xml: <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/NCT05991258</url>
    </required_header>
    <id_info>
      <org_study_id>5607/AO/22</org_study_id>
      <nct_id>NCT05991258</nct_id>
    </id_info>
    <brief_title>Effect of End-inspiratory Airway Pressure Measurements on the Risk of VILI in Ventilated Patients</brief_title>
    <acronym>P1P2Decay</acronym>
    <official_title>Effect of Different Measurements of End-inspiratory Airway Pressure on Driving Pressure and Mechanical Power in Mechanically Ventilated Patients: the P1-P2 Decay Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Padova</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Padova</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>
        Mechanical ventilation may be associated with ventilator-induced lung injury (VILI). Several&#xD;
        respiratory variables have been employed to estimate the risk of VILI, such as tidal volumes,&#xD;
        plateau pressure, driving pressure, and mechanical power. This dissipation of energy during&#xD;
        ventilation can contribute to VILI through two mechanisms, stress relaxation and pendelluft,&#xD;
        which can be estimated at the bedside by applying an end-inspiratory pause and evaluating the&#xD;
        slow decrease in airway pressure going from the pressure corresponding to zero flow (called&#xD;
        pressure P1) and the final pressure at the end of the pause (called plateau pressure P2).&#xD;
  &#xD;
        The choice of measuring the end-inspiratory airway pressure (PawEND-INSP) at a fixed,&#xD;
        although relatively early, timepoint, i.e., after 0.5 second from the beginning of the pause,&#xD;
        as prescribed by the indications of the Acute Respiratory Distress Syndrome (ARDS) Network,&#xD;
        while assessing the risk of VILI associated with the elastic pressure of the respiratory&#xD;
        system, may not reflect the harmful potential associated with the viscoelastic properties of&#xD;
        the respiratory system. It is still unclear whether an PawEND-INSP measured at the exact&#xD;
        moment of zero flow (P1) is more reliable in the calculation of those variables, such as ΔP&#xD;
        and MP, associated with the outcomes of patients with and without ARDS, as compared to the&#xD;
        pressure measured at the end of the end-inspiratory pause (plateau pressure P2).&#xD;
  &#xD;
        This multicenter prospective observational study aims to evaluate whether the use of P1, as&#xD;
        compared to P2, affects the calculation of ΔP and MP. The secondary objectives are: 1) verify&#xD;
        whether in patients with a lung parenchyma characterized by greater parenchymal&#xD;
        heterogeneity, as assessed by EIT, P1-P2 decay is greater than in patients with greater&#xD;
        parenchymal homogeneity; 2) evaluate whether patients with both ΔP values calculated using P1&#xD;
        and P2 &lt;15 cmH2O (or both MP values calculated using P1 and P2 &lt;17 J/min) develop shorter&#xD;
        duration of invasive mechanical ventilation, shorter ICU and hospital length of stay and&#xD;
        lower ICU and hospital mortality, as compared to patients with only ΔP calculated with P1 ≥&#xD;
        15 cmH2O (or only MP calculated with P1 ≥ 17 J/min) and patients with both ΔP values&#xD;
        calculated using P1 and P2 ≥ 15 cmH2O (or both MP values calculated using P1 and P2 ≥ 17&#xD;
        J/min).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Introduction&#xD;
  &#xD;
        Mechanical ventilation is necessary to ensure survival in critically ill patients but may be&#xD;
        associated with ventilator-induced lung injury (VILI). Several respiratory variables have&#xD;
        been employed to estimate the risk of VILI:&#xD;
  &#xD;
          -  In patients with the acute respiratory distress syndrome (ARDS), the prevention of VILI&#xD;
             by limiting ventilatory pressures and volumes (i.e., tidal volumes of 4-8 mL per&#xD;
             kilogram of ideal body weight and plateau pressure [Pplat], i.e., the pressure measured&#xD;
             in the respiratory system during an end-inspiration pause of 0.5 second in the absence&#xD;
             of flow and correlated to the end-inspiratory alveolar damage, less than 30 cmH2O) has&#xD;
             been shown to improve patient survival. These ventilation settings are surrogates, yet&#xD;
             not ideal predictors, of the risk of volutrauma and barotrauma, respectively.&#xD;
  &#xD;
          -  More recently, an important role in the pathogenesis of VILI has been attributed to the&#xD;
             difference between Pplat and total positive end-expiratory pressure (PEEP), the latter&#xD;
             measured after an end-expiratory pause. This difference, known as driving pressure (ΔP),&#xD;
             represents the change in pressure above PEEP required to obtain the tidal volume in a&#xD;
             patient without spontaneous inspiratory efforts and aggregate information about&#xD;
             volutrauma, barotrauma, and atelectrauma in a single variable that is easily measurable&#xD;
             at the bedside. The increase in ΔP has been associated with worse outcomes in patients&#xD;
             with and without ARDS. Some observational studies have identified the ΔP value of 15&#xD;
             cmH2O as the threshold beyond which the risk of mortality in patients with ARDS&#xD;
             increases significantly, but others have shown that a safety threshold value for ΔP&#xD;
             cannot be identified, thus suggesting that the lower the ΔP, the lower the risk of&#xD;
             mortality.&#xD;
  &#xD;
          -  Some studies suggest that inspiratory flow and strain rate may contribute to VILI in&#xD;
             experimental animals and patients with moderate-to-severe ARDS. Therefore, taking into&#xD;
             account inspiratory flow may give more insight into the risk of VILI in mechanically&#xD;
             ventilated patients. Mechanical power (MP) is the total energy transferred from the&#xD;
             ventilator to the lungs during inspiration and includes variables such as inspiratory&#xD;
             flow and respiratory rate. MP has been shown to predict mortality in patients with and&#xD;
             without ARDS.&#xD;
  &#xD;
          -  During ventilation, the lung has a viscoelastic mechanical behavior, dissipating energy&#xD;
             both during inspiration and during expiration. This dissipation of energy can contribute&#xD;
             to VILI through two mechanisms: stress relaxation, i.e., the release of the parenchymal&#xD;
             tension accumulated during inspiration, and pendelluft, i.e., the redistribution of the&#xD;
             volume of ventilation to the alveoli with a longer time constant.&#xD;
  &#xD;
        In patients with ARDS, the lung parenchyma is heterogeneous because of the coexistence of&#xD;
        aerated alveolar units and other regions that are filled with edema or collapsed due to the&#xD;
        superimposed pressure. Therefore, both the alveolar units with shorter time constants and&#xD;
        those with longer time constants are at risk of VILI: the former are affected by higher&#xD;
        transpulmonary pressures, while the latter are exposed to pendelluft. Even lungs of patients&#xD;
