<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/NCT03832231</url>
  </required_header>
  <id_info>
    <org_study_id>APHP180264</org_study_id>
    <secondary_id>2018-A02311-54</secondary_id>
    <nct_id>NCT03832231</nct_id>
  </id_info>
  <brief_title>Use of Transient Elastogaphy to Assess Diaphragm Function in Mechanically Ventilated Patients</brief_title>
  <acronym>Elasto-ICU</acronym>
  <official_title>Evaluation of Diaphragmatic Function in Mechanically Ventilated Patients With Transient Shear Wave Elastography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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 is a life-saving treatment that can be associated with diaphragm&#xD;
      dysfunction, a potentially deleterious acquired disability. It may be the consequence of&#xD;
      disuse - under mechanical ventilation, respiratory muscles are unloaded - or the consequence&#xD;
      of muscle overuse because of insufficient unloading. Evaluating diaphragm function is&#xD;
      therefore crucial to optimally tailor the ventilator assistance. Measurement of&#xD;
      transdiaphragmatic pressure (Pdi) is the reference method to assess diaphragm function but it&#xD;
      invasiveness hinders the generalization of its use. Previous studies have reported that&#xD;
      ultrasound can quantify diaphragm thickening and that diaphragm thickening fraction (TFdi) is&#xD;
      a good marker of diaphragm function. Since diaphragm becomes stiffer when it contracts, the&#xD;
      investigators aim at exploring whether the measurement of diaphragm stiffness by transient&#xD;
      shear wave elastography would improve the evaluation of diaphragm function with ultrasound.&#xD;
&#xD;
      Therefore, the objectives of the study are to evaluate the performance of transient shear&#xD;
      wave elastography applied to the diaphragm to estimate Pdi in mechanically ventilated&#xD;
      patients as compared to TFdi and to correlate the changes in elastography derived indices, in&#xD;
      TFdi and in Pdi into different ventilatory conditions and during a spontaneous breathing&#xD;
      trial. Pdi will be obtained using catheters positioned in patients' stomachs and esophagus&#xD;
      and diaphragm stiffness will be assessed by measuring the shear modulus of the diaphragm with&#xD;
      a dedicated ultrasound machine (Aixplorer, Ultrasonic). TFdi will be also measured as&#xD;
      previously reported. Pdi, TFdi and shear modulus will be measured at the end of each four&#xD;
      following 10 minutes-conditions: 1) baseline with initial ventilator settings (set by the&#xD;
      physician in charge of patient); 2) 25%-increase in pressure support and initial PEEP; 3)&#xD;
      25%-decrease in pressure support and initial PEEP and 4) initial level of pressure support&#xD;
      and ZEEP. Finally, the same measurements will be done at the beginning of a 30 minutes&#xD;
      spontaneous breathing trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective :&#xD;
&#xD;
      The main objective is to correlate ultrasound indices (thickness, thickening, rigidity) to&#xD;
      the measurement of transdiaphragmatic pressure in the evaluation of the diaphragmatic&#xD;
      function of patients under mechanical ventilation.&#xD;
&#xD;
      Secondary objectives are: 1. Correlate thickening of the diaphragm with Pdi, 2. Correlate&#xD;
      diaphragmatic thickening with diaphragmatic stiffness 3. Describe these correlations under&#xD;
      different levels of pressure ventilatory support, 4. Describe the evolution of diaphragmatic&#xD;
      stiffness, thickening and Pdi pressure during a ventilator liberating trial.&#xD;
&#xD;
      The primary endpoint is the measurement of Pdi. The secondary endpoints are the diaphragm&#xD;
      thickening fraction and diaphragm stiffness.&#xD;
&#xD;
      Methods :&#xD;
&#xD;
      The Pdi will be obtained by measuring the esophageal and gastric pressures through&#xD;
      nasogastric tube equipped with balloons. The position of each of the balloons will be checked&#xD;
      by displaying the esophageal and gastric pressure lines. The intragastric position will be&#xD;
      confirmed by mild abdominal compression. The oesophageal position is based on visualization&#xD;
      of cardiac artifacts on the pressure pattern and signal deflations related to inspiratory&#xD;
      movements. The signals of the esophageal and gastric pressures will be displayed continuously&#xD;
      and their resultant - transdiapragmatic pressure - will be automatically calculated in real&#xD;
      time by the software. It will also record pressure in the airways at the endotracheal tube.&#xD;
&#xD;
      Patients will be placed in half-sitting position to allow better recognition of the&#xD;
      diaphragm. Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with&#xD;
      a high resolution probe (6 MHz). The probe will be positioned at the intercostal space above&#xD;
      the tenth rib on the right axillary line and directed perpendicular to the diaphragm&#xD;
      (apposition zone). The measurements will be performed &quot;offline&quot; and the calculation of the&#xD;
      thickening fraction will be performed in blind clinical conditions.&#xD;
&#xD;
      The diaphragmatic elastography will be determined using the same ultrasound system&#xD;
      (Aixplorer®, Aix en Provence, France V9, provided with a high resolution probe (SL10-2,&#xD;
      central frequency, 6 MHz)). The anatomical approach is the same as the intercostal approach&#xD;
      described previously. After finding the diaphragm in B mode, a transition to SWE&#xD;
      (elastography) mode will be performed. Three successive measurements will be made on the same&#xD;
      region of interest, the average of the three measurements will be retained. The variation of&#xD;
      the shear modulus during the inspiratory time will also be calculated post hoc. As for&#xD;
      standard ultrasound, records analysis will be performed in blind conditions.&#xD;
&#xD;
      Pdi, ultrasound derived indices and shear wave modulus will be measured under several&#xD;
