NCT01990456

Brief Summary

Due to lack of studies on mechanical ventilation strategies in patients with severe Acute Respiratory Distress Syndrome (ARDS) supported with Veno-Venous Extra-Corporeal Membrane Oxygenation (VV ECMO), ventilator settings in this patient population are set arbitrarily. In this two-phases prospective, interventional, pilot study we hope to gain physiologically relevant data on two aspects of mechanical ventilation in patients with severe ARDS supported with VV ECMO: (1) the use of tidal ventilation and (2) the level of Positive End-Expiratory Pressure (PEEP).

  1. 1.PHASE 1: impact of tidal ventilation on VILI (10 patients) We hypothesized that a CPAP strategy that minimizes end-tidal pulmonary stress and strain mitigates VILI compared to the current mechanical ventilation practice that employs tidal ventilation in patients with severe ARDS on ECMO.
  2. 2.PHASE 2: impact of PEEP on VILI (10 patients) We also hypothesized that adjusting PEEP to maximize respiratory system compliance reduces VILI in patients with severe ARDS on ECMO.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2013

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 21, 2013

Completed
9 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
Last Updated

November 6, 2014

Status Verified

November 1, 2014

Enrollment Period

1.2 years

First QC Date

November 6, 2013

Last Update Submit

November 5, 2014

Conditions

Keywords

Extracorporeal Membrane OxygenationVentilator-Induced Lung InjuryVentilators, MechanicalPulmonary Heart DiseaseUltrasonography

Outcome Measures

Primary Outcomes (1)

  • Ventilator-Induced Lung Injury (VILI) in patients with ARDS on ECMO ventilated with different strategies (tidal ventilation, CPAP, ZEEP), as measured by Serum Cytokines

    1 hour after initiation of each experimental ventilation strategy

Secondary Outcomes (4)

  • Impact of a CPAP strategy (PEEP set at best compliance and at ZEEP) in patients with severe ARDS on ECMO, as measured by transesophageal echocardiography (TEE)

    30 minutes after initiation of experimental CPAP/ZEEP strategy

  • Feasibility and validity of focused cardiac ultrasound, as compared to TEE as gold standard, in the assessment of RV function in patients with ARDS on ECMO

    30 minutes after initiation of experimental CPAP/ZEEP strategy

  • Feasibility of lung ultrasound in patients with severe ARDS on ECMO

    30 minutes after initiation of experimental CPAP/ZEEP strategy

  • Feasibility (patient recruitment, protocol adherence, physiologic tolerability)

    At overall study completion (i.e., 24 months from study start or after enrolment of last patient)

Study Arms (2)

PHASE 1: impact of tidal ventilation on VILI

EXPERIMENTAL

In the first phase we will test whether administering a distending inspiratory pressure to produce tidal ventilation is superior to a strategy where only continuous positive airway pressure (CPAP) is applied for ventilation induced lung injury (VILI) mitigation, as assessed by its impact on biotrauma (serum cytokines) and physiologic measurements.

Device: PHASE 1: impact of tidal ventilation on VILI

PHASE 2: impact of PEEP on VILI

EXPERIMENTAL

In the second phase we will gain more insight as to whether a strategy that utilizes a PEEP level that correspond to best compliance is beneficial over Zero End-Expiratory Pressure (ZEEP). We will test the impact of both strategies on biotrauma (serum cytokines), physiologic parameters, and right ventricular function (transesophageal echocardiographic assessment).

Device: PHASE 2: impact of PEEP on VILI

Interventions

PHASE 1A - Baseline - Standard Ventilation Protocol (PCV 10 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 1B - CPAP Strategy - CPAP 10 cmH2O for 1 hour PHASE 1C - Higher Tidal Ventilation Strategy (PCV 20 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 1D - Return to Baseline - Standard Ventilation Protocol

PHASE 1: impact of tidal ventilation on VILI

PHASE 2A - Baseline - Standard Ventilation Protocol - (PCV 10 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 2B - Decremental PEEP Trial PHASE 2C - CPAP set at best compliance of respiratory system (as per decremental PEEP Trial) PHASE 2D - ZEEP PHASE 2E - Return to Baseline - Standard Ventilation Protocol

PHASE 2: impact of PEEP on VILI

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Severe ARDS (Berlin Definition)
  • VV ECMO \< 72 hours
  • Endotracheal intubation or tracheostomy

You may not qualify if:

  • Thoracic surgery/lung transplantation during the current hospitalization
  • Contraindications to a RM (MAP \< 60 mmHg despite administration of fluids and vasopressors; Active air leak through a thoracostomy tube; Pneumothorax, or subcutaneous or mediastinal emphysema, (if chest tube has not been inserted))
  • Contraindications to TEE
  • Age \< 16 years

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical Surgical ICU - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Respiratory Distress SyndromeVentilator-Induced Lung InjuryPulmonary Heart Disease

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration DisordersLung InjuryHeart DiseasesCardiovascular Diseases

Study Officials

  • Eddy Fan, MD, PhD

    University Health Network, University of Toronto

    PRINCIPAL INVESTIGATOR
  • Niall D. Ferguson, MD, MSc

    University Health Network, University of Toronto

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Fan Eddy, MD, PhD

CONTACT

Ferguson D. Niall, MD, MSc

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

November 6, 2013

First Posted

November 21, 2013

Study Start

September 1, 2014

Primary Completion

December 1, 2015

Last Updated

November 6, 2014

Record last verified: 2014-11

Locations