        without ARDS may be heterogeneous and thus predisposed to VILI through these mechanisms,&#xD;
        e.g., because of alveolar atelectasis or consolidation and bronchiolar obstruction. Some&#xD;
        imaging techniques available for clinical use may help assessing the degree of lung&#xD;
        parenchymal heterogeneity. Electrical impedance tomography (EIT) is a non-invasive bedside&#xD;
        technique that allows assessing the distribution of lung ventilation and perfusion by&#xD;
        recording the impedance variation to small electrical currents delivered by an electrode belt&#xD;
        wrapped around the patient's chest. This method has been shown to visualize and measure&#xD;
        pendelluft during controlled mechanical ventilation. The EIT variables used to assess lung&#xD;
        heterogeneity include the center of ventilation, i.e., the variation in the distribution of&#xD;
        ventilation according to a ventro-dorsal gradient, the global inhomogeneity index, an index&#xD;
        that estimates the heterogeneity of ventilation, and the regional ventilation delay,&#xD;
        indicating the delay in ventilation compared to global ventilation due to atelectrauma or&#xD;
        differences in the time constant of different lung areas.&#xD;
  &#xD;
        Stress relaxation and pendelluft can be estimated at the bedside by applying an&#xD;
        end-inspiratory pause. During this maneuver, the airway pressure curve exhibits two&#xD;
        subsequent phases of decrease. First, a rapid pressure drop occurs, ranging from peak airway&#xD;
        pressure to the pressure corresponding to zero flow (called pressure P1), which reflects the&#xD;
        dissipation of pressure in the conduction airways. Then, a slow decrease in airway pressure&#xD;
        follows, which goes from P1 to the final pressure at the end of the pause (called plateau&#xD;
        pressure P2). The difference between P1 and P2 (P1-P2 decay) depends on stress relaxation and&#xD;
        pendelluft and can be used as index of the time constant inequalities and viscoelastic tissue&#xD;
        properties of the respiratory system.&#xD;
  &#xD;
        The choice of measuring the end-inspiratory airway pressure (PawEND-INSP) at a fixed,&#xD;
        although relatively early, timepoint, i.e., after 0.5 second from the beginning of the pause,&#xD;
        as prescribed by the indications of the ARDS Network, while assessing the risk of VILI&#xD;
        associated with the elastic pressure of the respiratory system, may not reflect the harmful&#xD;
        potential associated with the viscoelastic properties of the respiratory system.&#xD;
  &#xD;
        Previous pilot studies discouraged the use of inspiratory pauses of less than 3 seconds not&#xD;
        to underestimate respiratory system compliance and resistance. However, a delayed measurement&#xD;
        of the PawEND-INSP could lead to neglect the contribution of pulmonary viscoelastic&#xD;
        properties and pendelluft to VILI. It is still unclear whether an PawEND-INSP measured at the&#xD;
        exact moment of zero flow (P1) is more reliable in the calculation of those variables, such&#xD;
        as ΔP and MP, associated with the outcomes of patients with and without ARDS, as compared to&#xD;
        the pressure measured at the end of the end-inspiratory pause (plateau pressure P2).&#xD;
  &#xD;
        Rationale of the study&#xD;
  &#xD;
          -  The effect of P1-P2 decay on the calculation of ΔP and MP are still unclear;&#xD;
  &#xD;
          -  The use of P1 as PawEND-INSP can allow taking into account the risk of VILI associated&#xD;
             with stress relaxation and pendelluft, potentially neglected by P2;&#xD;
  &#xD;
          -  The identification of a different effect of the use of P1 or P2 on the calculation of ΔP&#xD;
             and MP can help identifying lung protective ventilation settings in mechanically&#xD;
             ventilated patients.&#xD;
  &#xD;
        Objectives of the study&#xD;
  &#xD;
        This multicenter prospective observational study aims to evaluate whether the use of P1, as&#xD;
        compared to P2, affects the calculation of ΔP and MP. The secondary objectives are: 1) verify&#xD;
        whether in patients with a lung parenchyma characterized by greater parenchymal&#xD;
        heterogeneity, as assessed by EIT, P1-P2 decay is greater than in patients with greater&#xD;
        parenchymal homogeneity; 2) evaluate whether patients with both ΔP values calculated using P1&#xD;
        and P2 &lt;1 5 cmH2O (or both MP values calculated using P1 and P2 &lt; 17 cmH2O) develop shorter&#xD;
        duration of invasive mechanical ventilation, shorter ICU and hospital length of stay and&#xD;
        lower ICU and hospital mortality, as compared to patients with only ΔP calculated with P1 ≥&#xD;
        15 cmH2O (or only MP calculated with P1 ≥ 17 cmH2O) and patients with both ΔP values&#xD;
        calculated using P1 and P2 ≥ 15 cmH2O (or both MP values calculated using P1 and P2 ≥ 17&#xD;
        cmH2O).&#xD;
  &#xD;
        Data collection&#xD;
  &#xD;
        Data will be collected for 1 year. Demographic, anthropometric and anamnestic variables,&#xD;
        ventilation settings, respiratory mechanics, and EIT variables normally collected during&#xD;
        daily clinical practice at the involved centers will be recorded within 48 hours since ICU&#xD;
        admission. Data collection for each patient will end upon discharge from the hospital. The&#xD;
        methodology of the study involves the following phases:&#xD;
  &#xD;
          1. Measurement of the endotracheal cuff pressure with a manometer and adjustment to normal&#xD;
             values&#xD;
  &#xD;
          2. Suggested mechanical ventilation settings: switching to volume-controlled mode with 10%&#xD;
             automatic inspiratory pause, 0% (or 0 seconds) inspiratory rise time, 1:2&#xD;
             inspiratory/expiratory ratio (or ratio of inspiratory time to total respiratory cycle&#xD;
             time of 33%), tidal volume of 6 mL/kg of ideal body weight and patient with no&#xD;
             spontaneous respiratory effors. Respiratory rate, PEEP and inspired oxygen fraction are&#xD;
             set according to clinical indications.&#xD;
  &#xD;
          3. First clip recording&#xD;
  &#xD;
          4. 5-second end-inspiratory pause after one complete respiratory cycle has occurred (to&#xD;
             include one complete respiratory cycle with no pause in the clip)&#xD;
  &#xD;
          5. In the recorded clip, detection with a cursor of the following pressure values:&#xD;
  &#xD;
             5.1. Peak pressure 5.2. Ppause: Pplat automatically recorded by the ventilator with the&#xD;
             10% automatic inspiratory pause (this can be also recorded during tidal breathing) 5.3.&#xD;
             P1: after the initial brief fluctuation of the flow, P1 is read at the point of zero&#xD;
             flow at the bottom of any pressure fluctuation caused by cardiac contraction 5.4. P2: P2&#xD;
             is recorded after 5 seconds of end-inspiratory pause at the bottom of any pressure&#xD;
             fluctuation caused by cardiac contraction 5.5. P0.5s: PawEND-INSP recorded after 0.5&#xD;
             seconds during the pause at the bottom of any pressure fluctuation caused by cardiac&#xD;
