<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/NCT04503876</url>
  </required_header>
  <id_info>
    <org_study_id>RBHP 2019 GODET (Peep Réa)</org_study_id>
    <nct_id>NCT04503876</nct_id>
  </id_info>
  <brief_title>Effects of End-expiratory Positive Pressure Optimization in Intubated Patients With Healthy Lung or Acute Respiratory Distress Syndrome</brief_title>
  <acronym>PEEP-Réa</acronym>
  <official_title>Pulmonary and Ventilatory Effects of End-expiratory Positive Pressure Optimization in Intubated ICU Patients With Healthy Lungs or Acute Respiratory Distress Syndrome. A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <oversight_info>
    <has_dmc>No</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>
      PEEP titration is a recommended during invasive mechanical ventilation of ICU patients.&#xD;
      However, little is known about the right way to conduct this titration. PEEP titration can be&#xD;
      conducted by a stepwise increase in PEEP level, or following an ARM and a consecutive&#xD;
      stepwise decrease in PEEP level. Those 2 methods will be explored in intubated ICU patients&#xD;
      either with healthy lung or ARDS lungs. Physiological exploration will include end-expiratory&#xD;
      lung volume measurements, driving pressure, compliance and electro-impedance tomography at&#xD;
      each PEEP level.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Management of ICU patients may require the use of ventilatory support requiring tracheal&#xD;
      intubation and invasive mechanical ventilation.&#xD;
&#xD;
      Any mechanically ventilated patient is exposed to the formation of atelectasis (collapsed&#xD;
      pulmonary alveoli), which occurs systematically after endotracheal tube insertion, after any&#xD;
      de-recruiting action (tracheal suction, disconnection) or simply if protective ventilation is&#xD;
      used, combining small tidal volumes (6 to 8 mL/kg of theoretical ideal body weight - IBW) and&#xD;
      an end-expiratory positive pressure (PEEP) that is sometimes insufficient. It is thus&#xD;
      proposed to perform alveolar recruitment maneuvers (ARMs), which remove atelectasis by&#xD;
      temporarily increasing intrathoracic pressure. To avoid alveolar re-collapse, it is necessary&#xD;
      to apply a sufficient level of PEEP.&#xD;
&#xD;
      The opening pressure (P) necessary for the re-expansion of a collapsed alveolus is inversely&#xD;
      proportional to its radius (r), following Laplace law P = 2.γ/r where γ is the surface&#xD;
      tension. The pressure necessary to the re-expansion of a collapsed cell depends on its&#xD;
      radius. Amato's team has showed in 2006 that within the same lung, several levels of alveolar&#xD;
      aeration and thus several opening pressures coexist. The distribution of pressures was&#xD;
      bimodal, with a peak around 30 cmH2O and a second around 40 cmH2O. Consequently, to allow&#xD;
      complete re-expansion of atelectasis within a lung, it is necessary to apply a pressure at&#xD;
      least equal to 30 cmH2O. The application of insufficient pressures cannot be expected to&#xD;
      result in complete re-expansion of the lung, but rather in an increase in aeration of already&#xD;
      aerated alveoli (whose radius is larger and whose opening pressure is much lower), what, in&#xD;
      turn, can lead to over-distension. This is probably what can happen if the PEEP is increased&#xD;
      without any previous ARM.&#xD;
&#xD;
      The application of an ARM can also lead to an overdistension phenomenon during a reduced&#xD;
      period of time (20 to 30 seconds), contrary to the direct application of a high PEEP which&#xD;
      could led to an overdistension lasting a much longer period of time (possibly several hours)&#xD;
      and aggravated with each administration of a tidal volume (and thus several times per&#xD;
      minute). Chronic lung exposure to overdistension phenomena can induce a disintegration of&#xD;
      alveolar collagen fibers (volotrauma), leading to local inflammation (biotrauma) and systemic&#xD;
      inflammation by releasing pro-inflammatory molecules (cytokines...) into the bloodstream and&#xD;
      led to apoptosis in distant organs (kidney, digestive tract for example).&#xD;
&#xD;
      The optimization of mechanical ventilation requires the search for the optimal PEEP:&#xD;
      insufficient, it cannot prevent atelectasis formation; too high, it would lead to alveolar&#xD;
      overdistension. In current practice, the PEEP is determined arbitrary or following a stepwise&#xD;
      titration, either by incremental or decremental steps. To date, scientific literature is not&#xD;
