title: The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure.
abstract: BACKGROUND
  Optimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS.
  
  
  METHODS
  EPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTP values will result in improved mortality and ventilator-free days.
  
  
  BACKGROUND
  Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy.
  
  
  BACKGROUND
  ClinicalTrials.gov under number NCT01681225.
authors.affiliation: Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Fish
authors.affiliation: Soroka University Medical Center, Rager Boulevard, Beer-Sheva, Israel.
authors.forename: Victor
authors.initials: V
authors.lastname: Novack
authors.affiliation: Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.|Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Banner-Goodspeed
authors.affiliation: Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Sarge
authors.affiliation: Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Loring
authors.affiliation: Department of Anesthesia, Critical Care, & Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Talmor
mesh_terms: D000328:Adult; D002985:Clinical Protocols; D004947:Esophagus / Q000503:physiopathology; D005260:Female; D006801:Humans; D059725:Interactive Ventilatory Support / Q000009:adverse effects / Q000379:methods*; D008168:Lung / Q000503:physiopathology; D008297:Male; D012128:Respiratory Distress Syndrome / Q000503:physiopathology / Q000628:therapy; D016896:Treatment Outcome
keywords: acute lung injury; acute respiratory distress syndrome; clinical trial; esophageal balloon; transpulmonary pressure