<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/NCT03300323</url>
  </required_header>
  <id_info>
    <org_study_id>17.0092</org_study_id>
    <nct_id>NCT03300323</nct_id>
  </id_info>
  <brief_title>Response to Varying the Rate of Administration of a Fluid Challenge</brief_title>
  <official_title>The Impact of Different Rates of Administration of a Fluid Challenge on the Proportion of Responders and Non-responders in the Post-operative Patient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St George's Healthcare NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St George's Healthcare NHS Trust</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>
      Administration of intravenous fluids is a key step in the management of the post-operative&#xD;
      patient. Fluid management has been identified as one area that can affect rates of&#xD;
      post-operative complications and outcomes. It is important to give the right amount of fluid,&#xD;
      enough to optimise cardiovascular function, but not so much that we flood the cells. To guide&#xD;
      this, we use a fluid challenge, administration of a small amount of fluid to test the&#xD;
      cardiovascular response. At present there is significant inter-user variability in the method&#xD;
      of administration of a fluid challenge. To ensure accuracy and reliability in assessing the&#xD;
      response to a fluid challenge, the optimal method of administration needs to be determined.&#xD;
&#xD;
      The aim of this study is to investigate the optimal rate to give a fluid challenge over.&#xD;
      Patients will be randomised to receive a fluid challenge over either 5 or 20 minutes. Both of&#xD;
      these rates are within the currently accepted range. All patients will receive a dose of&#xD;
      4ml/kg of intravenous fluid. Previous work has shown this to be the optimal dose to reliably&#xD;
      stress the system.&#xD;
&#xD;
      Measurement of the mean pressure in the cardiovascular system (mean systemic filling pressure&#xD;
      or Pmsf) during the administration of a fluid challenge will be used to assess which rate of&#xD;
      administration effectively challenges the cardiovascular system. Pmsf is measured using a&#xD;
      pneumatic tourniquet inflated for sixty seconds, above an arterial line. The invasive&#xD;
      arterial pressure is observed to then determine Pmsf. Cardiac output will also be monitored&#xD;
      during and after administration of the fluid challenge. Since the microcirculation may remain&#xD;
      impaired despite stabilisation of the macrocirculation, we will also observe this at&#xD;
      baseline, on completion of the fluid challenge, and at 5 minute intervals for 15 minutes.&#xD;
      This is observed using a handheld camera placed under the tongue.&#xD;
&#xD;
      The hypothesis is that administration of a fluid challenge at a faster rate, over 5 minutes&#xD;
      as opposed to 20 minutes, will be a more effective test of the cardiovascular response. An&#xD;
      effective fluid challenge is defined as one that causes a significant rise in mean systemic&#xD;
      filling pressure. As such, a higher proportion of responders will be seen in response to the&#xD;
      faster rate of fluid challenge. A responder is defined by an increase in cardiac output or&#xD;
      stroke volume of more than 10% from baseline in response to a fluid challenge.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">February 2018</completion_date>
  <primary_completion_date type="Anticipated">February 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response to fluid administration - SV and/or CO response</measure>
    <time_frame>35 minutes</time_frame>
    <description>A response is defined by an increase in SV and/or CO by more than 10% from the starting point of fluid administration Patients are randomised to two groups and administrated fluid at two different rates. The proportions of responders in the two groups are compared.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic response to fluid administration - mean systemic filling pressure (Pmsf)</measure>
    <time_frame>35 minutes</time_frame>
    <description>The pharmacodynamic response to fluids, in terms of maximum change and duration of change in Pmsf with different rates of fluid administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic response to fluid administration - cardiac output</measure>
    <time_frame>35 minutes</time_frame>
    <description>The pharmacodynamic response to fluids, in terms of maximum change and duration of change in CO with different rates of fluid administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic response to fluid administration - blood pressure</measure>
    <time_frame>35 minutes</time_frame>
    <description>The pharmacodynamic response to fluids, in terms of maximum change and duration of change in arterial blood pressure with different rates of fluid administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microcirculation</measure>
    <time_frame>35 minutes</time_frame>
    <description>The response seen within the microcirculation with varying the rate of administration of the fluid challenge.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Peri-operative Fluid Management</condition>
  <arm_group>
    <arm_group_label>IV Fluid challenge administration _5</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4ml/kg intravenous fluid challenge administered over 5 minutes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV Fluid challenge administration 20</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4ml/kg intravenous fluid challenge administered over 20 minutes</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>IV fluid challenge administration</intervention_name>
    <description>Administration of an intravenous fluid challenge to assess for fluid responsiveness</description>
    <arm_group_label>IV Fluid challenge administration 20</arm_group_label>
    <arm_group_label>IV Fluid challenge administration _5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective surgical patients admitted post-operatively to the General and Cardiothoracic&#xD;
             Intensive Care Unit, requiring optimization with fluid therapy, as per the current&#xD;
             clinical indications.&#xD;
&#xD;
          -  Adult patients, aged &gt;18 years, who have given informed consent to participate in the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients without capacity to consent for themselves&#xD;
&#xD;
          -  Patients requiring aggressive fluid resuscitation due to life-threatening&#xD;
             cardiovascular instability, such would not allow for period of observation for&#xD;
             stability as defined in protocol.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Possible contraindications to the use of the cardiac output monitoring device, or&#xD;
             pathology known to affect accuracy of readings, including&#xD;
&#xD;
               -  Extensive peripheral arterial occlusive disease in upper limbs&#xD;
&#xD;
               -  Postoperative valvular insufficiency&#xD;
&#xD;
               -  New onset arrhythmia&#xD;
&#xD;
               -  Cardiac assist device&#xD;
&#xD;
               -  Right ventricular failure, (formal pre-operative diagnosis)&#xD;
&#xD;
               -  Severe left ventricular failure or diastolic dysfunction&#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>Maurizio Cecconi</last_name>
    <role>Study Chair</role>
    <affiliation>St George's University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Victoria Bennett</last_name>
    <phone>02087250399</phone>
    <email>v.bennett1@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maurizio Cecconi</last_name>
  </overall_contact_backup>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>October 2, 2017</last_update_submitted>
  <last_update_submitted_qc>October 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>peri-operative</keyword>
  <keyword>fluid</keyword>
  <keyword>microcirculation</keyword>
  <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/NCT03300323
org study id: 17.0092
nct id: NCT03300323
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Administration of intravenous fluids is a key step in the management of the post-operative
      patient. Fluid management has been identified as one area that can affect rates of
      post-operative complications and outcomes. It is important to give the right amount of fluid,
      enough to optimise cardiovascular function, but not so much that we flood the cells. To guide
      this, we use a fluid challenge, administration of a small amount of fluid to test the
      cardiovascular response. At present there is significant inter-user variability in the method
      of administration of a fluid challenge. To ensure accuracy and reliability in assessing the
      response to a fluid challenge, the optimal method of administration needs to be determined.