      conditions.&#xD;
&#xD;
        1. At baseline: initial ventilator settings set by the physician in charge of patient&#xD;
&#xD;
        2. 25%-increase in pressure support and initial PEEP during 10 minutes&#xD;
&#xD;
        3. 25%-decrease in pressure support and initial PEEP during 10 minutes&#xD;
&#xD;
        4. initial level of pressure support without PEEP (PEEP = 0) during 10 minutes&#xD;
&#xD;
        5. Measurement of the maximal inspiratory pressure during an inspiratory occlusion maneuver&#xD;
           lasting 20 seconds.&#xD;
&#xD;
        6. A 30 minutes Ventilator liberating trial without PEEP nor Pressure Support (CPAP=0)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 14, 2019</start_date>
  <completion_date type="Actual">July 9, 2020</completion_date>
  <primary_completion_date type="Actual">February 15, 2019</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in transdiaphragmatic pressure</measure>
    <time_frame>Through patient participation, an average of 1 day</time_frame>
    <description>Reference method to assess diaphragm function computed as the difference between esophageal pressure and gastric pressure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in diaphragm thickness and thickening as expressed by the thickening fraction (ratio of the difference between inspiratory and expiratory thickness over expiratory thickness).</measure>
    <time_frame>Through patient participation, an average of 1 day</time_frame>
    <description>Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with a high resolution probe (6 MHz), anatomical structures will be identify using B-mode. A switch to TM-mode will allow us to measure the thickening fraction. A second switch to shear wave elastography allows to identify an elastography map of the diaphragm and calculate an average of the shear wave modulus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in diaphragm stiffness</measure>
    <time_frame>Through patient participation, an average of 1 day</time_frame>
    <description>Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with a high resolution probe (6 MHz), anatomical structures will be identify using B-mode. A switch to TM-mode will allow us to measure the thickening fraction. A second switch to shear wave elastography allows to identify an elastography map of the diaphragm and calculate an average of the shear wave modulus.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Success or failure at the spontaneous breathing trial</measure>
    <time_frame>Through patient participation, an average of 1 day</time_frame>
    <description>Presence of clinical intolerance criteria according to Boles et al. ERJ 20107</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Ventilator Weaning</condition>
  <condition>Intensive Care Unit</condition>
  <arm_group>
    <arm_group_label>Ventilator liberating trial</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The diaphragmatic function of patients undergoing a ventilator liberating trial will be determined with transient shear wave elastography.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Shear Wave Elastography</intervention_name>
    <description>Ultrasound technology to assess tissue stiffness</description>
    <arm_group_label>Ventilator liberating trial</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All patients receiving mechanical ventilation and having spontaneous efforts will be&#xD;
        eligible if they meet the following criteria:&#xD;
&#xD;
        Inclusion criteria&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Intubation and mechanical ventilation since 24 hours&#xD;
&#xD;
          -  Failure to a first ventilator liberating trial&#xD;
&#xD;
          -  nasogastric feeding tube in place&#xD;
&#xD;
          -  readiness criteria to undertake a ventilator liberating trial (Boles et al. ERJ 2007)&#xD;
&#xD;
          -  patient written consent or next of kin written consent in case of physical inability&#xD;
             of the patient to sign the consent form&#xD;
&#xD;
          -  french social Health Service registration&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  protective administrative control&#xD;
&#xD;
          -  patient's refusal&#xD;
&#xD;
          -  contra indications to the insertion of esophageal and gastric balloons&#xD;
&#xD;
          -  allergy to topical anesthetic&#xD;
&#xD;
          -  impossible weaning (full dependance to mechanical ventilation)&#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>Martin DRES, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique Hoptiaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpétrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Shear wave elastography</keyword>
  <keyword>Ultrasonography</keyword>
  <keyword>Transdiaphragmatic pressure</keyword>
  <keyword>Diaphragmatic function</keyword>
  <keyword>Mechanical ventilation</keyword>
  <!-- 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/NCT03832231
org study id: APHP180264
secondary id: 2018-A02311-54
nct id: NCT03832231
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Mechanical ventilation is a life-saving treatment that can be associated with diaphragm
      dysfunction, a potentially deleterious acquired disability. It may be the consequence of
      disuse - under mechanical ventilation, respiratory muscles are unloaded - or the consequence
      of muscle overuse because of insufficient unloading. Evaluating diaphragm function is
      therefore crucial to optimally tailor the ventilator assistance. Measurement of
      transdiaphragmatic pressure (Pdi) is the reference method to assess diaphragm function but it
      invasiveness hinders the generalization of its use. Previous studies have reported that
      ultrasound can quantify diaphragm thickening and that diaphragm thickening fraction (TFdi) is
      a good marker of diaphragm function. Since diaphragm becomes stiffer when it contracts, the
      investigators aim at exploring whether the measurement of diaphragm stiffness by transient
      shear wave elastography would improve the evaluation of diaphragm function with ultrasound.

      Therefore, the objectives of the study are to evaluate the performance of transient shear
      wave elastography applied to the diaphragm to estimate Pdi in mechanically ventilated
      patients as compared to TFdi and to correlate the changes in elastography derived indices, in
      TFdi and in Pdi into different ventilatory conditions and during a spontaneous breathing
      trial. Pdi will be obtained using catheters positioned in patients' stomachs and esophagus
      and diaphragm stiffness will be assessed by measuring the shear modulus of the diaphragm with
      a dedicated ultrasound machine (Aixplorer, Ultrasonic). TFdi will be also measured as
      previously reported. Pdi, TFdi and shear modulus will be measured at the end of each four
      following 10 minutes-conditions: 1) baseline with initial ventilator settings (set by the
      physician in charge of patient); 2) 25%-increase in pressure support and initial PEEP; 3)
      25%-decrease in pressure support and initial PEEP and 4) initial level of pressure support
      and ZEEP. Finally, the same measurements will be done at the beginning of a 30 minutes
      spontaneous breathing trial.
Objective :

      The main objective is to correlate ultrasound indices (thickness, thickening, rigidity) to
      the measurement of transdiaphragmatic pressure in the evaluation of the diaphragmatic
      function of patients under mechanical ventilation.

      Secondary objectives are: 1. Correlate thickening of the diaphragm with Pdi, 2. Correlate
      diaphragmatic thickening with diaphragmatic stiffness 3. Describe these correlations under
      different levels of pressure ventilatory support, 4. Describe the evolution of diaphragmatic
      stiffness, thickening and Pdi pressure during a ventilator liberating trial.

      The primary endpoint is the measurement of Pdi. The secondary endpoints are the diaphragm
      thickening fraction and diaphragm stiffness.

      Methods :

      The Pdi will be obtained by measuring the esophageal and gastric pressures through
      nasogastric tube equipped with balloons. The position of each of the balloons will be checked
      by displaying the esophageal and gastric pressure lines. The intragastric position will be
      confirmed by mild abdominal compression. The oesophageal position is based on visualization
      of cardiac artifacts on the pressure pattern and signal deflations related to inspiratory
      movements. The signals of the esophageal and gastric pressures will be displayed continuously
      and their resultant - transdiapragmatic pressure - will be automatically calculated in real
      time by the software. It will also record pressure in the airways at the endotracheal tube.

      Patients will be placed in half-sitting position to allow better recognition of the
      diaphragm. Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with
      a high resolution probe (6 MHz). The probe will be positioned at the intercostal space above
      the tenth rib on the right axillary line and directed perpendicular to the diaphragm
      (apposition zone). The measurements will be performed "offline" and the calculation of the
      thickening fraction will be performed in blind clinical conditions.

      The diaphragmatic elastography will be determined using the same ultrasound system
      (Aixplorer®, Aix en Provence, France V9, provided with a high resolution probe (SL10-2,
      central frequency, 6 MHz)). The anatomical approach is the same as the intercostal approach
      described previously. After finding the diaphragm in B mode, a transition to SWE
      (elastography) mode will be performed. Three successive measurements will be made on the same
      region of interest, the average of the three measurements will be retained. The variation of
      the shear modulus during the inspiratory time will also be calculated post hoc. As for
      standard ultrasound, records analysis will be performed in blind conditions.

      Pdi, ultrasound derived indices and shear wave modulus will be measured under several
      conditions.

        1. At baseline: initial ventilator settings set by the physician in charge of patient

        2. 25%-increase in pressure support and initial PEEP during 10 minutes

        3. 25%-decrease in pressure support and initial PEEP during 10 minutes

        4. initial level of pressure support without PEEP (PEEP = 0) during 10 minutes

        5. Measurement of the maximal inspiratory pressure during an inspiratory occlusion maneuver
           lasting 20 seconds.

        6. A 30 minutes Ventilator liberating trial without PEEP nor Pressure Support (CPAP=0)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Change in transdiaphragmatic pressure
time frame: Through patient participation, an average of 1 day
description: Reference method to assess diaphragm function computed as the difference between esophageal pressure and gastric pressure
measure: Change in diaphragm thickness and thickening as expressed by the thickening fraction (ratio of the difference between inspiratory and expiratory thickness over expiratory thickness).
time frame: Through patient participation, an average of 1 day
description: Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with a high resolution probe (6 MHz), anatomical structures will be identify using B-mode. A switch to TM-mode will allow us to measure the thickening fraction. A second switch to shear wave elastography allows to identify an elastography map of the diaphragm and calculate an average of the shear wave modulus.
measure: Change in diaphragm stiffness
time frame: Through patient participation, an average of 1 day
description: Using the ultrasound system Aixplorer® (Aix en Provence, France V9), equipped with a high resolution probe (6 MHz), anatomical structures will be identify using B-mode. A switch to TM-mode will allow us to measure the thickening fraction. A second switch to shear wave elastography allows to identify an elastography map of the diaphragm and calculate an average of the shear wave modulus.
measure: Success or failure at the spontaneous breathing trial
time frame: Through patient participation, an average of 1 day
description: Presence of clinical intolerance criteria according to Boles et al. ERJ 20107
arm group label: Ventilator liberating trial
arm group type: Experimental
description: The diaphragmatic function of patients undergoing a ventilator liberating trial will be determined with transient shear wave elastography.
intervention type: Device
intervention name: Shear Wave Elastography
description: Ultrasound technology to assess tissue stiffness
arm group label: Ventilator liberating trial
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin DRES, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique Hoptiaux de Paris
facility: 
country: France
responsible party type: Sponsor