<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/NCT04429399</url>
  </required_header>
  <id_info>
    <org_study_id>6011</org_study_id>
    <nct_id>NCT04429399</nct_id>
  </id_info>
  <brief_title>Lowering PEEP: Weaning From High PEEP Setting</brief_title>
  <official_title>Effects of Positive End Expiratory Pressure (PEEP) Decrease in Patient With Acute Respiratory Distress Syndrome (ARDS) Ventilated According to High PEEP Strategy (ExPress Trial).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bari</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 perfusion of the deeply different areas coexisting in ARDS lung generates two type of&#xD;
      venus-admixure : true shunt and shunt effect. Briefly, true shunt and shunt effect are&#xD;
      related to non-aerated and poorly-ventilated lung areas perfusion respectively. Practically,&#xD;
      it is not possible to quantify the true shunt and the shunt-effect directly, but we can&#xD;
      measure the &quot;total-shunt&quot;, i.e. the sum of two kind of venus-admixured. As it is known from&#xD;
      classical physiology, the effects of FiO2 variations on PaO2 are deeply different depending&#xD;
      on the type of venous admixures. In the case of a patient with virtually only true shunt, any&#xD;
      FiO2 variation will not modify the PaO2. On the other hand, in a patient with virtually only&#xD;
      a shunt effect, increasing the FiO2 the PaO2 will progressively increase. Indeed, ventilating&#xD;
      a patient presenting only a shunt effect (without true shunt) with pure oxygen will generate&#xD;
      a &quot;normal&quot; P/F ratio. In patients ventilated with high PEEP levels it is difficult to predict&#xD;
      based on the P/F ratio the relative amount of true shunt and shunt effect. However, patients&#xD;
      presenting a significant shunt effect when ventilated with higher PEEP level would likely&#xD;
      have &quot;unstable&quot; poorly aerated lung areas that need PEEP to remain opened. In those patients,&#xD;
      a PEEP-weaning protocol based on the P/F ratio could induce significant alveolar&#xD;
      de-recruitment and clinical deterioration. On the contrary, patients with less shunt effect&#xD;
      would be likely less prone to alveolar de-recruitment and would benefice from PEEP decrease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      the investigators set up a study to test the hypothesis that patients presenting a&#xD;
      significant shunt effect when ventilated with higher PEEP levels could be prone to&#xD;
      significant alveolar de-recruitment at the PEEP weaning attempt. To do so, the investigator&#xD;
      has to measure the total shunt at higher PEEP level in patients ready to be weaned from the&#xD;
      PEEP (according to the Mercat protocol), at three FiO2 levels (i.e. 0,3, 0,6 and 1). The&#xD;
      shunt effect is quantified as the difference in total shunt between FiO2 0,3 and .The&#xD;
      hypothesis of this study is that the shunt effect could predict alveolar de-recruitment when&#xD;
      weaning PEEP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2019</start_date>
  <completion_date type="Actual">January 1, 2022</completion_date>
  <primary_completion_date type="Actual">June 21, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>de-recruitment</measure>
    <time_frame>decreasing PEEP from high to low levelthrough study completion, an average of 2 years</time_frame>
    <description>the shunt effect cold predict the lung de-recruitment volume</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Mechanical Ventilation Complication</condition>
  <arm_group>
    <arm_group_label>High positive end-expiratory pressure Ventilation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patient ventilated fixing high level of positive end expiratory pressure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low positive end-expiratory pressure Ventilation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>patient ventilated fixing low level of positive end expiratory pressure</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>decrease the positive end expiratory pressure (PEEP)</intervention_name>
    <description>decrease the PEEP going from high (according to ExPress Trial) to low level</description>
    <arm_group_label>High positive end-expiratory pressure Ventilation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>mechanical features assessment</intervention_name>
    <description>evaluation of the mechanical features of respiratory system</description>
    <arm_group_label>High positive end-expiratory pressure Ventilation</arm_group_label>
    <arm_group_label>Low positive end-expiratory pressure Ventilation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>shunt assessment</intervention_name>
    <description>evaluation of the pulmonary shunt during two different ventilation setting</description>
    <arm_group_label>High positive end-expiratory pressure Ventilation</arm_group_label>
