<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/NCT03817996</url>
  </required_header>
  <id_info>
    <org_study_id>PR(AG)409/2016</org_study_id>
    <nct_id>NCT03817996</nct_id>
  </id_info>
  <brief_title>Fluid Responsiveness in HFNC Patients</brief_title>
  <acronym>HIDRATE</acronym>
  <official_title>PletHysmographic Variation InDex to pRedict Fluid Responsiveness in Spontaneously breAThing patiEnts Treated With High Flow Nasal Cannula</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Universitari Vall d'Hebron Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Universitari Vall d'Hebron Research Institute</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 plethysmographic variation index (PVi) is a measure of the respiratory-induced variations&#xD;
      in the plethysmographic waveform. Interestingly, in mechanically ventilated patients and&#xD;
      under certain conditions, PVi may reflect fluid responsiveness (FR).&#xD;
&#xD;
      Patients treated with high flow nasal cannula (HFNC), which has been described as a useful&#xD;
      supportive therapy in spontaneously breathing patients with respiratory failure, may present&#xD;
      the same hemodynamic changes, measured by transthoracic echocardiography, as those patients&#xD;
      who are mechanically ventilated (MV). The hypothesis of the present study is that the PVi may&#xD;
      predict FR in HFNC patients and, therefore, the objective is to investigate whether the PVi&#xD;
      can predict FR in patients treated with HFNC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY BACKGROUND The plethysmographic variation index (PVi) is a measure of the&#xD;
      respiratory-induced variations in the plethysmographic waveform. Interestingly, in&#xD;
      mechanically ventilated patients and under certain conditions, PVi may reflect fluid&#xD;
      responsiveness (FR) (Loupec T Crit Care Med 2011; Sandroni C Intensive Care Med 2012).&#xD;
&#xD;
      High flow nasal cannula (HFNC) has been described as a useful supportive therapy in&#xD;
      spontaneously breathing patients with respiratory failure (Roca Crit Care 2016), by&#xD;
      increasing lung volume and generating a certain level of airway positive pressure. It has&#xD;
      been shown that patients treated with HFNC may present the same hemodynamic changes, measured&#xD;
      by transthoracic echocardiography, as those patients who are mechanically ventilated (MV)&#xD;
      (Roca J Crit Care 2013). Therefore, PVi may also be useful in HFNC patients.&#xD;
&#xD;
      HYPOTHESIS AND OBJECTIVE As the hemodynamic changes associated with HFNC use are similar to&#xD;
      those observed in MV patients, the hypothesis of the present study is that PVi may predict FR&#xD;
      in HFNC patients.&#xD;
&#xD;
      The objective is to investigate whether the PVi can predict FR in patients treated with HFNC.&#xD;
&#xD;
      METHODS&#xD;
&#xD;
        1. Subjects: Patients treated with HFNC presenting with circulatory insufficiency, in whom&#xD;
           volume expansion was planned by the attending physician. Exclusion criteria included&#xD;
           spontaneous respiratory activity, cardiac arrhythmia, known intracardiac shunt, severe&#xD;
           hypoxemia (PaO2/FIO2 &lt;60 mmHg), left ventricular ejection fraction of &lt;50%, hemodynamic&#xD;
           instability during the procedure (defined as the variation in heart rate or blood&#xD;
           pressure of &gt;10% over the 15-min period before starting the protocol) and those with&#xD;
           variations in arterial pulse pressure &lt;13%.&#xD;
&#xD;
        2. Setting: Medico-surgical intensive care unit of a university hospital&#xD;
&#xD;
        3. Design: Pilot prospective, observational study&#xD;
&#xD;
        4. Procedures:&#xD;
&#xD;
      i. At baseline, all patients will be in semirecumbent position with the head at an angle of&#xD;
      45 degrees.&#xD;
&#xD;
      ii. Measurements of CO and PVI will be performed in duplicate, before and after a fluid&#xD;
      challenge (8ml/kg of colloids in 10 minutes).&#xD;
&#xD;
      iii. Cardiac output (CO) will be estimated by averaging three consecutive measures obtained&#xD;
      with transthoracic echocardiography (Porter TR. Journal of the American Society of&#xD;
      Echocardiography 2015). The PVi will be measured using Masimo SET® pulse oximetry technology.&#xD;
      The PVi is an automatic measure of the dynamic change in the perfusion index (Pi) that occurs&#xD;
      during the respiratory cycle. The perfusion index (Pi) is the ratio of nonpulsatile to&#xD;
      pulsatile blood flow through the peripheral capillary bed.&#xD;
&#xD;
      iv. The decision to administer fluid was based on the presence of at least one clinical sign&#xD;
      of inadequate tissue perfusion. Clinical signs of inadequate tissue perfusion were suspected&#xD;
      at the bedside by observing hypotension (systolic blood pressure &lt;90 mm Hg or the need for&#xD;
      norepinephrine), oliguria (urine output &lt;0.5 mL/kg/hr), and cool, mottled extremities.&#xD;
&#xD;
      v. Total flow delivered by HFNC and dosages of vasopressive drugs will be kept unchanged&#xD;
      during the entire procedure.&#xD;
&#xD;
      vi. The HFNC device (Optiflow™ system, MR850 heated humidified RT202 delivery tubing, and&#xD;
