<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/NCT04470856</url>
  </required_header>
  <id_info>
    <org_study_id>1677</org_study_id>
    <nct_id>NCT04470856</nct_id>
  </id_info>
  <brief_title>Carotid Doppler and EEOT for Fluid Responsiveness Prediction</brief_title>
  <official_title>Can Carotid Artery Doppler Variations Induced by End-expiratory Occlusion Manoeuvre Predict Fluid Responsiveness in Septic Shock Patients?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fluid responsiveness prediction prior to fluid challenge administration is a topic of&#xD;
      interest, which has been extensively investigated, but remains challenging.&#xD;
&#xD;
      In clinical practice, functional hemodynamic tests (FHT) consisting of maneuvers that affect&#xD;
      cardiac function and/or heart-lung interaction, have been introduced in order to identify&#xD;
      fluid responders and non-responders without fluid challenge administration.&#xD;
&#xD;
      Changes in cardiac output induced by the Passive Leg Raising (PLR) test reliably predicted&#xD;
      the increase in cardiac output to volume expansion. New approaches have been recently&#xD;
      developed based on changes in respiratory dynamics, such as a transient increase in tidal&#xD;
      volume, or a lung recruitment maneuver or an end-expiratory occlusion (EEO) test. The EEO&#xD;
      leaded to an increase in venous return, cardiac preload and stroke volume in&#xD;
      preload-responsive patients. The authors found that an increase in cardiac output ≥ 5% during&#xD;
      a 15-s EEO reliably predicted its response to a 500-ml saline infusion.&#xD;
&#xD;
      However, in order to identify the rapid and transient increase in cardiac index during the&#xD;
      EEO, continuous and instantaneous cardiac output monitoring is necessary. Pulse contour&#xD;
      analysis methods provide a beat-to-beat estimation of cardiac output and had been used in&#xD;
      most of studies validating the EEO test.&#xD;
&#xD;
      Carotid doppler is a non-invasive, bedside, easy to use ultrasound technique that measuring&#xD;
      blood flow peak velocity (CDPV) and duration of systolic component of each cardiac cycle&#xD;
      (from the onset to dicrotic notch- Flow time - FT) allows a reliable estimation of fluid&#xD;
      status and could be an interesting alternative to track changes in SV and cardiac output.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of the present study is to investigate whether changes in systolic peak velocity (ΔV&#xD;
      peak-CA) and in flow time (ΔFT) using carotid artery Doppler during an End-Expiratory&#xD;
      Occlusion Test (EEOT) predict fluid responsiveness in patients with septic shock and lung&#xD;
      protective mechanical ventilation in ICU.&#xD;
&#xD;
      All patients will be in supine position (trunk elevated 30°), sedated, paralyzed and&#xD;
      mechanically ventilated in the volume control mode. Tidal volume will be set at 6-8 ml/kg of&#xD;
      predicted body weight.&#xD;
&#xD;
      They will be all monitored by an EV1000TM/Volume View (Edwards Lifesciences Corporation,&#xD;
      Irvine, CA 92614) for measurement of cardiac index through transpulmonary thermodilution&#xD;
      (TPTD) and pulse contour analysis. Cardiac index and the other hemodynamic parameters derived&#xD;
      from pulse contour analysis will be continuously recorded over a 20-sec period.&#xD;
&#xD;
      Phase 1 (baseline): a first set of TPTD will be performed to assess the cardiac index (CI),&#xD;
      the stroke volume index (SVI), the stroke volume variation (SVV), the systemic vascular&#xD;
      resistance index (SVRI). The mean arterial pressure (MAP), heart rate (HR), central venous&#xD;
      pressure (CVP) were also recorded. A carotid doppler was performed to measure the systolic&#xD;
      peak velocity (CDPV) and the flow time (FT) (see below).&#xD;
&#xD;
      Phase 2 (EEOT): A 20-second EEO will be than applied through a touch of ventilator for&#xD;
      measuring the total end-expiratory pressure. MAP, HR, SVI, CVP, SVRI, pulse contour-derived&#xD;
      CI were averaged during the 5 last seconds of the EEO because the maximal hemodynamic effects&#xD;
      of the occlusion were observed at this time and because the EV1000TM monitor updates the data&#xD;
      every 20 seconds. During this pause a carotid Doppler will be performed and the last 5&#xD;
      seconds will be recorded.&#xD;
&#xD;
      The effects of EEOT on cardiac index will be measured by pulse contour analysis and not by&#xD;
      TPTD because these effects must be assessed by a real-time monitoring technique. In practice,&#xD;
      the investigators will observe the continuously changing values of pulse contour&#xD;
      analysis-derived cardiac index while performing the Doppler measurements.&#xD;
&#xD;
      Phase 3 (fluid challenge): The patients then will receive a 10-minute infusion of 500 mL&#xD;
      saline or lactate ringer (7 ml/kg). A last set of hemodynamic measurements, including CI,&#xD;
      MAP, HR, SVI, CVP, SVRI, and carotid Doppler, will be recorded after fluid infusion.&#xD;
&#xD;
      As soon as the cardiac index value started to increase, the investigators will consider that&#xD;
      it had reached its maximum. At this precise time, they will freeze the image of the echograph&#xD;
      and performed the Doppler measurements on the values displayed during the previous seconds.&#xD;
      If pulse contour analysis-derived cardiac index will increase ≥ 5% during the EEOT, compared&#xD;
      to the baseline value, the patient will be consider as responder to the test.&#xD;
&#xD;
      Catecholamine's infusion, mechanical ventilation settings and bed position will be kept&#xD;
      constant during the study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">July 30, 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>Sequential Assignment</intervention_model>
    <intervention_model_description>Participants receive an 20sec-EEOT at the initial phase of the study, then they receive a fluid challenge during the second phase of the study</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fluid responsiveness</measure>
    <time_frame>during EEOT</time_frame>
    <description>Evaluation of changes in systolic peak velocity (ΔV peak-CA) and in flow time (ΔFT) using carotid artery Doppler during an end-expiratory occlusion test and after fluid-challenge (500 ml)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>septic shock patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intubated patients with septic shock receive an end-expiratory occlusion test (EEOT) and, after the test, they receive a 500 ml-fluid challenge.&#xD;
During these phases the carotid doppler changes will be recorded.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>End-expiratory occlusion test (EEOT)</intervention_name>
    <description>An occlusion manoeuvre during the end of expiration for 20 seconds</description>
    <arm_group_label>septic shock patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  sedated and mechanically ventilated patients&#xD;
&#xD;
          -  need a fluid challenge&#xD;
&#xD;
          -  hypotension defined as a systolic arterial pressure ≤90 mmHg&#xD;
&#xD;
          -  tachycardia ≥100 beats/min&#xD;
&#xD;
          -  urinary flow ≤0.5 mL/kg/min for 2 hrs&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  age&lt; 18 y old&#xD;
&#xD;
          -  significant valvular heart diseases&#xD;
&#xD;
          -  cardiac arrhythmia&#xD;
&#xD;
          -  peripheral arterial disease&#xD;
&#xD;
          -  common carotid artery stenosis greater than 50%&#xD;
&#xD;
          -  spontaneous breathing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A. Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <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>Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med. 2009 Mar;37(3):951-6. doi: 10.1097/CCM.0b013e3181968fe1.</citation>
    <PMID>19237902</PMID>
  </reference>
  <reference>
    <citation>Myatra SN, Prabu NR, Divatia JV, Monnet X, Kulkarni AP, Teboul JL. The Changes in Pulse Pressure Variation or Stroke Volume Variation After a &quot;Tidal Volume Challenge&quot; Reliably Predict Fluid Responsiveness During Low Tidal Volume Ventilation. Crit Care Med. 2017 Mar;45(3):415-421. doi: 10.1097/CCM.0000000000002183.</citation>
    <PMID>27922879</PMID>
  </reference>
  <reference>
    <citation>Blehar DJ, Glazier S, Gaspari RJ. Correlation of corrected flow time in the carotid artery with changes in intravascular volume status. J Crit Care. 2014 Aug;29(4):486-8. doi: 10.1016/j.jcrc.2014.03.025. Epub 2014 Apr 2.</citation>
    <PMID>24930363</PMID>
  </reference>
  <reference>
    <citation>Mackenzie DC, Khan NA, Blehar D, Glazier S, Chang Y, Stowell CP, Noble VE, Liteplo AS. Carotid Flow Time Changes With Volume Status in Acute Blood Loss. Ann Emerg Med. 2015 Sep;66(3):277-282.e1. doi: 10.1016/j.annemergmed.2015.04.014. Epub 2015 May 21.</citation>
    <PMID>26003002</PMID>
  </reference>
  <reference>
    <citation>Hossein-Nejad H, Mohammadinejad P, Lessan-Pezeshki M, Davarani SS, Banaie M. Carotid artery corrected flow time measurement via bedside ultrasonography in monitoring volume status. J Crit Care. 2015 Dec;30(6):1199-203. doi: 10.1016/j.jcrc.2015.08.014. Epub 2015 Aug 22.</citation>
    <PMID>26410681</PMID>
  </reference>
  <reference>
    <citation>Shokoohi H, Berry GW, Shahkolahi M, King J, King J, Salimian M, Poshtmashad A, Pourmand A. The diagnostic utility of sonographic carotid flow time in determining volume responsiveness. J Crit Care. 2017 Apr;38:231-235. doi: 10.1016/j.jcrc.2016.10.025. Epub 2016 Nov 9.</citation>
    <PMID>27987483</PMID>
  </reference>
  <reference>
    <citation>Ibarra-Estrada MA, Lopez-Pulgarin JA, Mijangos-Mendez JC, Diaz-Gomez JL, Aguirre-Avalos G. Respiratory variation in carotid peak systolic velocity predicts volume responsiveness in mechanically ventilated patients with septic shock: a prospective cohort study. Crit Ultrasound J. 2015 Dec;7(1):29. doi: 10.1186/s13089-015-0029-1. Epub 2015 Jun 26.</citation>
    <PMID>26123610</PMID>
  </reference>
  <results_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>
  </results_reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>June 28, 2021</last_update_submitted>
  <last_update_submitted_qc>June 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</investigator_affiliation>
    <investigator_full_name>D'ARRIGO SONIA</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <keyword>end-expiratory occlusion test</keyword>
  <keyword>septic shock</keyword>
  <keyword>carotid doppler</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04470856
org study id: 1677
nct id: NCT04470856
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Fluid responsiveness prediction prior to fluid challenge administration is a topic of
      interest, which has been extensively investigated, but remains challenging.

      In clinical practice, functional hemodynamic tests (FHT) consisting of maneuvers that affect
      cardiac function and/or heart-lung interaction, have been introduced in order to identify
      fluid responders and non-responders without fluid challenge administration.

      Changes in cardiac output induced by the Passive Leg Raising (PLR) test reliably predicted
      the increase in cardiac output to volume expansion. New approaches have been recently
      developed based on changes in respiratory dynamics, such as a transient increase in tidal
      volume, or a lung recruitment maneuver or an end-expiratory occlusion (EEO) test. The EEO
      leaded to an increase in venous return, cardiac preload and stroke volume in
      preload-responsive patients. The authors found that an increase in cardiac output ≥ 5% during
      a 15-s EEO reliably predicted its response to a 500-ml saline infusion.

      However, in order to identify the rapid and transient increase in cardiac index during the
      EEO, continuous and instantaneous cardiac output monitoring is necessary. Pulse contour
      analysis methods provide a beat-to-beat estimation of cardiac output and had been used in
      most of studies validating the EEO test.

      Carotid doppler is a non-invasive, bedside, easy to use ultrasound technique that measuring
      blood flow peak velocity (CDPV) and duration of systolic component of each cardiac cycle
      (from the onset to dicrotic notch- Flow time - FT) allows a reliable estimation of fluid
      status and could be an interesting alternative to track changes in SV and cardiac output.
The aim of the present study is to investigate whether changes in systolic peak velocity (ΔV
      peak-CA) and in flow time (ΔFT) using carotid artery Doppler during an End-Expiratory
      Occlusion Test (EEOT) predict fluid responsiveness in patients with septic shock and lung
      protective mechanical ventilation in ICU.

      All patients will be in supine position (trunk elevated 30°), sedated, paralyzed and
      mechanically ventilated in the volume control mode. Tidal volume will be set at 6-8 ml/kg of
      predicted body weight.

      They will be all monitored by an EV1000TM/Volume View (Edwards Lifesciences Corporation,
      Irvine, CA 92614) for measurement of cardiac index through transpulmonary thermodilution
      (TPTD) and pulse contour analysis. Cardiac index and the other hemodynamic parameters derived
      from pulse contour analysis will be continuously recorded over a 20-sec period.

      Phase 1 (baseline): a first set of TPTD will be performed to assess the cardiac index (CI),
      the stroke volume index (SVI), the stroke volume variation (SVV), the systemic vascular
      resistance index (SVRI). The mean arterial pressure (MAP), heart rate (HR), central venous
      pressure (CVP) were also recorded. A carotid doppler was performed to measure the systolic
      peak velocity (CDPV) and the flow time (FT) (see below).

      Phase 2 (EEOT): A 20-second EEO will be than applied through a touch of ventilator for
      measuring the total end-expiratory pressure. MAP, HR, SVI, CVP, SVRI, pulse contour-derived
      CI were averaged during the 5 last seconds of the EEO because the maximal hemodynamic effects
      of the occlusion were observed at this time and because the EV1000TM monitor updates the data
      every 20 seconds. During this pause a carotid Doppler will be performed and the last 5
      seconds will be recorded.

      The effects of EEOT on cardiac index will be measured by pulse contour analysis and not by
      TPTD because these effects must be assessed by a real-time monitoring technique. In practice,
      the investigators will observe the continuously changing values of pulse contour
      analysis-derived cardiac index while performing the Doppler measurements.

      Phase 3 (fluid challenge): The patients then will receive a 10-minute infusion of 500 mL
      saline or lactate ringer (7 ml/kg). A last set of hemodynamic measurements, including CI,
      MAP, HR, SVI, CVP, SVRI, and carotid Doppler, will be recorded after fluid infusion.

      As soon as the cardiac index value started to increase, the investigators will consider that
      it had reached its maximum. At this precise time, they will freeze the image of the echograph
      and performed the Doppler measurements on the values displayed during the previous seconds.
      If pulse contour analysis-derived cardiac index will increase ≥ 5% during the EEOT, compared
      to the baseline value, the patient will be consider as responder to the test.

      Catecholamine's infusion, mechanical ventilation settings and bed position will be kept
      constant during the study period.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Participants receive an 20sec-EEOT at the initial phase of the study, then they receive a fluid challenge during the second phase of the study
primary purpose: Diagnostic
masking: None (Open Label)
measure: Fluid responsiveness
time frame: during EEOT
description: Evaluation of changes in systolic peak velocity (ΔV peak-CA) and in flow time (ΔFT) using carotid artery Doppler during an end-expiratory occlusion test and after fluid-challenge (500 ml)
arm group label: septic shock patients
arm group type: Experimental
description: Intubated patients with septic shock receive an end-expiratory occlusion test (EEOT) and, after the test, they receive a 500 ml-fluid challenge.
During these phases the carotid doppler changes will be recorded.
intervention type: Diagnostic Test
intervention name: End-expiratory occlusion test (EEOT)
description: An occlusion manoeuvre during the end of expiration for 20 seconds
arm group label: septic shock patients
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
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: Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med. 2009 Mar;37(3):951-6. doi: 10.1097/CCM.0b013e3181968fe1.
PMID: 19237902
citation: Myatra SN, Prabu NR, Divatia JV, Monnet X, Kulkarni AP, Teboul JL. The Changes in Pulse Pressure Variation or Stroke Volume Variation After a "Tidal Volume Challenge" Reliably Predict Fluid Responsiveness During Low Tidal Volume Ventilation. Crit Care Med. 2017 Mar;45(3):415-421. doi: 10.1097/CCM.0000000000002183.
PMID: 27922879
citation: Blehar DJ, Glazier S, Gaspari RJ. Correlation of corrected flow time in the carotid artery with changes in intravascular volume status. J Crit Care. 2014 Aug;29(4):486-8. doi: 10.1016/j.jcrc.2014.03.025. Epub 2014 Apr 2.
PMID: 24930363
citation: Mackenzie DC, Khan NA, Blehar D, Glazier S, Chang Y, Stowell CP, Noble VE, Liteplo AS. Carotid Flow Time Changes With Volume Status in Acute Blood Loss. Ann Emerg Med. 2015 Sep;66(3):277-282.e1. doi: 10.1016/j.annemergmed.2015.04.014. Epub 2015 May 21.
PMID: 26003002
citation: Hossein-Nejad H, Mohammadinejad P, Lessan-Pezeshki M, Davarani SS, Banaie M. Carotid artery corrected flow time measurement via bedside ultrasonography in monitoring volume status. J Crit Care. 2015 Dec;30(6):1199-203. doi: 10.1016/j.jcrc.2015.08.014. Epub 2015 Aug 22.
PMID: 26410681
citation: Shokoohi H, Berry GW, Shahkolahi M, King J, King J, Salimian M, Poshtmashad A, Pourmand A. The diagnostic utility of sonographic carotid flow time in determining volume responsiveness. J Crit Care. 2017 Apr;38:231-235. doi: 10.1016/j.jcrc.2016.10.025. Epub 2016 Nov 9.
PMID: 27987483
citation: Ibarra-Estrada MA, Lopez-Pulgarin JA, Mijangos-Mendez JC, Diaz-Gomez JL, Aguirre-Avalos G. Respiratory variation in carotid peak systolic velocity predicts volume responsiveness in mechanically ventilated patients with septic shock: a prospective cohort study. Crit Ultrasound J. 2015 Dec;7(1):29. doi: 10.1186/s13089-015-0029-1. Epub 2015 Jun 26.
PMID: 26123610
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
responsible party type: Principal Investigator
investigator affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
investigator full name: D'ARRIGO SONIA
investigator title: principal investigator
mesh term: Shock, Septic
mesh term: Shock
sharing ipd: No