      unequivocal concerning the use of ARMs and their safety. Thus, some teams prefer not to use&#xD;
      ARMs and usually apply an upward PEEP level.&#xD;
&#xD;
      The concepts presented above are valid both in patients with healthy lungs and in patients&#xD;
      with &quot;sick&quot; lungs, the archetype and most severe form of which is acute respiratory distress&#xD;
      syndrome (ARDS), which is a frequent pathology in ICU (10 to 20% of patients admitted). Its&#xD;
      definition is based on the Berlin criteria published in 2012. The morality varies between 30&#xD;
      and 40% depending on the severity of the respiratory impairment. Management of patients&#xD;
      suffering from ARDS requires an optimization of oxygenation, which is based first of all on&#xD;
      mechanical ventilation, whether invasive or not. Since the ARDS Network study published in&#xD;
      2000 in the New England Journal of Medicine, it has been globally accepted that tidal volumes&#xD;
      should be reduced to no more than 6 mL/kg IBW. Ventilatory management is based on concepts of&#xD;
      &quot;baby lung&quot; and &quot;open lung&quot;. These concepts explain that it is mandatory to consider that the&#xD;
      lung volume available for mechanical ventilation is very small compared to the healthy lung&#xD;
      volume (baby lung) and that the reduction in tidal volume must be accompanied by adjustments&#xD;
      to keep the lung &quot;open&quot;, combating the formation of atelectasis by the use of sufficient PEEP&#xD;
      and ARMs.&#xD;
&#xD;
      Far from this pulmonary pathology, any mechanically ventilated patient, whether in the ICU or&#xD;
      operating theatre, must benefit from a protective strategy. Any inadequate adjustment of the&#xD;
      ventilation parameters can lead to lung lesions induced by mechanical ventilation (VILI,&#xD;
      Ventilator Induced Lung Injuries) and to lesions similar to those observed during ARDS.&#xD;
&#xD;
      We therefore propose to explore the impact on pulmonary aeration and ventilatory parameters&#xD;
      of two different strategies of PEEP optimization during invasive mechanical ventilation in&#xD;
      healthy lungs and ARDS ICU patients. This randomized controlled study would allow us to&#xD;
      validate our hypotheses, depending on the respiratory mechanics and patient's pulmonary&#xD;
      disease.The final aim of this study is to determine the effects of a strategy based on the&#xD;
      application of an ARM followed by decremental PEEP titration, compared to an incremental PEEP&#xD;
      strategy without ARM, on pulmonary and ventilatory physio-(patho)-logical parameters in ICU&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 12, 2019</start_date>
  <completion_date type="Anticipated">October 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 12, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>Interventional trial comparing two strategies of PEEP optimization during mechanical ventilation in two groups of ICU patients: with healthy lungs or with ARDS. The study consists of comparing pulmonary pathophysiological parameters for different PEEP levels. The first strategy implies the use of an ARM followed by a stepwise decremental PEEP titration whereas the second considers a stepwise incremental PEEP titration without any previous ARM, during controlled invasive mechanical ventilation. Each patient will receive both strategies in a random consecutive order</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Statistical analysis will be conducted by an independant statistician not involved in data collection</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Recruited lung volume at each PEEP level between the 2 strategies (incremental or decremental).</measure>
    <time_frame>The last minute of each Peep Step</time_frame>
    <description>: The main endpoint is the difference between the recruited lung volume measured by nitrogen washin-washout method at the end of each PEEP level (5th minute) with the basal value measured at the beginning of the protocol, between decremental and incremental stepwise PEEP titration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Homogeneity of pulmonary aeration</measure>
    <time_frame>The last minute of each Peep Step</time_frame>
    <description>Evaluation by using the Electrical Impedance Tomography (EIT) - derived index Center of ventilation (CoV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Homogeneity of pulmonary aeration</measure>
    <time_frame>The last minute of each Peep Step</time_frame>
