<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/NCT03808753</url>
  </required_header>
  <id_info>
    <org_study_id>MANEUVER_1</org_study_id>
    <nct_id>NCT03808753</nct_id>
  </id_info>
  <brief_title>Mini Fluid chAlleNge and End-expiratory Occlusion Test and to Assess flUid responsiVEness in opeRating Room</brief_title>
  <acronym>MANEUVER</acronym>
  <official_title>Mini Fluid chAlleNge and End-expiratory Occlusion Test and to Assess flUid responsiVEness in opeRating Room: 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>
  </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>
      End-expiratory occlusion test (EEOT) has been previously successfully tested in surgical&#xD;
      patients, consisting of the interruption of the mechanical ventilation for 30 seconds, and in&#xD;
      the evaluation of the changes in the SV.&#xD;
&#xD;
      The mini fluid challenge test (mFC) aims at testing the increase in SV after the rapid&#xD;
      administration of a small aliquot of the predefined FC.&#xD;
&#xD;
      Both these test have been previously evaluated in small-sized studies and never compared each&#xD;
      other.&#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 (SV) 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;
      Among these tests, the end-expiratory occlusion test (EEOT) has been previously successfully&#xD;
      tested in surgical patients, consisting of the interruption of the mechanical ventilation for&#xD;
      30 seconds, and in the evaluation of the changes in the SV. A second subgroup aims at testing&#xD;
      the increase in SV after the rapid administration of a small aliquot of the predefined FC&#xD;
      [29, 30]. This test is called mini fluid challenge (mFC). Both these test have been&#xD;
      previously evaluated in small-sized studies and never compared each other.&#xD;
&#xD;
      The primary aim of the present study is to compare the reliability of EEOT and mFC in&#xD;
      predicting fluid responsiveness in patients undergoing general surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 27, 2019</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">January 16, 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 was started during a period of intraoperative hemodynamic stability, as previously defined (i.e. change in mean arterial pressure of less than 10% during 5 minutes). The study protocol is was the following: 1) a set of measurements was 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 mFC is then performed; 4) a FC of overall 4 mL/Kg of crystalloid solution is infused over 9 minutes (T2). The attending anesthetist is allowed to interrupt the protocol at any stage for either hemodynamic instability or any other adverse effects requiring urgent treatment.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ROC curve calculation</measure>
    <time_frame>10 minutes</time_frame>
    <description>Calculation of the area under the ROC curve considering the response to the fluid challenge test (considered as gold standard).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ROC:Comparison of the areas under the ROC curve of each test (EEOT and mFC)</measure>
    <time_frame>10 minutes</time_frame>
    <description>Comparison of the areas under the ROC curve of each test (EEOT and mFC)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">103</enrollment>
  <condition>Hemodynamic Instability</condition>
  <condition>Anesthesia</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>Treatment - hemodynamic tests: EEOT and mFC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interventions: all the enrolled patients will be tested using the EEOT and the mFC.</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: EEOT and mFC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>mini fluid challenge (mFC)</intervention_name>
    <description>The mFC is performed by injecting a first aliquot of 100 ml of crystalloid over 1 minute before completing the 4 ml/kg-FC over the residual 9 minutes.</description>
    <arm_group_label>Treatment - hemodynamic tests: EEOT and mFC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All elective adults (age &gt; 18 years) consecutive patients scheduled for elective abdominal&#xD;
        surgery requiring invasive arterial monitoring and scheduled in those operating rooms&#xD;
        equipped with ventilators having an expiratory-hold function.&#xD;
&#xD;
        The preoperative exclusion criteria were 1) any recurrent cardiac arrhythmia; 2) known&#xD;
        reduced left (ejection fraction &lt; 30%) or right (systolic peak velocity of tricuspid&#xD;
        annular motion &lt; 0.17 m/s) ventricular systolic function; Body Mass Index &gt; 35; 4) chronic&#xD;
        obstructive pulmonary disease classified as GOLD ≥ 2. Once enrolled, the patient can be&#xD;
        additionally excluded because of the occurrence of one of the following intraoperative&#xD;
        conditions: 1) significant bleeding (more than 500 ml in ½ hour); 2) persistent and/or&#xD;
        recurrent extrasystoles; 3) persistent low quality of the arterial signal despite&#xD;
        optimization of the signal (see further).&#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>
    <facility>
      <name>Careggi University Hospital</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maggiore della Carità University Hospital</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Messina A, Pelaia C, Bruni A, Garofalo E, Bonicolini E, Longhini F, Dellara E, Saderi L, Romagnoli S, Sotgiu G, Cecconi M, Navalesi P. Fluid Challenge During Anesthesia: A Systematic Review and Meta-analysis. Anesth Analg. 2018 Dec;127(6):1353-1364. doi: 10.1213/ANE.0000000000003834.</citation>
    <PMID>30300177</PMID>
  </reference>
  <reference>
    <citation>Pinsky MR. Functional hemodynamic monitoring. Crit Care Clin. 2015 Jan;31(1):89-111. doi: 10.1016/j.ccc.2014.08.005.</citation>
    <PMID>25435480</PMID>
  </reference>
  <reference>
    <citation>Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRea Group. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500.</citation>
    <PMID>21792056</PMID>
  </reference>
  <reference>
    <citation>Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13.</citation>
    <PMID>25392034</PMID>
  </reference>
  <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>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>January 16, 2020</last_update_submitted>
  <last_update_submitted_qc>January 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 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>Mini Fluid Challenge</keyword>
  <keyword>End-expiratory occlusion test</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/NCT03808753
org study id: MANEUVER_1
nct id: NCT03808753
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
End-expiratory occlusion test (EEOT) has been previously successfully tested in surgical
      patients, consisting of the interruption of the mechanical ventilation for 30 seconds, and in
      the evaluation of the changes in the SV.

