<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/NCT03820440</url>
  </required_header>
  <id_info>
    <org_study_id>ELVIS</org_study_id>
    <nct_id>NCT03820440</nct_id>
  </id_info>
  <brief_title>End-expiratory Occlusion Test and Lung Recruitment Maneuver to Assess Fluid responsiVeness In Surgical Patients</brief_title>
  <acronym>ELVIS</acronym>
  <official_title>End-expiratory Occlusion Test and Lung Recruitment Maneuver to Assess Fluid responsiVeness In Surgical Patients: an Open-label, Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Humanitas Clinical and Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Azienda Ospedaliero Universitaria Maggiore della Carita</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Humanitas Clinical and Research Center</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>
      The functional hemodynamic test (FHT) called passive leg raising (PLR) has been successfully&#xD;
      used for assessing the fluid responsiveness in ICU patients since 2009 and its reliability&#xD;
      has been confirmed by three large meta-analyses. However, the PLR is not usually practicable&#xD;
      in the OR.&#xD;
&#xD;
      A lot of different FHTs have been proposed, as alternative to the PLR, in ICU and, more&#xD;
      recently, OR. These tests could be basically subdivided in two groups. A subgroup of FHTs is&#xD;
      based on sudden and brief variations of the mechanical ventilation to induce a change in&#xD;
      right ventricle preload and/or after load and, as consequence, of left ventricle SV. A second&#xD;
      subgroup aims at testing the increase in SV after the rapid administration of a small aliquot&#xD;
      of the predefined FC.&#xD;
&#xD;
      Among the first group, the end-expiratory occlusion test (EEOT) and the lung recruitment&#xD;
      maneuver (LRM) have been previously successfully tested in surgical patients. The EEOT&#xD;
      consists of the interruption of the mechanical ventilation for 30 seconds, whereas the LRM&#xD;
      consists in the increase in the peak inspiratory pressure up to 30 cmH20 for 30 seconds and&#xD;
      in the assessment of the changes in the SV after the maneuvers. These tests are safe and can&#xD;
      be easily applicable during the surgery to predict fluid responsiveness and optimize the&#xD;
      fluid therapy.&#xD;
&#xD;
      The primary aim of the present study is to compare the reliability of EEOT and LRM in&#xD;
      predicting fluid responsiveness in patients undergoing general surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Targeted fluid therapy has received increasing attention in the management of patients&#xD;
      showing acute circulatory failure in both intensive care unit (ICU) and operating room (OR),&#xD;
      aiming at preventing both inadequate tissue blood flow and fluid overload [1]. In fact,&#xD;
      unnecessary fluid administration can increase morbidity and mortality and length of hospital&#xD;
      stay of critically ill and surgical patients [2-10].&#xD;
&#xD;
      Since the only physiological reason to give a fluid challenge (FC) is to increase the stroke&#xD;
      volume (SV) [11-13] and this effect is obtained only in about 50% of ICU and OR patients [14,&#xD;
      15], a vast literature investigated the possibility of predict this effect before FC&#xD;
      administration, but the issue remains extremely challenging [1, 13, 16-18]. Bedside clinical&#xD;
      signs and pressure and static volumetric static variables, do not predict fluid&#xD;
      responsiveness [17]. Moreover, several physiological factors affect the reliability of the&#xD;
      ventilator-induced dynamic changes in pulse pressure and stroke volume [pulse pressure&#xD;
      variation (PPV) and stroke volume variation (SVV), respectively], and their echographic&#xD;
      surrogates, in a significant number of ICU and OR patients [19-22].&#xD;
&#xD;
      To overcome these limitations, the functional hemodynamic assessment (i.e. the assessment of&#xD;
      the dynamic interactions of hemodynamic variables in response to a defined perturbation), of&#xD;
      fluid responsiveness has gained in popularity [17, 18, 23]. A functional hemodynamic test&#xD;
      (FHT) consist in a manoeuvre determining a sudden change in cardiac function and/or heart&#xD;
      lung interaction, affecting the hemodynamics of fluid responders and non-responders to a&#xD;
      different extent [17, 18, 23].&#xD;
&#xD;
      The FHT called passive leg raising (PLR) has been successfully used for assessing the fluid&#xD;
      responsiveness in ICU patients since 2009 [24] and its reliability has been confirmed by&#xD;
      three large meta-analyses [25-27]. However, the PLR is not usually practicable in the OR.&#xD;
&#xD;
      A lot of different FHTs have been proposed, as alternative to the PLR, in ICU and, more&#xD;
      recently, OR. These tests could be basically subdivided in two groups. A subgroup of FHTs is&#xD;
      based on sudden and brief variations of the mechanical ventilation to induce a change in&#xD;
      right ventricle preload and/or after load and, as consequence, of left ventricle SV [24, 28].&#xD;
      A second subgroup aims at testing the increase in SV after the rapid administration of a&#xD;
      small aliquot of the predefined FC [29, 30].&#xD;
&#xD;
      Among the first group, the end-expiratory occlusion test (EEOT) and the lung recruitment&#xD;
      maneuver (LRM) have been previously successfully tested in surgical patients [31-33]. The&#xD;
      EEOT consists of the interruption of the mechanical ventilation for 30 seconds, whereas the&#xD;
      LRM consists in the increase in the peak inspiratory pressure up to 30 cmH20 for 30 seconds&#xD;