      RT050/051 nasal cannula; Fisher &amp; Paykel Healthcare Ltd, Auckland, New Zealand) consists of a&#xD;
      low resistance nasal cannula that can deliver up to 60L/min of totally conditioned (37ºC and&#xD;
      100% of relative humidity) gas admixture. It is initiated with a minimum flow of 40L/min and&#xD;
      a fraction of inspired oxygen (FIO2) of 1. Then, FIO2 is set to maintain a pulse oximetry&#xD;
      (SpO2) above 92% and flow rate is set according to the physician's judgment.&#xD;
&#xD;
      e. Endpoints: Diagnostic accuracy of the PVi (AUROC) for correctly classifying HFNC patients&#xD;
      who would respond to fluid challenge (ΔCO &gt;15%).&#xD;
&#xD;
      f. Data analysis: Changes in hemodynamic measurements induced by fluid challenge will be&#xD;
      assessed by using the nonparametric Wilcoxon's rank sum test for paired data. Patients will&#xD;
      be divided into two groups according to changes ΔCO after fluid challenge. Those presenting a&#xD;
      ΔCO &gt;15% will be considered as responders and the others as nonresponders. Hemodynamic&#xD;
      measurements will be compared using the nonparametric Mann-Whitney test for unpaired data. To&#xD;
      assess the accuracy of the PVi for correctly classifying patients who would respond to fluid&#xD;
      challenge, receiver operating characteristic curves (ROC) will be performed and the area&#xD;
      under the curves (AUROC) will be calculated. The optimal threshold of continuous variables&#xD;
      will be chosen to maximize the sum of sensitivity and specificity. This is a pilot&#xD;
      observational study that will involve 20 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 1, 2017</start_date>
  <completion_date type="Actual">April 30, 2019</completion_date>
  <primary_completion_date type="Actual">March 30, 2019</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>Best cutoff value of the PVi to identify fluid responsiveness</measure>
    <time_frame>30 minutes</time_frame>
    <description>Best cutoff value of the PVi (defined by the Youden method) for correctly classifying HFNC patients who would respond to fluid challenge (ΔCO &gt;10%).</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">30</enrollment>
  <condition>Respiratory Insufficiency</condition>
  <condition>Shock, Septic</condition>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>HFNC + hypoperfusion + Responders</arm_group_label>
    <description>Patients treated with HFNC presenting with any sign of hypoperfusion, in whom volume expansion was planned by the attending physician.&#xD;
Clinical signs of inadequate tissue perfusion were suspected at the bedside by observing hypotension (systolic blood pressure &lt;90 mm Hg or the need for norepinephrine), oliguria (urine output &lt;0.5 mL/kg/hr), and cool, mottled extremities.&#xD;
Their CO increases &gt;15% after passive leg raising.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HFNC + hypoperfusion + Non-Responders</arm_group_label>
    <description>Same as previous but their CO do not increase &gt;15% after passive leg raising maneuver.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluid challenge</intervention_name>
    <description>250ml of saline in Responders (those who increased &gt;10% their cardiac output after a passive leg raising maneuver).</description>
    <arm_group_label>HFNC + hypoperfusion + Responders</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients treated with HFNC presenting with any sign of hypoprefusion.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients treated with HFNC presenting with circulatory insufficiency defined as the&#xD;
             presence of any of the folling signs: 1) hypotension (systolic blood pressure &lt;90 mm&#xD;
             Hg or the need for norepinephrine), 2) oliguria (urine output &lt;0.5 mL/kg/hr), and 3)&#xD;
             cool, mottled extremities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac arrhythmia&#xD;
&#xD;
          -  Known intracardiac shunt&#xD;
&#xD;
          -  Severe valvular heart disease&#xD;
&#xD;
          -  Severe hypoxemia (PaO2/FIO2 &lt;60 mmHg)&#xD;
&#xD;
          -  Left ventricular ejection fraction of &lt;50%&#xD;
&#xD;
          -  Hemodynamic instability during the procedure (defined as the variation in heart rate&#xD;
             or blood pressure of &gt;10% over the 15-min period before starting the protocol) and&#xD;
             those with variations in arterial pulse pressure &lt;13%.&#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>Oriol Roca, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Vall d'Hebron</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High flow nasal cannula</keyword>
  <keyword>Nasal high flow</keyword>
  <keyword>Plethysmographic variation index</keyword>
  <keyword>Fluid responsiveness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <!-- 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/NCT03817996
org study id: PR(AG)409/2016
nct id: NCT03817996
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The plethysmographic variation index (PVi) is a measure of the respiratory-induced variations
      in the plethysmographic waveform. Interestingly, in mechanically ventilated patients and
      under certain conditions, PVi may reflect fluid responsiveness (FR).