    <arm_group_label>Low positive end-expiratory pressure Ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age major than 18&#xD;
&#xD;
          -  1-2 days since the beginning of mechanical ventilation&#xD;
&#xD;
          -  Moderate or severe ARDS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a story of chronic obstructive pulmonary disease (COPD)&#xD;
&#xD;
          -  Patients with asthma&#xD;
&#xD;
          -  Patients with neurological disease&#xD;
&#xD;
          -  Patients with heart disease&#xD;
&#xD;
          -  Patients with cardiopulmonary.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Policlinico</name>
      <address>
        <city>Bari</city>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>January 20, 2022</last_update_submitted>
  <last_update_submitted_qc>January 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bari</investigator_affiliation>
    <investigator_full_name>Salvatore Grasso</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <!-- 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/NCT04429399
org study id: 6011
nct id: NCT04429399
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The perfusion of the deeply different areas coexisting in ARDS lung generates two type of
      venus-admixure : true shunt and shunt effect. Briefly, true shunt and shunt effect are
      related to non-aerated and poorly-ventilated lung areas perfusion respectively. Practically,
      it is not possible to quantify the true shunt and the shunt-effect directly, but we can
      measure the "total-shunt", i.e. the sum of two kind of venus-admixured. As it is known from
      classical physiology, the effects of FiO2 variations on PaO2 are deeply different depending
      on the type of venous admixures. In the case of a patient with virtually only true shunt, any
      FiO2 variation will not modify the PaO2. On the other hand, in a patient with virtually only
      a shunt effect, increasing the FiO2 the PaO2 will progressively increase. Indeed, ventilating
      a patient presenting only a shunt effect (without true shunt) with pure oxygen will generate
      a "normal" P/F ratio. In patients ventilated with high PEEP levels it is difficult to predict
      based on the P/F ratio the relative amount of true shunt and shunt effect. However, patients
      presenting a significant shunt effect when ventilated with higher PEEP level would likely
      have "unstable" poorly aerated lung areas that need PEEP to remain opened. In those patients,
      a PEEP-weaning protocol based on the P/F ratio could induce significant alveolar
      de-recruitment and clinical deterioration. On the contrary, patients with less shunt effect
      would be likely less prone to alveolar de-recruitment and would benefice from PEEP decrease.
the investigators set up a study to test the hypothesis that patients presenting a
      significant shunt effect when ventilated with higher PEEP levels could be prone to
      significant alveolar de-recruitment at the PEEP weaning attempt. To do so, the investigator
      has to measure the total shunt at higher PEEP level in patients ready to be weaned from the
      PEEP (according to the Mercat protocol), at three FiO2 levels (i.e. 0,3, 0,6 and 1). The
      shunt effect is quantified as the difference in total shunt between FiO2 0,3 and .The
      hypothesis of this study is that the shunt effect could predict alveolar de-recruitment when
      weaning PEEP.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: de-recruitment
time frame: decreasing PEEP from high to low levelthrough study completion, an average of 2 years
description: the shunt effect cold predict the lung de-recruitment volume
arm group label: High positive end-expiratory pressure Ventilation
arm group type: Other
description: patient ventilated fixing high level of positive end expiratory pressure
arm group label: Low positive end-expiratory pressure Ventilation
arm group type: Other
description: patient ventilated fixing low level of positive end expiratory pressure
intervention type: Other
intervention name: decrease the positive end expiratory pressure (PEEP)
description: decrease the PEEP going from high (according to ExPress Trial) to low level
arm group label: High positive end-expiratory pressure Ventilation
intervention type: Other
intervention name: mechanical features assessment
description: evaluation of the mechanical features of respiratory system
arm group label: High positive end-expiratory pressure Ventilation
arm group label: Low positive end-expiratory pressure Ventilation
intervention type: Other
intervention name: shunt assessment
description: evaluation of the pulmonary shunt during two different ventilation setting
arm group label: High positive end-expiratory pressure Ventilation
arm group label: Low positive end-expiratory pressure Ventilation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Bari
investigator full name: Salvatore Grasso
investigator title: Associate Professor