    <description>Evaluation by using the Global Inhomogeneity index (GI) by electro-impedance tomography (EIT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional impedance variation</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of regional impedance variation (TIV: Tidal Impedance Variation) by EIT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atelectrauma</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Assessement of atelectrauma (RVD: Regional Ventilation Delay) by EIT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung volume variations</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of lung volume variations by EIT (EELI : End Expiratory Lung Impedance)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical power delivered Mechanical power delivered</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>By using the formula : Power rs =RR⋅{ΔV² ⋅[1/2 ⋅ELrs +RR⋅((1+I:E) / (60⋅I:E) x Raw ]+ΔV⋅PEEP}. (Gattinoni, Intensive Care Medicine 2016)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alveolar strain</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Alveolar strain as assessed by TV/FRC where TV stands for tidal volume and FRC functional residual capacity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recruited lung volume</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of recruited lung volumes (Dellamonica, Intensive Care Medicine 2011)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory dead space</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Ventilatory dead space = Vd/Vt. Where Vd is the dead space volume and Vt is the tidal volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory parameters</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of the compliance = TV / (Pplat - PEEP) where TV stands for tidal volume, Pplat stands for Plateau Pressure and PEEP stands for Positive End-Expiratory Pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory parameters</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of the driving pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory parameters</measure>
    <time_frame>Measurement during the last minute of each PEEP step</time_frame>
    <description>Evaluation of the plateau pressure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>ICU Patients</condition>
  <condition>Healthy Lung</condition>
  <condition>Positive End-Expiratory Pressure</condition>
  <condition>ARDS</condition>
  <condition>Alveolar Recruitment Maneuver</condition>
  <arm_group>
    <arm_group_label>Decremental PEEP titration following an ARM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PEEP will be titrated in a stepwise decremental fashion following a standardized alveolar recruitment maneuver (ARM). The ARM is a progressive increase of intra-thoracic pressure (pressure controlled mode), with a constant driving pressure of 10 cmH2O and PEEP steps (10-15-20-25-30-35 and 40 cmH2O), reaching a maximum pressure of 50 cmH2O, allowing full recruitment. PEEP steps will be conducted every 2 cmH2O (from 20 to 6 cmH2O), every 5 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Incremental PEEP titration without any previous ARM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>PEEP will be titrated in a stepwise incremental fashion without any previous alveolar recruitment maneuver (ARM). PEEP steps will be conducted every 2 cmH2O (from 6 to 20 cmH2O), every 5 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Increasing PEEP setting</intervention_name>
    <description>End expiratory lung volume and lung aeration measurements will be conducted using electrical impedance tomography and nitrogen washin-washout method. Measurements will be conducted during the last minute of each step.</description>
    <arm_group_label>Incremental PEEP titration without any previous ARM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Decreasing PEEP setting</intervention_name>
    <description>End expiratory lung volume and lung aeration measurements will be conducted using electrical impedance tomography and nitrogen washin-washout method. Measurements will be conducted during the last minute of each step.</description>
    <arm_group_label>Decremental PEEP titration following an ARM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient over 18 years of age&#xD;
&#xD;
          -  ICU patients with healthy lungs or lungs with Acute Respiratory Distress Syndrome&#xD;
             (according to Berlin criteria) under mechanically invasive controlled ventilation&#xD;
             (intubation or tracheotomy) in the early phase of admission (&lt; 12h)&#xD;
&#xD;
          -  Patient deeply sedated (BIS between 30 and 50) and possibly under neuromuscular&#xD;
             blocking agents (TOF &lt; 2/4 at the orbicular) in case of inspiratory efforts&#xD;
&#xD;
          -  Patient hemodynamically stable with an optimized volemia using a monitoring system&#xD;
