Clinical trial NCT01681225: EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures
Official title: EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures (EPVent2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Keywords: ARDS
mechanical ventilation
ALI
esophageal pressure
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-09-07
Enrollment: 202
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: A composite outcome of mortality and time off the ventilator at 28-days.
timeFrame: Day 28
Secondary outcomes:
measure: Ventilator free days to day 28
timeFrame: Day 28
measure: mortality
timeFrame: Day 60
measure: lengths of stay
timeFrame: Day 60
measure: biomarkers of lung injury
timeFrame: Day 7
measure: Survival
timeFrame: 1 year
measure: Need for rescue therapy
timeFrame: Day 28
measure: Activities of daily living
timeFrame: 1 year
measure: Self-reported health assessment
timeFrame: 1 year
measure: Frailty in patients age 65 and older
timeFrame: 1 year
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Baltimore
country: United States
facility: Shock-Trauma University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusets Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: St Joseph's Healthcare
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Quebec City
country: Canada
facility: Laval University
state: Quebec
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Daniel S Talmor, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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: 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: 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: 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: 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: Sarge T, Talmor D. Targeting transpulmonary pressure to prevent ventilator induced lung injury. Minerva Anestesiol. 2009 May;75(5):293-9.
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: 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.