph's Healthcare	Hamilton	Ontario
Canada	Laval University	Quebec City	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	University of Michigan	Ann Arbor	Michigan
United States	Shock-Trauma University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of California at San Diego	La Jolla	California
United States	Orlando Health	Orlando	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University Medical Center	Stanford	California
United States	University of Massachusets Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (11)

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 — View 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. Review. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View Citation

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

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Ventilator free days to day 28	Number of calendar days breathing unassisted.	Day 28
Secondary	mortality	Hospital and ICU mortality to day 60	Day 60
Secondary	lengths of stay	Hospital and ICU lengths of stay to days 28 and 60	Day 60
Secondary	biomarkers of lung injury	Plasma biomarkers of lung injury on enrollment and days 3 and 7 after enrollment	Day 7
Secondary	Survival	Mortality to 1 year	1 year
Secondary	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.	Day 28
Secondary	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.	1 year
Secondary	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.	1 year
Secondary	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.	1 year