             (see protocol).&#xD;
&#xD;
          -  Consent to participate&#xD;
&#xD;
          -  Patient benefiting from a Social Security Insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate to the proposed study&#xD;
&#xD;
          -  Obese patient with BMI ≥ 35 kg.cm-2&#xD;
&#xD;
          -  Significant hemodynamic instability defined as &gt; 20% increase in catecholamine doses&#xD;
             during the last hour, despite optimization of blood volume according to a&#xD;
             pre-established protocol&#xD;
&#xD;
          -  Contraindication to the use of the electro-impedance tomography technique&#xD;
&#xD;
               -  Thoracic lesions&#xD;
&#xD;
               -  Chest bandages&#xD;
&#xD;
               -  Pace-maker/Implantable defibrillator&#xD;
&#xD;
          -  Contraindication to the performance of an alveolar recruitment maneuver&#xD;
&#xD;
               -  Major Emphysema&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Godet</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Clermont-Ferrand</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lise Laclautre</last_name>
    <phone>+33 4 73 754963</phone>
    <email>promo_interne_drci@chu-clermontferrand.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Godet</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 24, 2021</last_update_submitted>
  <last_update_submitted_qc>August 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ICU patients</keyword>
  <keyword>Volume-controlled ventilation</keyword>
  <keyword>Open lung strategy</keyword>
  <keyword>PEEP titration</keyword>
  <keyword>Alveolar recruitment maneuver</keyword>
  <keyword>ARDS</keyword>
  <keyword>Healthy lungs</keyword>
  <keyword>Intubation</keyword>
  <keyword>Tracheotomy</keyword>
  <keyword>End-expiratory lung volume</keyword>
  <keyword>Electro-impedance tomography</keyword>
  <keyword>Recruited lung volume</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</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/NCT04503876
org study id: RBHP 2019 GODET (Peep Réa)
nct id: NCT04503876
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
PEEP titration is a recommended during invasive mechanical ventilation of ICU patients.
      However, little is known about the right way to conduct this titration. PEEP titration can be
      conducted by a stepwise increase in PEEP level, or following an ARM and a consecutive
      stepwise decrease in PEEP level. Those 2 methods will be explored in intubated ICU patients
      either with healthy lung or ARDS lungs. Physiological exploration will include end-expiratory
      lung volume measurements, driving pressure, compliance and electro-impedance tomography at
      each PEEP level.
Management of ICU patients may require the use of ventilatory support requiring tracheal
      intubation and invasive mechanical ventilation.

      Any mechanically ventilated patient is exposed to the formation of atelectasis (collapsed
      pulmonary alveoli), which occurs systematically after endotracheal tube insertion, after any
      de-recruiting action (tracheal suction, disconnection) or simply if protective ventilation is
      used, combining small tidal volumes (6 to 8 mL/kg of theoretical ideal body weight - IBW) and
      an end-expiratory positive pressure (PEEP) that is sometimes insufficient. It is thus
      proposed to perform alveolar recruitment maneuvers (ARMs), which remove atelectasis by
      temporarily increasing intrathoracic pressure. To avoid alveolar re-collapse, it is necessary
      to apply a sufficient level of PEEP.

      The opening pressure (P) necessary for the re-expansion of a collapsed alveolus is inversely
      proportional to its radius (r), following Laplace law P = 2.γ/r where γ is the surface
      tension. The pressure necessary to the re-expansion of a collapsed cell depends on its
      radius. Amato's team has showed in 2006 that within the same lung, several levels of alveolar
      aeration and thus several opening pressures coexist. The distribution of pressures was
      bimodal, with a peak around 30 cmH2O and a second around 40 cmH2O. Consequently, to allow
      complete re-expansion of atelectasis within a lung, it is necessary to apply a pressure at
      least equal to 30 cmH2O. The application of insufficient pressures cannot be expected to
      result in complete re-expansion of the lung, but rather in an increase in aeration of already
      aerated alveoli (whose radius is larger and whose opening pressure is much lower), what, in
      turn, can lead to over-distension. This is probably what can happen if the PEEP is increased
      without any previous ARM.