      The aim of this study is to investigate the optimal rate to give a fluid challenge over.
      Patients will be randomised to receive a fluid challenge over either 5 or 20 minutes. Both of
      these rates are within the currently accepted range. All patients will receive a dose of
      4ml/kg of intravenous fluid. Previous work has shown this to be the optimal dose to reliably
      stress the system.

      Measurement of the mean pressure in the cardiovascular system (mean systemic filling pressure
      or Pmsf) during the administration of a fluid challenge will be used to assess which rate of
      administration effectively challenges the cardiovascular system. Pmsf is measured using a
      pneumatic tourniquet inflated for sixty seconds, above an arterial line. The invasive
      arterial pressure is observed to then determine Pmsf. Cardiac output will also be monitored
      during and after administration of the fluid challenge. Since the microcirculation may remain
      impaired despite stabilisation of the macrocirculation, we will also observe this at
      baseline, on completion of the fluid challenge, and at 5 minute intervals for 15 minutes.
      This is observed using a handheld camera placed under the tongue.

      The hypothesis is that administration of a fluid challenge at a faster rate, over 5 minutes
      as opposed to 20 minutes, will be a more effective test of the cardiovascular response. An
      effective fluid challenge is defined as one that causes a significant rise in mean systemic
      filling pressure. As such, a higher proportion of responders will be seen in response to the
      faster rate of fluid challenge. A responder is defined by an increase in cardiac output or
      stroke volume of more than 10% from baseline in response to a fluid challenge.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Clinical response to fluid administration - SV and/or CO response
time frame: 35 minutes
description: A response is defined by an increase in SV and/or CO by more than 10% from the starting point of fluid administration Patients are randomised to two groups and administrated fluid at two different rates. The proportions of responders in the two groups are compared.
measure: Pharmacodynamic response to fluid administration - mean systemic filling pressure (Pmsf)
time frame: 35 minutes
description: The pharmacodynamic response to fluids, in terms of maximum change and duration of change in Pmsf with different rates of fluid administration.
measure: Pharmacodynamic response to fluid administration - cardiac output
time frame: 35 minutes
description: The pharmacodynamic response to fluids, in terms of maximum change and duration of change in CO with different rates of fluid administration.
measure: Pharmacodynamic response to fluid administration - blood pressure
time frame: 35 minutes
description: The pharmacodynamic response to fluids, in terms of maximum change and duration of change in arterial blood pressure with different rates of fluid administration.
measure: Microcirculation
time frame: 35 minutes
description: The response seen within the microcirculation with varying the rate of administration of the fluid challenge.
arm group label: IV Fluid challenge administration _5
arm group type: Active Comparator
description: 4ml/kg intravenous fluid challenge administered over 5 minutes
arm group label: IV Fluid challenge administration 20
arm group type: Active Comparator
description: 4ml/kg intravenous fluid challenge administered over 20 minutes
intervention type: Diagnostic Test
intervention name: IV fluid challenge administration
description: Administration of an intravenous fluid challenge to assess for fluid responsiveness
arm group label: IV Fluid challenge administration 20
arm group label: IV Fluid challenge administration _5
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maurizio Cecconi
role: Study Chair
affiliation: St George's University Hospital
last name: Victoria Bennett
phone: 02087250399
email: v.bennett1@nhs.net
last name: Maurizio Cecconi
responsible party type: Sponsor
sharing ipd: No