             contraction 5.6. P2s: PawEND-INSP recorded after 2 seconds during the pause at the&#xD;
             bottom of any pressure fluctuation caused by cardiac contraction 5.7. P3s: PawEND-INSP&#xD;
             recorded after 3 seconds during the pause at the bottom of any pressure fluctuation&#xD;
             caused by cardiac contraction 5.8. Tidal volume at the end of the inspiratory hold to&#xD;
             check for the presence of air leaks If the flow does not reach zero and/or the pressure&#xD;
             waveform shows oscillations not attributable to cardiac contractions, but to the&#xD;
             patient's respiratory efforts, the measurement is not reliable and cannot be recorded.&#xD;
             The patient should be evaluated later on or excluded from the study.&#xD;
  &#xD;
          6. Wait for 10 respiratory cycles to be completed&#xD;
  &#xD;
          7. Second clip recording&#xD;
  &#xD;
          8. 5-second end-expiratory pause after one complete respiratory cycle has occurred (to&#xD;
             include one complete respiratory cycle with no pause in the clip)&#xD;
  &#xD;
          9. In the second recorded clip, detection with the cursor of the following pressure values:&#xD;
  &#xD;
             9.1. Increase in airway pressure from the value immediately preceding the occlusion and&#xD;
             the plateau after 5 seconds (static intrinsic PEEP) 9.2. Increase in airway pressure&#xD;
             from the end-expiratory value to the value at zero flow in the respiratory cycle without&#xD;
             expiratory pause (dynamic intrinsic PEEP) If the flow does not reach zero and/or the&#xD;
             pressure waveform shows oscillations not attributable to cardiac contractions, but to&#xD;
             the patient's respiratory efforts, the measurement is not reliable and cannot be&#xD;
             recorded. The patient should be evaluated later on or excluded from the study.&#xD;
  &#xD;
         10. Check for the presence of airway closure (in patients without respiratory efforts):&#xD;
             reduce respiratory rate to 6 breaths per minute, set inspiratory flow to 5 L/min, record&#xD;
             the first breath, and check for the presence of an inflection point in the initial part&#xD;
             of the pressure-time waveform not attributable to intrinsic PEEP. In case of airway&#xD;
             closure, record the airway opening pressure value and ΔP will be calculated as the&#xD;
             difference between PawEND-INSP and airway opening pressure (AOP).&#xD;
  &#xD;
        Data will be generated in the participating centers and recorded via web application on the&#xD;
        servers of the University of Padua using the Research Electronic Data Capture (REDCap)&#xD;
        management software developed by the Unit of Biostatistics, Epidemiology and Public Health of&#xD;
        the University of Padua, which will be disseminated at a multicenter level.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 9, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Comparison among ΔP values calculated with end-inspiratory airway pressure measured at different timepoints during a 5-s-end-inspiratory pause: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)</measure>
      <time_frame>Once per patient within 48 h from ICU admission</time_frame>
      <description>Calculation of ΔP with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Comparison among MP values calculated with end-inspiratory airway pressure measured at different timepoints during a 5-s-end-inspiratory pause: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)</measure>
      <time_frame>Within 2 days from ICU admission</time_frame>
      <description>Calculation of MP with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Comparison among end-inspiratory airway pressures measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)</measure>
      <time_frame>Within 2 days from ICU admission</time_frame>
      <description>Measurement of end-inspiratory airway pressure at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Comparison among respiratory system compliance calculated with end-inspiratory airway pressure measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)</measure>
      <time_frame>Within 2 days from ICU admission</time_frame>
      <description>Calculation of respiratory system compliance with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Comparison among airway resistance calculated with end-inspiratory airway pressure measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)</measure>
      <time_frame>Within 2 days from ICU admission</time_frame>
      <description>Calculation of airway resistance with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between EIT variables indicating lung parenchymal heterogeneity and the difference between the values of P1 and P2 and the values of ΔP (or MP) calculated with P1 and P2</measure>
      <time_frame>Within 2 days from ICU admission</time_frame>
      <description>In the subgroup of patients undergoing EIT, calculation of center of ventilation, global inhomogeneity index, regional ventilation delay, and pendelluft and correlation with P1-P2 decay and the difference between ΔP (or MP) measured with P1 and P2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between ΔP calculated with P1 and P2 and duration of invasive mechanical ventilation</measure>
      <time_frame>From date of randomization until the date of ICU discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 &lt; 15 cmH2O develop shorter duration of invasive mechanical ventilation, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between ΔP calculated with P1 and P2 and 28-day ventilation-free days</measure>
      <time_frame>Within 28 days from ICU admission</time_frame>
      <description>Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 &lt; 15 cmH2O develop more 28-day ventilation-free days, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between ΔP calculated with P1 and P2 and lengths of stay</measure>
      <time_frame>From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 &lt; 15 cmH2O develop shorter ICU and hospital length of stay, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between ΔP calculated with P1 and P2 and mortality</measure>
      <time_frame>From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 &lt; 15 cmH2O develop lower ICU and hospital mortality, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between MP calculated with P1 and P2 and duration of invasive mechanical ventilation</measure>
      <time_frame>From date of randomization until the date of ICU discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with MP values calculated using both P1 and P2 &lt; 17 J/min develop shorter duration of invasive mechanical ventilation, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between MP calculated with P1 and P2 and 28-day ventilation-free days</measure>
      <time_frame>Within 28 days from ICU admission</time_frame>
      <description>Assess whether those patients ventilated with MP values calculated using both P1 and P2 &lt; 17 J/min develop more 28-day ventilation-free days, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between MP calculated with P1 and P2 and lengths of stay</measure>
      <time_frame>From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with MP values calculated using both P1 and P2 &lt; 17 J/min develop shorter ICU and hospital length of stay, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between MP calculated with P1 and P2 and mortality</measure>
      <time_frame>From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months</time_frame>
      <description>Assess whether those patients ventilated with MP values calculated using both P1 and P2 &lt; 17 J/min develop lower ICU and hospital mortality, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min</description>
    </secondary_outcome>
    <enrollment type="Anticipated">1000</enrollment>
    <condition>Acute Respiratory Failure</condition>
    <condition>Mechanical Ventilation Complication</condition>
    <condition>Ventilator-Induced Lung Injury</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Adult patients undergoing invasive mechanical ventilation with volume-controlled&#xD;
          ventilation&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion criteria:&#xD;
  &#xD;
            -  Age greater than 18 years old&#xD;
  &#xD;
            -  Endotracheal intubation or tracheostomy&#xD;
  &#xD;
            -  Controlled mechanical ventilation&#xD;
  &#xD;
            -  Patient able to tolerate a 5-second end-inspiratory and end-expiratory pause with no&#xD;
               hemodynamic or respiratory complications and pressure-time waveforms of sufficient&#xD;
               quality for interpretation&#xD;
  &#xD;
            -  Inclusion within 48 hours since ICU admission&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
          - None (provided the inclusion criteria are satisfied)&#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>Tommaso Pettenuzzo, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institute of Anesthesiology and Intensive Care, Padua University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tommaso Pettenuzzo, MD</last_name>
      <phone>00390498213090</phone>
      <email>tommaso.pettenuzzo@aopd.veneto.it</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospital of Padua</name>
        <address>
          <city>Padua</city>
          <zip>35128</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tommaso Pettenuzzo, MD</last_name>
        <phone>00390498213090</phone>
        <email>tommaso.pettenuzzo@aopd.veneto.it</email>
      </contact>
      <investigator>
        <last_name>Paolo Navalesi, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Annalisa Boscolo, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Francesco Zarantonello, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Nicolò Sella, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Alessandro De Cassai, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Federico Geraldini, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <reference>
      <citation>Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013 Nov 28;369(22):2126-36. doi: 10.1056/NEJMra1208707. No abstract available. Erratum In: N Engl J Med. 2014 Apr 24;370(17):1668-9.</citation>
      <PMID>24283226</PMID>
    </reference>
    <reference>
      <citation>Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.</citation>
      <PMID>10793162</PMID>
    </reference>
    <reference>
      <citation>Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, Ferguson ND, Gajic O, Gattinoni L, Hess D, Mancebo J, Meade MO, McAuley DF, Pesenti A, Ranieri VM, Rubenfeld GD, Rubin E, Seckel M, Slutsky AS, Talmor D, Thompson BT, Wunsch H, Uleryk E, Brozek J, Brochard LJ; American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263. doi: 10.1164/rccm.201703-0548ST. Erratum In: Am J Respir Crit Care Med. 2017 Jun 1;195(11):1540.</citation>
      <PMID>28459336</PMID>
    </reference>
    <reference>
      <citation>Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.</citation>
      <PMID>25693014</PMID>
    </reference>
    <reference>
      <citation>Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.</citation>
      <PMID>27620287</PMID>
    </reference>
    <reference>
      <citation>Protti A, Votta E. Role of tissue viscoelasticity in the pathogenesis of ventilator-induced lung injury. In: Vincent JL, ed. Annual Update in Intensive Care and Emergency Medicine 2018. Springer International Publishing; 2018:193-204.</citation>
    </reference>
    <reference>
      <citation>Chi Y, Zhao Z, Frerichs I, Long Y, He H. Prevalence and prognosis of respiratory pendelluft phenomenon in mechanically ventilated ICU patients with acute respiratory failure: a retrospective cohort study. Ann Intensive Care. 2022 Mar 5;12(1):22. doi: 10.1186/s13613-022-00995-w.</citation>
      <PMID>35246748</PMID>
    </reference>
    <reference>
      <citation>Barberis L, Manno E, Guerin C. Effect of end-inspiratory pause duration on plateau pressure in mechanically ventilated patients. Intensive Care Med. 2003 Jan;29(1):130-4. doi: 10.1007/s00134-002-1568-z. Epub 2002 Dec 6.</citation>
      <PMID>12528034</PMID>
    </reference>
    <reference>
      <citation>Mezidi M, Yonis H, Aublanc M, Lissonde F, Louf-Durier A, Perinel S, Tapponnier R, Richard JC, Guerin C. Effect of end-inspiratory plateau pressure duration on driving pressure. Intensive Care Med. 2017 Apr;43(4):587-589. doi: 10.1007/s00134-016-4651-6. Epub 2016 Dec 20. No abstract available.</citation>
      <PMID>27999900</PMID>
    </reference>
    <reference>
      <citation>Santini A, Votta E, Protti A, Mezidi M, Guerin C. Driving airway pressure: should we use a static measure to describe a dynamic phenomenon? Intensive Care Med. 2017 Oct;43(10):1544-1545. doi: 10.1007/s00134-017-4850-9. Epub 2017 Jun 1. No abstract available.</citation>
      <PMID>28573391</PMID>
    </reference>
    <reference>
      <citation>Maltais F, Reissmann H, Navalesi P, Hernandez P, Gursahaney A, Ranieri VM, Sovilj M, Gottfried SB. Comparison of static and dynamic measurements of intrinsic PEEP in mechanically ventilated patients. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 1):1318-24. doi: 10.1164/ajrccm.150.5.7952559.</citation>
      <PMID>7952559</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Padova</investigator_affiliation>
      <investigator_full_name>Tommaso Pettenuzzo</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>acute respiratory failure</keyword>
    <keyword>ventilator-induced lung injury</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Respiratory Insufficiency</mesh_term>
      <mesh_term>Lung Injury</mesh_term>
      <mesh_term>Ventilator-Induced Lung Injury</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05991258
  org study id: 5607/AO/22
  nct id: NCT05991258
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Mechanical ventilation may be associated with ventilator-induced lung injury (VILI). Several
        respiratory variables have been employed to estimate the risk of VILI, such as tidal volumes,
        plateau pressure, driving pressure, and mechanical power. This dissipation of energy during
        ventilation can contribute to VILI through two mechanisms, stress relaxation and pendelluft,
        which can be estimated at the bedside by applying an end-inspiratory pause and evaluating the
        slow decrease in airway pressure going from the pressure corresponding to zero flow (called
        pressure P1) and the final pressure at the end of the pause (called plateau pressure P2).
  
        The choice of measuring the end-inspiratory airway pressure (PawEND-INSP) at a fixed,
        although relatively early, timepoint, i.e., after 0.5 second from the beginning of the pause,
        as prescribed by the indications of the Acute Respiratory Distress Syndrome (ARDS) Network,
        while assessing the risk of VILI associated with the elastic pressure of the respiratory
        system, may not reflect the harmful potential associated with the viscoelastic properties of
        the respiratory system. It is still unclear whether an PawEND-INSP measured at the exact
        moment of zero flow (P1) is more reliable in the calculation of those variables, such as ΔP
        and MP, associated with the outcomes of patients with and without ARDS, as compared to the
        pressure measured at the end of the end-inspiratory pause (plateau pressure P2).
  
        This multicenter prospective observational study aims to evaluate whether the use of P1, as
        compared to P2, affects the calculation of ΔP and MP. The secondary objectives are: 1) verify
        whether in patients with a lung parenchyma characterized by greater parenchymal
        heterogeneity, as assessed by EIT, P1-P2 decay is greater than in patients with greater
        parenchymal homogeneity; 2) evaluate whether patients with both ΔP values calculated using P1
        and P2 <15 cmH2O (or both MP values calculated using P1 and P2 <17 J/min) develop shorter
        duration of invasive mechanical ventilation, shorter ICU and hospital length of stay and
        lower ICU and hospital mortality, as compared to patients with only ΔP calculated with P1 ≥
        15 cmH2O (or only MP calculated with P1 ≥ 17 J/min) and patients with both ΔP values
        calculated using P1 and P2 ≥ 15 cmH2O (or both MP values calculated using P1 and P2 ≥ 17
        J/min).
  Introduction
  