      and in the assessment of the changes in the SV after the maneuvers. These tests are safe and&#xD;
      can be easily applicable during the surgery to predict fluid responsiveness and optimize the&#xD;
      fluid therapy.&#xD;
&#xD;
      The primary aim of the present study is to compare the reliability of EEOT and LRM in&#xD;
      predicting fluid responsiveness in patients undergoing general surgery.&#xD;
&#xD;
      (for Bibliography please refer to the original protocol)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">May 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study protocol is started during a period of intraoperative hemodynamic stability, as previously defined (change in mean arterial pressure of less than 10% during 5 minutes). The study protocol is the following: 1) a set of measurements is recorded (T0) at a baseline ventilation of 7 ml/Kg and then the EEOT is performed by using the software function, &quot;expiratory hold&quot;, to interrupt mechanical ventilation; 2) after one minute a set of measurements was recorded (T1); 3) the LRM is then performed; 4) after one minute another set of measurements is recorded (T2) and then a fluid challenge of 4 mL/Kg of crystalloid solution is infused over 10 minutes. The attending anesthetist is allowed to interrupt the protocol at any stage for either hemodynamic instability or any other adverse effects requiring urgent treatment. The sequence of application of EEOT and LRM on the same patient (EEOT_LRM or LRM_EEOT) is randomly generated.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC difference</measure>
    <time_frame>10 minutes after fluid challenge administration</time_frame>
    <description>To assess the difference in the area under (AUC) the receiving operator characteristic curve (ROC)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity and Specificity</measure>
    <time_frame>10 minutes after fluid challenge administration</time_frame>
    <description>ROC curve analysis to assess the sensitivity and specificity of EEOT and LRM in predicting fluid responsiveness.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Hemodynamic Instability</condition>
  <condition>Surgery</condition>
  <condition>Fluid Overload</condition>
  <arm_group>
    <arm_group_label>Treatment - hemodynamic tests</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment - hemodynamic tests:&#xD;
The EEOT is performed by interrupting the mechanical ventilation for 30 seconds, by using and end-expiratory hold on the ventilator.&#xD;
The LRM is performed by using a single act of mechanical ventilation in pressure-controlled mode at 30 cmH20 for 30 seconds</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>End-expiratory occlusion test (EEOT)</intervention_name>
    <description>The EEOT is performed by interrupting the mechanical ventilation for 30 seconds, by using and end-expiratory hold on the ventilator.</description>
    <arm_group_label>Treatment - hemodynamic tests</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Lung recruitment manovre (LRM)</intervention_name>
    <description>The LRM is performed by using a single act of mechanical ventilation in pressure-controlled mode at 30 cmH20 for 30 seconds</description>
    <arm_group_label>Treatment - hemodynamic tests</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients aged ≥ 18 years;&#xD;
&#xD;
          2. Scheduled for elective supine abdominal surgery and requiring invasive arterial&#xD;
             monitoring;&#xD;
&#xD;
          3. Glasgow coma scale 15 at recruitment. All the patients must be able to sign an&#xD;
             informed consent at the admission.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any recurrent cardiac arrhythmias;&#xD;
&#xD;
          2. Reduced left (ejection fraction &lt;30%) or right (systolic peak velocity of tricuspid&#xD;
             annular motion &lt;0.17 m/s) ventricular systolic function;&#xD;
&#xD;
          3. Chronic use beta-blocking agents.&#xD;
&#xD;
          4. History of pneumothorax.&#xD;
&#xD;
          5. BMI &gt; 40&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Humanitas Research Hospital</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Biais M, Larghi M, Henriot J, de Courson H, Sesay M, Nouette-Gaulain K. End-Expiratory Occlusion Test Predicts Fluid Responsiveness in Patients With Protective Ventilation in the Operating Room. Anesth Analg. 2017 Dec;125(6):1889-1895. doi: 10.1213/ANE.0000000000002322.</citation>
    <PMID>28742783</PMID>
  </results_reference>
  <results_reference>
    <citation>Biais M, Lanchon R, Sesay M, Le Gall L, Pereira B, Futier E, Nouette-Gaulain K. Changes in Stroke Volume Induced by Lung Recruitment Maneuver Predict Fluid Responsiveness in Mechanically Ventilated Patients in the Operating Room. Anesthesiology. 2017 Feb;126(2):260-267. doi: 10.1097/ALN.0000000000001459.</citation>
    <PMID>27922547</PMID>
  </results_reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Humanitas Clinical and Research Center</investigator_affiliation>
    <investigator_full_name>Antonio Messina</investigator_full_name>
    <investigator_title>ICU senior consultant</investigator_title>
  </responsible_party>
  <keyword>End-expiratory occlusion test</keyword>
  <keyword>Lung Recruitment Manovre</keyword>
  <keyword>Fluid responsiveness</keyword>
  <keyword>Functional Hemodynamic Test</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03820440
org study id: ELVIS
nct id: NCT03820440
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The functional hemodynamic test (FHT) called passive leg raising (PLR) has been successfully
      used for assessing the fluid responsiveness in ICU patients since 2009 and its reliability
      has been confirmed by three large meta-analyses. However, the PLR is not usually practicable
      in the OR.

      A lot of different FHTs have been proposed, as alternative to the PLR, in ICU and, more
      recently, OR. These tests could be basically subdivided in two groups. A subgroup of FHTs is
      based on sudden and brief variations of the mechanical ventilation to induce a change in
      right ventricle preload and/or after load and, as consequence, of left ventricle SV. A second
      subgroup aims at testing the increase in SV after the rapid administration of a small aliquot
      of the predefined FC.

      Among the first group, the end-expiratory occlusion test (EEOT) and the lung recruitment
      maneuver (LRM) have been previously successfully tested in surgical patients. The EEOT
      consists of the interruption of the mechanical ventilation for 30 seconds, whereas the LRM
      consists in the increase in the peak inspiratory pressure up to 30 cmH20 for 30 seconds and
      in the assessment of the changes in the SV after the maneuvers. These tests are safe and can
      be easily applicable during the surgery to predict fluid responsiveness and optimize the
      fluid therapy.

      The primary aim of the present study is to compare the reliability of EEOT and LRM in
      predicting fluid responsiveness in patients undergoing general surgery.
Targeted fluid therapy has received increasing attention in the management of patients
      showing acute circulatory failure in both intensive care unit (ICU) and operating room (OR),
      aiming at preventing both inadequate tissue blood flow and fluid overload [1]. In fact,
      unnecessary fluid administration can increase morbidity and mortality and length of hospital
      stay of critically ill and surgical patients [2-10].

      Since the only physiological reason to give a fluid challenge (FC) is to increase the stroke
      volume (SV) [11-13] and this effect is obtained only in about 50% of ICU and OR patients [14,
      15], a vast literature investigated the possibility of predict this effect before FC
      administration, but the issue remains extremely challenging [1, 13, 16-18]. Bedside clinical
      signs and pressure and static volumetric static variables, do not predict fluid
      responsiveness [17]. Moreover, several physiological factors affect the reliability of the
      ventilator-induced dynamic changes in pulse pressure and stroke volume [pulse pressure
      variation (PPV) and stroke volume variation (SVV), respectively], and their echographic
      surrogates, in a significant number of ICU and OR patients [19-22].

      To overcome these limitations, the functional hemodynamic assessment (i.e. the assessment of
      the dynamic interactions of hemodynamic variables in response to a defined perturbation), of
      fluid responsiveness has gained in popularity [17, 18, 23]. A functional hemodynamic test
      (FHT) consist in a manoeuvre determining a sudden change in cardiac function and/or heart
      lung interaction, affecting the hemodynamics of fluid responders and non-responders to a
      different extent [17, 18, 23].

      The FHT called passive leg raising (PLR) has been successfully used for assessing the fluid
      responsiveness in ICU patients since 2009 [24] and its reliability has been confirmed by
      three large meta-analyses [25-27]. However, the PLR is not usually practicable in the OR.

      A lot of different FHTs have been proposed, as alternative to the PLR, in ICU and, more
      recently, OR. These tests could be basically subdivided in two groups. A subgroup of FHTs is
      based on sudden and brief variations of the mechanical ventilation to induce a change in
      right ventricle preload and/or after load and, as consequence, of left ventricle SV [24, 28].
      A second subgroup aims at testing the increase in SV after the rapid administration of a
      small aliquot of the predefined FC [29, 30].

      Among the first group, the end-expiratory occlusion test (EEOT) and the lung recruitment
      maneuver (LRM) have been previously successfully tested in surgical patients [31-33]. The
      EEOT consists of the interruption of the mechanical ventilation for 30 seconds, whereas the
      LRM consists in the increase in the peak inspiratory pressure up to 30 cmH20 for 30 seconds
      and in the assessment of the changes in the SV after the maneuvers. These tests are safe and
      can be easily applicable during the surgery to predict fluid responsiveness and optimize the
      fluid therapy.

      The primary aim of the present study is to compare the reliability of EEOT and LRM in
      predicting fluid responsiveness in patients undergoing general surgery.

      (for Bibliography please refer to the original protocol)
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study protocol is started during a period of intraoperative hemodynamic stability, as previously defined (change in mean arterial pressure of less than 10% during 5 minutes). The study protocol is the following: 1) a set of measurements is recorded (T0) at a baseline ventilation of 7 ml/Kg and then the EEOT is performed by using the software function, "expiratory hold", to interrupt mechanical ventilation; 2) after one minute a set of measurements was recorded (T1); 3) the LRM is then performed; 4) after one minute another set of measurements is recorded (T2) and then a fluid challenge of 4 mL/Kg of crystalloid solution is infused over 10 minutes. The attending anesthetist is allowed to interrupt the protocol at any stage for either hemodynamic instability or any other adverse effects requiring urgent treatment. The sequence of application of EEOT and LRM on the same patient (EEOT_LRM or LRM_EEOT) is randomly generated.
primary purpose: Diagnostic
masking: None (Open Label)
measure: AUC difference
time frame: 10 minutes after fluid challenge administration
description: To assess the difference in the area under (AUC) the receiving operator characteristic curve (ROC)
measure: Sensitivity and Specificity
time frame: 10 minutes after fluid challenge administration
description: ROC curve analysis to assess the sensitivity and specificity of EEOT and LRM in predicting fluid responsiveness.
arm group label: Treatment - hemodynamic tests
arm group type: Experimental
description: Treatment - hemodynamic tests:
The EEOT is performed by interrupting the mechanical ventilation for 30 seconds, by using and end-expiratory hold on the ventilator.
The LRM is performed by using a single act of mechanical ventilation in pressure-controlled mode at 30 cmH20 for 30 seconds
intervention type: Diagnostic Test
intervention name: End-expiratory occlusion test (EEOT)
description: The EEOT is performed by interrupting the mechanical ventilation for 30 seconds, by using and end-expiratory hold on the ventilator.
arm group label: Treatment - hemodynamic tests
intervention type: Diagnostic Test
intervention name: Lung recruitment manovre (LRM)
description: The LRM is performed by using a single act of mechanical ventilation in pressure-controlled mode at 30 cmH20 for 30 seconds
arm group label: Treatment - hemodynamic tests
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
citation: Biais M, Larghi M, Henriot J, de Courson H, Sesay M, Nouette-Gaulain K. End-Expiratory Occlusion Test Predicts Fluid Responsiveness in Patients With Protective Ventilation in the Operating Room. Anesth Analg. 2017 Dec;125(6):1889-1895. doi: 10.1213/ANE.0000000000002322.
PMID: 28742783
citation: Biais M, Lanchon R, Sesay M, Le Gall L, Pereira B, Futier E, Nouette-Gaulain K. Changes in Stroke Volume Induced by Lung Recruitment Maneuver Predict Fluid Responsiveness in Mechanically Ventilated Patients in the Operating Room. Anesthesiology. 2017 Feb;126(2):260-267. doi: 10.1097/ALN.0000000000001459.
PMID: 27922547
responsible party type: Principal Investigator
investigator affiliation: Humanitas Clinical and Research Center
investigator full name: Antonio Messina
investigator title: ICU senior consultant
sharing ipd: Undecided