<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03764319</url>
  </required_header>
  <id_info>
    <org_study_id>MUVienna ARDS-ECMO</org_study_id>
    <nct_id>NCT03764319</nct_id>
  </id_info>
  <brief_title>Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With ARDS and ECMO</brief_title>
  <official_title>Low Frequency, Ultra-low Tidal Volume Ventilation in Patients With Severe Acute Respiratory Distress Syndrome and Extracorporeal Membrane Oxygenation: a Prospective, Randomized, Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The acute respiratory distress syndrome (ARDS) is the most severe form of respiratory&#xD;
      failure, presented in 10% of all intensive care patients and carrying a high mortality rate.&#xD;
      Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for patients with severe&#xD;
      ARDS. Mechanical ventilator settings in patients with severe ARDS during ECMO therapy are not&#xD;
      clearly defined at the moment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to assess the effect of a rigorous low breathing frequency and&#xD;
      ultra-low tidal volume ventilation strategy on clinical outcome, compared to standard&#xD;
      ventilator settings following the recent guidelines in patients with severe ARDS treated with&#xD;
      ECMO.&#xD;
&#xD;
      The hypothesis is that a low breathing frequency and ultra-low tidal volume ventilation&#xD;
      strategy is more protective for the ARDS challenged lung and reduces the duration of&#xD;
      mechanical ventilation and so increases the ventilator free days in patients with severe ARDS&#xD;
      treated with ECMO.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Actual">August 1, 2021</completion_date>
  <primary_completion_date type="Actual">August 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Comparison of 2 groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ventilator free days</measure>
    <time_frame>Immediately after initiation of ECMO up to 28 days</time_frame>
    <description>Ventilator free days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time from randomization to fulfillment of extubation criteria</measure>
    <time_frame>Immediately after initiation of ECMO up to 28 days</time_frame>
    <description>Time from randomization (initiation of ECMO) to fulfillment of the extubation criteria:&#xD;
ARDS resolved&#xD;
Temperature ≥ 36°C and ≤ 39°C&#xD;
Low FiO2 (&lt; 0.5)&#xD;
PEEP (&lt; 8 cmH2O) requirement&#xD;
Able to initiate spontaneous breaths&#xD;
Tidalvolume &gt; 5 mL/kg or &gt; 325 mL&#xD;
Minute ventilation 5-6 L/min&#xD;
PaO2/FiO2 &gt; 200 mmHg&#xD;
pH ≥ 7.25&#xD;
Ability to cough after deflating tube cuff&#xD;
Respiratory rate 8-30/min&#xD;
Hemodynamic stability</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total time of mechanical ventilation</measure>
    <time_frame>Start of mechanical ventilation up to 28 days</time_frame>
    <description>Total time of mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28 day mortality</measure>
    <time_frame>Immediately after initiation of ECMO up to 28 days</time_frame>
    <description>Mortality from initiation of ECMO till day 28 after initiation of ECMO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>One year mortality</measure>
    <time_frame>Immediately after initiation of ECMO up to one year</time_frame>
    <description>Mortality from initiation of ECMO till one year after initiation of ECMO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of reintubation</measure>
    <time_frame>Immediately after initiation of ECMO up to 28 days</time_frame>
    <description>Incidence of reintubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>Immediately after initiation of ECMO</time_frame>
    <description>Length of ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of RAS, ACE, ACE2.</measure>
    <time_frame>2 months</time_frame>
    <description>Analyses of leftover blood. Renin angiotensin system (RAS) and Angiotensin converting enzyme (ACE) evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of Cytokines in pg/ml</measure>
    <time_frame>2 months</time_frame>
    <description>IL-6, IL-8, TNFR1, RAGE, Protein C</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>ARDS</condition>
  <condition>Acute Lung Injury</condition>
  <condition>Extracorporeal Membrane Oxygenation</condition>
  <condition>Respiratory Distress Syndrome</condition>
  <condition>Respiratory Tract Diseases</condition>
  <condition>Lung Diseases</condition>
  <condition>Lung Injury, Acute</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ultra-protective ventilator settings in patients with ARDS and ECMO.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard ventilator settings in patients with ARDS and ECMO.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ultra-protective ventilator settings</intervention_name>
    <description>4-5 Breaths per minute; 14-16 cmH2O Positive endexpiratory pressure (PEEP) (adjust PEEP to 23 &lt; Plateau pressure &lt; 25 cmH2O); 23-25 cmH2O Plateau pressure (adjust to not exceed Tidal volume &gt; 4 mL/kg Predicted body weight (PBW)); &lt; 4mL/kg PBW Tidal volume; 1:5 Inspiration:Expiration (I:E)</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard ventilator settings</intervention_name>
    <description>12-25 Breaths per minute; 8-12 cmH2O PEEP; max. 35 cmH2O Plateau pressure</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Moderate to severe ARDS - Partial pressure of oxygen/Fraction of inspired oxygen&#xD;
             (PaO2/FiO2) &lt; 200 mmHg&#xD;
&#xD;
          -  ECMO &lt; 24 hours in situ&#xD;
&#xD;
          -  Gender-matched&#xD;
&#xD;
          -  Age-matched&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 40&#xD;
&#xD;
          -  Expected weaning of ECMO &lt; 3 days (postoperative ECMO)&#xD;
&#xD;
          -  Combustion&#xD;
&#xD;
          -  Restrictive chest wall impairment&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roman Ullrich, Ao.Univ.Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesia and Intensive Care</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna - Division of General Anaesthesia and Intensive Care Medicine</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>September 13, 2021</last_update_submitted>
  <last_update_submitted_qc>September 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Martina Loinger</investigator_full_name>
    <investigator_title>Investigator</investigator_title>
  </responsible_party>
  <keyword>ARDS, ECMO, Ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Respiratory Tract Diseases</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03764319
org study id: MUVienna ARDS-ECMO
nct id: NCT03764319
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The acute respiratory distress syndrome (ARDS) is the most severe form of respiratory
      failure, presented in 10% of all intensive care patients and carrying a high mortality rate.
      Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for patients with severe
      ARDS. Mechanical ventilator settings in patients with severe ARDS during ECMO therapy are not
      clearly defined at the moment.
The aim of this study is to assess the effect of a rigorous low breathing frequency and
      ultra-low tidal volume ventilation strategy on clinical outcome, compared to standard
      ventilator settings following the recent guidelines in patients with severe ARDS treated with
      ECMO.

      The hypothesis is that a low breathing frequency and ultra-low tidal volume ventilation
      strategy is more protective for the ARDS challenged lung and reduces the duration of
      mechanical ventilation and so increases the ventilator free days in patients with severe ARDS
      treated with ECMO.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Comparison of 2 groups
primary purpose: Treatment
masking: None (Open Label)
measure: Ventilator free days
time frame: Immediately after initiation of ECMO up to 28 days
description: Ventilator free days
measure: Time from randomization to fulfillment of extubation criteria
time frame: Immediately after initiation of ECMO up to 28 days
description: Time from randomization (initiation of ECMO) to fulfillment of the extubation criteria:
ARDS resolved
Temperature ≥ 36°C and ≤ 39°C
Low FiO2 (< 0.5)
PEEP (< 8 cmH2O) requirement
Able to initiate spontaneous breaths
Tidalvolume > 5 mL/kg or > 325 mL
Minute ventilation 5-6 L/min
PaO2/FiO2 > 200 mmHg
pH ≥ 7.25
Ability to cough after deflating tube cuff
Respiratory rate 8-30/min
Hemodynamic stability
measure: Total time of mechanical ventilation
time frame: Start of mechanical ventilation up to 28 days
description: Total time of mechanical ventilation
measure: 28 day mortality
time frame: Immediately after initiation of ECMO up to 28 days
description: Mortality from initiation of ECMO till day 28 after initiation of ECMO
measure: One year mortality
time frame: Immediately after initiation of ECMO up to one year
description: Mortality from initiation of ECMO till one year after initiation of ECMO
measure: Incidence of reintubation
time frame: Immediately after initiation of ECMO up to 28 days
description: Incidence of reintubation
measure: Length of ICU stay
time frame: Immediately after initiation of ECMO
description: Length of ICU stay
measure: Evaluation of RAS, ACE, ACE2.
time frame: 2 months
description: Analyses of leftover blood. Renin angiotensin system (RAS) and Angiotensin converting enzyme (ACE) evaluation.
measure: Evaluation of Cytokines in pg/ml
time frame: 2 months
description: IL-6, IL-8, TNFR1, RAGE, Protein C
arm group label: Intervention group
arm group type: Active Comparator
description: Ultra-protective ventilator settings in patients with ARDS and ECMO.
arm group label: Control group
arm group type: Active Comparator
description: Standard ventilator settings in patients with ARDS and ECMO.
intervention type: Other
intervention name: Ultra-protective ventilator settings
description: 4-5 Breaths per minute; 14-16 cmH2O Positive endexpiratory pressure (PEEP) (adjust PEEP to 23 < Plateau pressure < 25 cmH2O); 23-25 cmH2O Plateau pressure (adjust to not exceed Tidal volume > 4 mL/kg Predicted body weight (PBW)); < 4mL/kg PBW Tidal volume; 1:5 Inspiration:Expiration (I:E)
arm group label: Intervention group
intervention type: Other
intervention name: Standard ventilator settings
description: 12-25 Breaths per minute; 8-12 cmH2O PEEP; max. 35 cmH2O Plateau pressure
arm group label: Control group
criteria: 
gender: All
gender based: Yes
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Roman Ullrich, Ao.Univ.Prof.
role: Principal Investigator
affiliation: Department of Anesthesia and Intensive Care
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Martina Loinger
investigator title: Investigator
mesh term: Lung Diseases
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Lung Injury
mesh term: Acute Lung Injury
mesh term: Respiratory Tract Diseases
mesh term: Wounds and Injuries