        Mechanical ventilation is necessary to ensure survival in critically ill patients but may be
        associated with ventilator-induced lung injury (VILI). Several respiratory variables have
        been employed to estimate the risk of VILI:
  
          -  In patients with the acute respiratory distress syndrome (ARDS), the prevention of VILI
             by limiting ventilatory pressures and volumes (i.e., tidal volumes of 4-8 mL per
             kilogram of ideal body weight and plateau pressure [Pplat], i.e., the pressure measured
             in the respiratory system during an end-inspiration pause of 0.5 second in the absence
             of flow and correlated to the end-inspiratory alveolar damage, less than 30 cmH2O) has
             been shown to improve patient survival. These ventilation settings are surrogates, yet
             not ideal predictors, of the risk of volutrauma and barotrauma, respectively.
  
          -  More recently, an important role in the pathogenesis of VILI has been attributed to the
             difference between Pplat and total positive end-expiratory pressure (PEEP), the latter
             measured after an end-expiratory pause. This difference, known as driving pressure (ΔP),
             represents the change in pressure above PEEP required to obtain the tidal volume in a
             patient without spontaneous inspiratory efforts and aggregate information about
             volutrauma, barotrauma, and atelectrauma in a single variable that is easily measurable
             at the bedside. The increase in ΔP has been associated with worse outcomes in patients
             with and without ARDS. Some observational studies have identified the ΔP value of 15
             cmH2O as the threshold beyond which the risk of mortality in patients with ARDS
             increases significantly, but others have shown that a safety threshold value for ΔP
             cannot be identified, thus suggesting that the lower the ΔP, the lower the risk of
             mortality.
  
          -  Some studies suggest that inspiratory flow and strain rate may contribute to VILI in
             experimental animals and patients with moderate-to-severe ARDS. Therefore, taking into
             account inspiratory flow may give more insight into the risk of VILI in mechanically
             ventilated patients. Mechanical power (MP) is the total energy transferred from the
             ventilator to the lungs during inspiration and includes variables such as inspiratory
             flow and respiratory rate. MP has been shown to predict mortality in patients with and
             without ARDS.
  
          -  During ventilation, the lung has a viscoelastic mechanical behavior, dissipating energy
             both during inspiration and during expiration. This dissipation of energy can contribute
             to VILI through two mechanisms: stress relaxation, i.e., the release of the parenchymal
             tension accumulated during inspiration, and pendelluft, i.e., the redistribution of the
             volume of ventilation to the alveoli with a longer time constant.
  
        In patients with ARDS, the lung parenchyma is heterogeneous because of the coexistence of
        aerated alveolar units and other regions that are filled with edema or collapsed due to the
        superimposed pressure. Therefore, both the alveolar units with shorter time constants and
        those with longer time constants are at risk of VILI: the former are affected by higher
        transpulmonary pressures, while the latter are exposed to pendelluft. Even lungs of patients
        without ARDS may be heterogeneous and thus predisposed to VILI through these mechanisms,
        e.g., because of alveolar atelectasis or consolidation and bronchiolar obstruction. Some
        imaging techniques available for clinical use may help assessing the degree of lung
        parenchymal heterogeneity. Electrical impedance tomography (EIT) is a non-invasive bedside
        technique that allows assessing the distribution of lung ventilation and perfusion by
        recording the impedance variation to small electrical currents delivered by an electrode belt
        wrapped around the patient's chest. This method has been shown to visualize and measure
        pendelluft during controlled mechanical ventilation. The EIT variables used to assess lung
        heterogeneity include the center of ventilation, i.e., the variation in the distribution of
        ventilation according to a ventro-dorsal gradient, the global inhomogeneity index, an index
        that estimates the heterogeneity of ventilation, and the regional ventilation delay,
        indicating the delay in ventilation compared to global ventilation due to atelectrauma or
        differences in the time constant of different lung areas.
  
        Stress relaxation and pendelluft can be estimated at the bedside by applying an
        end-inspiratory pause. During this maneuver, the airway pressure curve exhibits two
        subsequent phases of decrease. First, a rapid pressure drop occurs, ranging from peak airway
        pressure to the pressure corresponding to zero flow (called pressure P1), which reflects the
        dissipation of pressure in the conduction airways. Then, a slow decrease in airway pressure
        follows, which goes from P1 to the final pressure at the end of the pause (called plateau
        pressure P2). The difference between P1 and P2 (P1-P2 decay) depends on stress relaxation and
        pendelluft and can be used as index of the time constant inequalities and viscoelastic tissue
        properties of the respiratory system.
  
        The choice of measuring the end-inspiratory airway pressure (PawEND-INSP) at a fixed,
        although relatively early, timepoint, i.e., after 0.5 second from the beginning of the pause,
        as prescribed by the indications of the ARDS Network, while assessing the risk of VILI
        associated with the elastic pressure of the respiratory system, may not reflect the harmful
        potential associated with the viscoelastic properties of the respiratory system.
  
        Previous pilot studies discouraged the use of inspiratory pauses of less than 3 seconds not
        to underestimate respiratory system compliance and resistance. However, a delayed measurement
        of the PawEND-INSP could lead to neglect the contribution of pulmonary viscoelastic
        properties and pendelluft to VILI. It is still unclear whether an PawEND-INSP measured at the
        exact moment of zero flow (P1) is more reliable in the calculation of those variables, such
        as ΔP and MP, associated with the outcomes of patients with and without ARDS, as compared to
        the pressure measured at the end of the end-inspiratory pause (plateau pressure P2).
  
        Rationale of the study
  
          -  The effect of P1-P2 decay on the calculation of ΔP and MP are still unclear;
  
          -  The use of P1 as PawEND-INSP can allow taking into account the risk of VILI associated
             with stress relaxation and pendelluft, potentially neglected by P2;
  
          -  The identification of a different effect of the use of P1 or P2 on the calculation of ΔP
             and MP can help identifying lung protective ventilation settings in mechanically
             ventilated patients.
  
        Objectives of the study
  
        This multicenter prospective observational study aims to evaluate whether the use of P1, as
        compared to P2, affects the calculation of ΔP and MP. The secondary objectives are: 1) verify
        whether in patients with a lung parenchyma characterized by greater parenchymal
        heterogeneity, as assessed by EIT, P1-P2 decay is greater than in patients with greater
        parenchymal homogeneity; 2) evaluate whether patients with both ΔP values calculated using P1
        and P2 <1 5 cmH2O (or both MP values calculated using P1 and P2 < 17 cmH2O) develop shorter
        duration of invasive mechanical ventilation, shorter ICU and hospital length of stay and
        lower ICU and hospital mortality, as compared to patients with only ΔP calculated with P1 ≥
        15 cmH2O (or only MP calculated with P1 ≥ 17 cmH2O) and patients with both ΔP values
        calculated using P1 and P2 ≥ 15 cmH2O (or both MP values calculated using P1 and P2 ≥ 17
        cmH2O).
  
        Data collection
  
        Data will be collected for 1 year. Demographic, anthropometric and anamnestic variables,
        ventilation settings, respiratory mechanics, and EIT variables normally collected during
        daily clinical practice at the involved centers will be recorded within 48 hours since ICU
        admission. Data collection for each patient will end upon discharge from the hospital. The
        methodology of the study involves the following phases:
  
          1. Measurement of the endotracheal cuff pressure with a manometer and adjustment to normal
             values
  
          2. Suggested mechanical ventilation settings: switching to volume-controlled mode with 10%
             automatic inspiratory pause, 0% (or 0 seconds) inspiratory rise time, 1:2
             inspiratory/expiratory ratio (or ratio of inspiratory time to total respiratory cycle
             time of 33%), tidal volume of 6 mL/kg of ideal body weight and patient with no
             spontaneous respiratory effors. Respiratory rate, PEEP and inspired oxygen fraction are
             set according to clinical indications.
  
          3. First clip recording
  
          4. 5-second end-inspiratory pause after one complete respiratory cycle has occurred (to
             include one complete respiratory cycle with no pause in the clip)
  
          5. In the recorded clip, detection with a cursor of the following pressure values:
  
             5.1. Peak pressure 5.2. Ppause: Pplat automatically recorded by the ventilator with the
             10% automatic inspiratory pause (this can be also recorded during tidal breathing) 5.3.
             P1: after the initial brief fluctuation of the flow, P1 is read at the point of zero
             flow at the bottom of any pressure fluctuation caused by cardiac contraction 5.4. P2: P2
             is recorded after 5 seconds of end-inspiratory pause at the bottom of any pressure
             fluctuation caused by cardiac contraction 5.5. P0.5s: PawEND-INSP recorded after 0.5
             seconds during the pause at the bottom of any pressure fluctuation caused by cardiac
             contraction 5.6. P2s: PawEND-INSP recorded after 2 seconds during the pause at the
             bottom of any pressure fluctuation caused by cardiac contraction 5.7. P3s: PawEND-INSP
             recorded after 3 seconds during the pause at the bottom of any pressure fluctuation
             caused by cardiac contraction 5.8. Tidal volume at the end of the inspiratory hold to
             check for the presence of air leaks If the flow does not reach zero and/or the pressure
             waveform shows oscillations not attributable to cardiac contractions, but to the
             patient's respiratory efforts, the measurement is not reliable and cannot be recorded.
             The patient should be evaluated later on or excluded from the study.
  
          6. Wait for 10 respiratory cycles to be completed
  
          7. Second clip recording
  
          8. 5-second end-expiratory pause after one complete respiratory cycle has occurred (to
             include one complete respiratory cycle with no pause in the clip)
  
          9. In the second recorded clip, detection with the cursor of the following pressure values:
  
             9.1. Increase in airway pressure from the value immediately preceding the occlusion and
             the plateau after 5 seconds (static intrinsic PEEP) 9.2. Increase in airway pressure
             from the end-expiratory value to the value at zero flow in the respiratory cycle without
             expiratory pause (dynamic intrinsic PEEP) If the flow does not reach zero and/or the
             pressure waveform shows oscillations not attributable to cardiac contractions, but to
             the patient's respiratory efforts, the measurement is not reliable and cannot be
             recorded. The patient should be evaluated later on or excluded from the study.
  
         10. Check for the presence of airway closure (in patients without respiratory efforts):
             reduce respiratory rate to 6 breaths per minute, set inspiratory flow to 5 L/min, record
             the first breath, and check for the presence of an inflection point in the initial part
             of the pressure-time waveform not attributable to intrinsic PEEP. In case of airway
             closure, record the airway opening pressure value and ΔP will be calculated as the
             difference between PawEND-INSP and airway opening pressure (AOP).
  
        Data will be generated in the participating centers and recorded via web application on the
        servers of the University of Padua using the Research Electronic Data Capture (REDCap)
        management software developed by the Unit of Biostatistics, Epidemiology and Public Health of
        the University of Padua, which will be disseminated at a multicenter level.
  observational model: Cohort
  time perspective: Prospective
  measure: Comparison among ΔP values calculated with end-inspiratory airway pressure measured at different timepoints during a 5-s-end-inspiratory pause: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)
  time frame: Once per patient within 48 h from ICU admission
  description: Calculation of ΔP with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values
  measure: Comparison among MP values calculated with end-inspiratory airway pressure measured at different timepoints during a 5-s-end-inspiratory pause: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)
  time frame: Within 2 days from ICU admission
  description: Calculation of MP with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values
  measure: Comparison among end-inspiratory airway pressures measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)
  time frame: Within 2 days from ICU admission
  description: Measurement of end-inspiratory airway pressure at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values
  measure: Comparison among respiratory system compliance calculated with end-inspiratory airway pressure measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)
  time frame: Within 2 days from ICU admission
  description: Calculation of respiratory system compliance with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values
  measure: Comparison among airway resistance calculated with end-inspiratory airway pressure measured at different timepoints: automatic pause of the ventilator, first point of zero flow (P1), 0.5 s, 2 s, 3 s, and 5 s (P2)
  time frame: Within 2 days from ICU admission
  description: Calculation of airway resistance with end-inspiratory airway pressure measured at different timepoints (automatic pause of the ventilator, first point of zero flow [P1], 0.5 s, 2 s, 3 s, 5 s [P2]) and comparison of the different values
  measure: Correlation between EIT variables indicating lung parenchymal heterogeneity and the difference between the values of P1 and P2 and the values of ΔP (or MP) calculated with P1 and P2
  time frame: Within 2 days from ICU admission
  description: In the subgroup of patients undergoing EIT, calculation of center of ventilation, global inhomogeneity index, regional ventilation delay, and pendelluft and correlation with P1-P2 decay and the difference between ΔP (or MP) measured with P1 and P2
  measure: Association between ΔP calculated with P1 and P2 and duration of invasive mechanical ventilation
  time frame: From date of randomization until the date of ICU discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 < 15 cmH2O develop shorter duration of invasive mechanical ventilation, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O
  measure: Association between ΔP calculated with P1 and P2 and 28-day ventilation-free days
  time frame: Within 28 days from ICU admission
  description: Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 < 15 cmH2O develop more 28-day ventilation-free days, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O
  measure: Association between ΔP calculated with P1 and P2 and lengths of stay
  time frame: From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 < 15 cmH2O develop shorter ICU and hospital length of stay, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O
  measure: Association between ΔP calculated with P1 and P2 and mortality
  time frame: From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with ΔP values calculated using both P1 and P2 < 15 cmH2O develop lower ICU and hospital mortality, as compared to patients ventilated with only ΔP calculated with P1 ≥ 15 cmH2O and patients ventilated with ΔP values calculated using both P1 and P2 ≥ 15 cmH2O
  measure: Association between MP calculated with P1 and P2 and duration of invasive mechanical ventilation
  time frame: From date of randomization until the date of ICU discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with MP values calculated using both P1 and P2 < 17 J/min develop shorter duration of invasive mechanical ventilation, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min
  measure: Association between MP calculated with P1 and P2 and 28-day ventilation-free days
  time frame: Within 28 days from ICU admission
  description: Assess whether those patients ventilated with MP values calculated using both P1 and P2 < 17 J/min develop more 28-day ventilation-free days, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min
  measure: Association between MP calculated with P1 and P2 and lengths of stay
  time frame: From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with MP values calculated using both P1 and P2 < 17 J/min develop shorter ICU and hospital length of stay, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min
  measure: Association between MP calculated with P1 and P2 and mortality
  time frame: From date of randomization until the date of ICU or hospital discharge/death assessed up to 12 months
  description: Assess whether those patients ventilated with MP values calculated using both P1 and P2 < 17 J/min develop lower ICU and hospital mortality, as compared to patients ventilated with only MP calculated with P1 ≥ 17 J/min and patients ventilated with MP values calculated using both P1 and P2 ≥ 17 J/min
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tommaso Pettenuzzo, MD
  role: Principal Investigator
  affiliation: Institute of Anesthesiology and Intensive Care, Padua University Hospital
  last name: Tommaso Pettenuzzo, MD
  phone: 00390498213090
  email: tommaso.pettenuzzo@aopd.veneto.it
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: Italy
  citation: Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013 Nov 28;369(22):2126-36. doi: 10.1056/NEJMra1208707. No abstract available. Erratum In: N Engl J Med. 2014 Apr 24;370(17):1668-9.
  PMID: 24283226
  citation: Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
  PMID: 10793162
  citation: Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, Ferguson ND, Gajic O, Gattinoni L, Hess D, Mancebo J, Meade MO, McAuley DF, Pesenti A, Ranieri VM, Rubenfeld GD, Rubin E, Seckel M, Slutsky AS, Talmor D, Thompson BT, Wunsch H, Uleryk E, Brozek J, Brochard LJ; American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263. doi: 10.1164/rccm.201703-0548ST. Erratum In: Am J Respir Crit Care Med. 2017 Jun 1;195(11):1540.
  PMID: 28459336
  citation: Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.
  PMID: 25693014
  citation: Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.
  PMID: 27620287
  citation: Protti A, Votta E. Role of tissue viscoelasticity in the pathogenesis of ventilator-induced lung injury. In: Vincent JL, ed. Annual Update in Intensive Care and Emergency Medicine 2018. Springer International Publishing; 2018:193-204.
  citation: Chi Y, Zhao Z, Frerichs I, Long Y, He H. Prevalence and prognosis of respiratory pendelluft phenomenon in mechanically ventilated ICU patients with acute respiratory failure: a retrospective cohort study. Ann Intensive Care. 2022 Mar 5;12(1):22. doi: 10.1186/s13613-022-00995-w.
  PMID: 35246748
  citation: Barberis L, Manno E, Guerin C. Effect of end-inspiratory pause duration on plateau pressure in mechanically ventilated patients. Intensive Care Med. 2003 Jan;29(1):130-4. doi: 10.1007/s00134-002-1568-z. Epub 2002 Dec 6.
  PMID: 12528034
  citation: Mezidi M, Yonis H, Aublanc M, Lissonde F, Louf-Durier A, Perinel S, Tapponnier R, Richard JC, Guerin C. Effect of end-inspiratory plateau pressure duration on driving pressure. Intensive Care Med. 2017 Apr;43(4):587-589. doi: 10.1007/s00134-016-4651-6. Epub 2016 Dec 20. No abstract available.
  PMID: 27999900
  citation: Santini A, Votta E, Protti A, Mezidi M, Guerin C. Driving airway pressure: should we use a static measure to describe a dynamic phenomenon? Intensive Care Med. 2017 Oct;43(10):1544-1545. doi: 10.1007/s00134-017-4850-9. Epub 2017 Jun 1. No abstract available.
  PMID: 28573391
  citation: Maltais F, Reissmann H, Navalesi P, Hernandez P, Gursahaney A, Ranieri VM, Sovilj M, Gottfried SB. Comparison of static and dynamic measurements of intrinsic PEEP in mechanically ventilated patients. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 1):1318-24. doi: 10.1164/ajrccm.150.5.7952559.
  PMID: 7952559
  responsible party type: Principal Investigator
  investigator affiliation: University of Padova
  investigator full name: Tommaso Pettenuzzo
  investigator title: Principal Investigator
  mesh term: Respiratory Insufficiency
  mesh term: Lung Injury
  mesh term: Ventilator-Induced Lung Injury
  sharing ipd: No