      The application of an ARM can also lead to an overdistension phenomenon during a reduced
      period of time (20 to 30 seconds), contrary to the direct application of a high PEEP which
      could led to an overdistension lasting a much longer period of time (possibly several hours)
      and aggravated with each administration of a tidal volume (and thus several times per
      minute). Chronic lung exposure to overdistension phenomena can induce a disintegration of
      alveolar collagen fibers (volotrauma), leading to local inflammation (biotrauma) and systemic
      inflammation by releasing pro-inflammatory molecules (cytokines...) into the bloodstream and
      led to apoptosis in distant organs (kidney, digestive tract for example).

      The optimization of mechanical ventilation requires the search for the optimal PEEP:
      insufficient, it cannot prevent atelectasis formation; too high, it would lead to alveolar
      overdistension. In current practice, the PEEP is determined arbitrary or following a stepwise
      titration, either by incremental or decremental steps. To date, scientific literature is not
      unequivocal concerning the use of ARMs and their safety. Thus, some teams prefer not to use
      ARMs and usually apply an upward PEEP level.

      The concepts presented above are valid both in patients with healthy lungs and in patients
      with "sick" lungs, the archetype and most severe form of which is acute respiratory distress
      syndrome (ARDS), which is a frequent pathology in ICU (10 to 20% of patients admitted). Its
      definition is based on the Berlin criteria published in 2012. The morality varies between 30
      and 40% depending on the severity of the respiratory impairment. Management of patients
      suffering from ARDS requires an optimization of oxygenation, which is based first of all on
      mechanical ventilation, whether invasive or not. Since the ARDS Network study published in
      2000 in the New England Journal of Medicine, it has been globally accepted that tidal volumes
      should be reduced to no more than 6 mL/kg IBW. Ventilatory management is based on concepts of
      "baby lung" and "open lung". These concepts explain that it is mandatory to consider that the
      lung volume available for mechanical ventilation is very small compared to the healthy lung
      volume (baby lung) and that the reduction in tidal volume must be accompanied by adjustments
      to keep the lung "open", combating the formation of atelectasis by the use of sufficient PEEP
      and ARMs.

      Far from this pulmonary pathology, any mechanically ventilated patient, whether in the ICU or
      operating theatre, must benefit from a protective strategy. Any inadequate adjustment of the
      ventilation parameters can lead to lung lesions induced by mechanical ventilation (VILI,
      Ventilator Induced Lung Injuries) and to lesions similar to those observed during ARDS.

      We therefore propose to explore the impact on pulmonary aeration and ventilatory parameters
      of two different strategies of PEEP optimization during invasive mechanical ventilation in
      healthy lungs and ARDS ICU patients. This randomized controlled study would allow us to
      validate our hypotheses, depending on the respiratory mechanics and patient's pulmonary
      disease.The final aim of this study is to determine the effects of a strategy based on the
      application of an ARM followed by decremental PEEP titration, compared to an incremental PEEP
      strategy without ARM, on pulmonary and ventilatory physio-(patho)-logical parameters in ICU
      patients.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Interventional trial comparing two strategies of PEEP optimization during mechanical ventilation in two groups of ICU patients: with healthy lungs or with ARDS. The study consists of comparing pulmonary pathophysiological parameters for different PEEP levels. The first strategy implies the use of an ARM followed by a stepwise decremental PEEP titration whereas the second considers a stepwise incremental PEEP titration without any previous ARM, during controlled invasive mechanical ventilation. Each patient will receive both strategies in a random consecutive order
primary purpose: Treatment
masking: Single (Participant)
masking description: Statistical analysis will be conducted by an independant statistician not involved in data collection
measure: Recruited lung volume at each PEEP level between the 2 strategies (incremental or decremental).