      The mini fluid challenge test (mFC) aims at testing the increase in SV after the rapid
      administration of a small aliquot of the predefined FC.

      Both these test have been previously evaluated in small-sized studies and never compared each
      other.
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 (SV) 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].
      Among these tests, the end-expiratory occlusion test (EEOT) has been previously successfully
      tested in surgical patients, consisting of the interruption of the mechanical ventilation for
      30 seconds, and in the evaluation of the changes in the SV. A second subgroup aims at testing
      the increase in SV after the rapid administration of a small aliquot of the predefined FC
      [29, 30]. This test is called mini fluid challenge (mFC). Both these test have been
      previously evaluated in small-sized studies and never compared each other.

      The primary aim of the present study is to compare the reliability of EEOT and mFC in
      predicting fluid responsiveness in patients undergoing general surgery.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study protocol was started during a period of intraoperative hemodynamic stability, as previously defined (i.e. change in mean arterial pressure of less than 10% during 5 minutes). The study protocol is was the following: 1) a set of measurements was 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 mFC is then performed; 4) a FC of overall 4 mL/Kg of crystalloid solution is infused over 9 minutes (T2). The attending anesthetist is allowed to interrupt the protocol at any stage for either hemodynamic instability or any other adverse effects requiring urgent treatment.
primary purpose: Diagnostic
masking: None (Open Label)
measure: ROC curve calculation
time frame: 10 minutes
description: Calculation of the area under the ROC curve considering the response to the fluid challenge test (considered as gold standard).
measure: ROC:Comparison of the areas under the ROC curve of each test (EEOT and mFC)
time frame: 10 minutes
description: Comparison of the areas under the ROC curve of each test (EEOT and mFC)
arm group label: Treatment - hemodynamic tests: EEOT and mFC
arm group type: Experimental
description: Interventions: all the enrolled patients will be tested using the EEOT and the mFC.
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: EEOT and mFC
intervention type: Other
intervention name: mini fluid challenge (mFC)
description: The mFC is performed by injecting a first aliquot of 100 ml of crystalloid over 1 minute before completing the 4 ml/kg-FC over the residual 9 minutes.
arm group label: Treatment - hemodynamic tests: EEOT and mFC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Italy
citation: Messina A, Pelaia C, Bruni A, Garofalo E, Bonicolini E, Longhini F, Dellara E, Saderi L, Romagnoli S, Sotgiu G, Cecconi M, Navalesi P. Fluid Challenge During Anesthesia: A Systematic Review and Meta-analysis. Anesth Analg. 2018 Dec;127(6):1353-1364. doi: 10.1213/ANE.0000000000003834.
PMID: 30300177
citation: Pinsky MR. Functional hemodynamic monitoring. Crit Care Clin. 2015 Jan;31(1):89-111. doi: 10.1016/j.ccc.2014.08.005.
PMID: 25435480
citation: Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRea Group. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500.
PMID: 21792056
citation: Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13.
PMID: 25392034
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
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