      Patients treated with high flow nasal cannula (HFNC), which has been described as a useful
      supportive therapy in spontaneously breathing patients with respiratory failure, may present
      the same hemodynamic changes, measured by transthoracic echocardiography, as those patients
      who are mechanically ventilated (MV). The hypothesis of the present study is that the PVi may
      predict FR in HFNC patients and, therefore, the objective is to investigate whether the PVi
      can predict FR in patients treated with HFNC.
STUDY BACKGROUND The plethysmographic variation index (PVi) is a measure of the
      respiratory-induced variations in the plethysmographic waveform. Interestingly, in
      mechanically ventilated patients and under certain conditions, PVi may reflect fluid
      responsiveness (FR) (Loupec T Crit Care Med 2011; Sandroni C Intensive Care Med 2012).

      High flow nasal cannula (HFNC) has been described as a useful supportive therapy in
      spontaneously breathing patients with respiratory failure (Roca Crit Care 2016), by
      increasing lung volume and generating a certain level of airway positive pressure. It has
      been shown that patients treated with HFNC may present the same hemodynamic changes, measured
      by transthoracic echocardiography, as those patients who are mechanically ventilated (MV)
      (Roca J Crit Care 2013). Therefore, PVi may also be useful in HFNC patients.

      HYPOTHESIS AND OBJECTIVE As the hemodynamic changes associated with HFNC use are similar to
      those observed in MV patients, the hypothesis of the present study is that PVi may predict FR
      in HFNC patients.

      The objective is to investigate whether the PVi can predict FR in patients treated with HFNC.

      METHODS

        1. Subjects: Patients treated with HFNC presenting with circulatory insufficiency, in whom
           volume expansion was planned by the attending physician. Exclusion criteria included
           spontaneous respiratory activity, cardiac arrhythmia, known intracardiac shunt, severe
           hypoxemia (PaO2/FIO2 <60 mmHg), left ventricular ejection fraction of <50%, hemodynamic
           instability during the procedure (defined as the variation in heart rate or blood
           pressure of >10% over the 15-min period before starting the protocol) and those with
           variations in arterial pulse pressure <13%.

        2. Setting: Medico-surgical intensive care unit of a university hospital

        3. Design: Pilot prospective, observational study

        4. Procedures:

      i. At baseline, all patients will be in semirecumbent position with the head at an angle of
      45 degrees.

      ii. Measurements of CO and PVI will be performed in duplicate, before and after a fluid
      challenge (8ml/kg of colloids in 10 minutes).

      iii. Cardiac output (CO) will be estimated by averaging three consecutive measures obtained
      with transthoracic echocardiography (Porter TR. Journal of the American Society of
      Echocardiography 2015). The PVi will be measured using Masimo SET® pulse oximetry technology.
      The PVi is an automatic measure of the dynamic change in the perfusion index (Pi) that occurs
      during the respiratory cycle. The perfusion index (Pi) is the ratio of nonpulsatile to
      pulsatile blood flow through the peripheral capillary bed.

      iv. The decision to administer fluid was based on the presence of at least one clinical sign
      of inadequate tissue perfusion. Clinical signs of inadequate tissue perfusion were suspected
      at the bedside by observing hypotension (systolic blood pressure <90 mm Hg or the need for
      norepinephrine), oliguria (urine output <0.5 mL/kg/hr), and cool, mottled extremities.

      v. Total flow delivered by HFNC and dosages of vasopressive drugs will be kept unchanged
      during the entire procedure.

      vi. The HFNC device (Optiflow™ system, MR850 heated humidified RT202 delivery tubing, and
      RT050/051 nasal cannula; Fisher & Paykel Healthcare Ltd, Auckland, New Zealand) consists of a
      low resistance nasal cannula that can deliver up to 60L/min of totally conditioned (37ºC and
      100% of relative humidity) gas admixture. It is initiated with a minimum flow of 40L/min and
      a fraction of inspired oxygen (FIO2) of 1. Then, FIO2 is set to maintain a pulse oximetry
      (SpO2) above 92% and flow rate is set according to the physician's judgment.

      e. Endpoints: Diagnostic accuracy of the PVi (AUROC) for correctly classifying HFNC patients
      who would respond to fluid challenge (ΔCO >15%).

      f. Data analysis: Changes in hemodynamic measurements induced by fluid challenge will be
      assessed by using the nonparametric Wilcoxon's rank sum test for paired data. Patients will
      be divided into two groups according to changes ΔCO after fluid challenge. Those presenting a
      ΔCO >15% will be considered as responders and the others as nonresponders. Hemodynamic
      measurements will be compared using the nonparametric Mann-Whitney test for unpaired data. To
      assess the accuracy of the PVi for correctly classifying patients who would respond to fluid
      challenge, receiver operating characteristic curves (ROC) will be performed and the area
      under the curves (AUROC) will be calculated. The optimal threshold of continuous variables
      will be chosen to maximize the sum of sensitivity and specificity. This is a pilot
      observational study that will involve 20 patients.
observational model: Cohort
time perspective: Prospective
measure: Best cutoff value of the PVi to identify fluid responsiveness
time frame: 30 minutes
description: Best cutoff value of the PVi (defined by the Youden method) for correctly classifying HFNC patients who would respond to fluid challenge (ΔCO >10%).
arm group label: HFNC + hypoperfusion + Responders
description: Patients treated with HFNC presenting with any sign of hypoperfusion, in whom volume expansion was planned by the attending physician.
Clinical signs of inadequate tissue perfusion were suspected at the bedside by observing hypotension (systolic blood pressure <90 mm Hg or the need for norepinephrine), oliguria (urine output <0.5 mL/kg/hr), and cool, mottled extremities.
Their CO increases >15% after passive leg raising.
arm group label: HFNC + hypoperfusion + Non-Responders
description: Same as previous but their CO do not increase >15% after passive leg raising maneuver.
intervention type: Other
intervention name: Fluid challenge
description: 250ml of saline in Responders (those who increased >10% their cardiac output after a passive leg raising maneuver).
arm group label: HFNC + hypoperfusion + Responders
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oriol Roca, MD PhD
role: Principal Investigator
affiliation: Hospital Vall d'Hebron
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Shock, Septic
mesh term: Respiratory Insufficiency