time frame: The last minute of each Peep Step
description: : The main endpoint is the difference between the recruited lung volume measured by nitrogen washin-washout method at the end of each PEEP level (5th minute) with the basal value measured at the beginning of the protocol, between decremental and incremental stepwise PEEP titration
measure: Homogeneity of pulmonary aeration
time frame: The last minute of each Peep Step
description: Evaluation by using the Electrical Impedance Tomography (EIT) - derived index Center of ventilation (CoV)
measure: Homogeneity of pulmonary aeration
time frame: The last minute of each Peep Step
description: Evaluation by using the Global Inhomogeneity index (GI) by electro-impedance tomography (EIT)
measure: Regional impedance variation
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of regional impedance variation (TIV: Tidal Impedance Variation) by EIT
measure: Atelectrauma
time frame: Measurement during the last minute of each PEEP step
description: Assessement of atelectrauma (RVD: Regional Ventilation Delay) by EIT
measure: Lung volume variations
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of lung volume variations by EIT (EELI : End Expiratory Lung Impedance)
measure: Mechanical power delivered Mechanical power delivered
time frame: Measurement during the last minute of each PEEP step
description: By using the formula : Power rs =RR⋅{ΔV² ⋅[1/2 ⋅ELrs +RR⋅((1+I:E) / (60⋅I:E) x Raw ]+ΔV⋅PEEP}. (Gattinoni, Intensive Care Medicine 2016)
measure: Alveolar strain
time frame: Measurement during the last minute of each PEEP step
description: Alveolar strain as assessed by TV/FRC where TV stands for tidal volume and FRC functional residual capacity.
measure: Recruited lung volume
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of recruited lung volumes (Dellamonica, Intensive Care Medicine 2011)
measure: Ventilatory dead space
time frame: Measurement during the last minute of each PEEP step
description: Ventilatory dead space = Vd/Vt. Where Vd is the dead space volume and Vt is the tidal volume
measure: Ventilatory parameters
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of the compliance = TV / (Pplat - PEEP) where TV stands for tidal volume, Pplat stands for Plateau Pressure and PEEP stands for Positive End-Expiratory Pressure
measure: Ventilatory parameters
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of the driving pressure
measure: Ventilatory parameters
time frame: Measurement during the last minute of each PEEP step
description: Evaluation of the plateau pressure
arm group label: Decremental PEEP titration following an ARM
arm group type: Active Comparator
description: PEEP will be titrated in a stepwise decremental fashion following a standardized alveolar recruitment maneuver (ARM). The ARM is a progressive increase of intra-thoracic pressure (pressure controlled mode), with a constant driving pressure of 10 cmH2O and PEEP steps (10-15-20-25-30-35 and 40 cmH2O), reaching a maximum pressure of 50 cmH2O, allowing full recruitment. PEEP steps will be conducted every 2 cmH2O (from 20 to 6 cmH2O), every 5 minutes.
arm group label: Incremental PEEP titration without any previous ARM
arm group type: Active Comparator
description: PEEP will be titrated in a stepwise incremental fashion without any previous alveolar recruitment maneuver (ARM). PEEP steps will be conducted every 2 cmH2O (from 6 to 20 cmH2O), every 5 minutes.
intervention type: Other
intervention name: Increasing PEEP setting
description: End expiratory lung volume and lung aeration measurements will be conducted using electrical impedance tomography and nitrogen washin-washout method. Measurements will be conducted during the last minute of each step.
arm group label: Incremental PEEP titration without any previous ARM
intervention type: Other
intervention name: Decreasing PEEP setting
description: End expiratory lung volume and lung aeration measurements will be conducted using electrical impedance tomography and nitrogen washin-washout method. Measurements will be conducted during the last minute of each step.
arm group label: Decremental PEEP titration following an ARM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Godet
role: Principal Investigator
affiliation: University Hospital, Clermont-Ferrand
last name: Lise Laclautre
phone: +33 4 73 754963
email: promo_interne_drci@chu-clermontferrand.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury