<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/NCT01681251</url>
  </required_header>
  <id_info>
    <org_study_id>B2009:135</org_study_id>
    <nct_id>NCT01681251</nct_id>
  </id_info>
  <brief_title>Goal Directed Therapy for Patients Undergoing Major Vascular Surgery</brief_title>
  <official_title>Goal Directed Therapy for Patients Undergoing Major Vascular Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manitoba</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The management and delivery of intravenous fluids during surgical operations is one of the&#xD;
      important duties for anesthesiologists.&#xD;
&#xD;
      The goal of this study was to determine if goal directed fluid therapy, titrated using the&#xD;
      FloTrac monitor's measurement of stroke volume variation results in a decrease in the length&#xD;
      of stay of patients undergoing open abdominal aneurysm repair.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The management and delivery of intravenous fluids during surgical operations is one of the&#xD;
      important duties for anesthesiologists. There is a growing body of evidence that fluid&#xD;
      overload in surgical patients is associated with decreased wound healing, slower return of&#xD;
      gut function, anastomotic breakdown, pulmonary edema and post-operative visual changes.&#xD;
&#xD;
      In the United States, abdominal aortic aneurysms are diagnosed in 190,000 people per year,&#xD;
      and over 50,000 of those have the aneurysm repaired5. Recent advances in endovascular&#xD;
      techniques have allowed many of these patients to forego an open repair. However, because of&#xD;
      technical difficulties, many patients still require an open repair.&#xD;
&#xD;
      The most common cause of morbidity in these patients is related to post-operative&#xD;
      gastrointestinal tract dysfunction. This usually involves an adynamic ileus that the patients&#xD;
      develop on the fourth post-operative day. This delays their tolerance of enteral foods and&#xD;
      lengthens their hospital stay and hospital costs. It also has the potential of causing more&#xD;
      morbidity in that patients may require total parenteral nutrition while awaiting return of&#xD;
      bowel function.&#xD;
&#xD;
      There are several causes of this gastrointestinal morbidity including direct mechanical&#xD;
      trauma to the bowel during surgery and activation of the inflammatory cascade. These factors&#xD;
      are unfortunately not modifiable by the team caring for the patient. One factor that is&#xD;
      modifiable is the amount and type of intravenous fluids administered to the patient.&#xD;
&#xD;
      Typically, anesthesiologists decide on the amount of fluid to administer to patients based on&#xD;
      parameters such as heart rate, blood pressure and urine output. These are unfortunately&#xD;
      unreliable in determining a patient's volume status, as these parameters can be within the&#xD;
      normal range, and a patient might still have inadequate perfusion to their vital organs.&#xD;
      Further, clinician's reliance on blood pressure as a target for fluid administration ignores&#xD;
      the fact that organs require blood flow as well as pressure to function optimally. Until&#xD;
      recently, the only way to measure blood flow was with the insertion of a pulmonary artery&#xD;
      catheter. Based on several studies showing a lack of benefit of this invasive procedure, it&#xD;
      has fallen out of favor in the non-cardiac arena. Newer monitors of cardiac output that can&#xD;
      be attached to a patients arterial catheter (commonly placed for major surgical procedures)&#xD;
      offer an alternative method for clinicians to measure cardiac output.&#xD;
&#xD;
      One of these monitors, the FloTrac system (Edwards Life Sciences, Irvine CA), utilizes the&#xD;
      arterial pulse contour to calculate cardiac output (CO) and the stroke volume variation (SVV)&#xD;
      as a monitor of volume status. In patients who are mechanically ventilated there is a phasic&#xD;
      variation in CO and stroke volume based on the ventilatory cycle. Large changes in stroke&#xD;
      volume during the ventilatory cycle may indicate hypovolemia in patients. The administration&#xD;
      of intravenous fluid to these patients results in a decrease in the SVV. Thus, the SVV can be&#xD;
      use a volume monitor and used to titrate intravenous therapy. There have been several trials&#xD;
      (mostly in colonic resection surgery) that have looked at such goal directed therapy with&#xD;
      this and similar devices and have found a decrease in patient morbidity and length of stay.&#xD;
&#xD;
      All of these studies have in common the use of a minimally invasive CO monitor and a reliance&#xD;
      on colloids as the predominant fluid utilized during the case.&#xD;
&#xD;
      The utilization of SVV to determine volume status is a novel approach to fluid management in&#xD;
      surgical patients. As stated above, clinicians' historical reliance on pressures (such as as&#xD;
      blood pressure and central venous pressure) to estimate intravascular volume status is based&#xD;
      on an incomplete understanding on the factors that govern organ blood flow. To this end, the&#xD;
      investigators will also assess several parameters during this study in an attempt to&#xD;
      ascertain which is the best at predicting fluid responsiveness. Fluid responsiveness is&#xD;
      defined as the ability to predict if a given patient will increase their CO to a fluid bolus.&#xD;
      To date this has not been looked at in a systematic fashion.&#xD;
&#xD;
      There is also evidence to suggest that such goal directed therapy reduces the degree of&#xD;
      inflammation that invariably occurs after operations of this magnitude. It is hypothesized&#xD;
      that by resuscitating the endothelium more effectively with intravenous fluids that remain in&#xD;
      the intravascular space longer, there is less endothelial damage and thus less inflammation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2010</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Length of Stay</measure>
    <time_frame>Up to 180 days.</time_frame>
    <description>Patients will be assessed for fitness for hospital discharge. This will be used to calculate the length of stay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Crystalloid Use</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Colloid Use</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requirement for red blood cell transfusion</measure>
    <time_frame>7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluid balance</measure>
    <time_frame>7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine output</measure>
    <time_frame>7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine</measure>
    <time_frame>7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative complications</measure>
    <time_frame>28 days</time_frame>
    <description>Including: myocardial infarction, sepsis, pneumonia, renal failure, bleeding, ICU admission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutrophil gelatinase associated lipocalnin (NGAL) levels</measure>
    <time_frame>Pre-op, immediately post op, 6 hours post-op and 24 hours post-op</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Abdominal Aortic Aneurysm Uncomplicated</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV &gt;13%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fluid titrated at the discretion of the attending anesthesiologist.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV &gt;13%</intervention_name>
    <description>Following induction of anesthesia, Voluven boluses of 250ml will be given if SVV increases above 10%. Further Voluven boluses will be given in 250ml aliquots should the SVV increase to greater than 10%. If a total of 55ml/kg of Voluven is given, the fluid will be changed to lactated ringers and no further colloid will be given, as this is the maximum dose recommend by the manufacturer.&#xD;
Vasoactive agents (type and dose at the discretion of the attending anesthesiologist) may be given to maintain a mean arterial pressure that the clinical team feels adequate to maintain adequate organ perfusion. In the intervention group, however, vasoactive agents will not be given unless fluid administration has resulted in a maximal value of SV.</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluid titrated at the discretion of the attending anesthesiologist</intervention_name>
    <description>In the control group, the data from the FloTrac monitor will not be available to the anesthesia care provider. Fluid replacement will be at a rate and of a type that is entirely up to the anesthesiologist; the only stipulation being that Voluven is to be used should the provider desire to use a colloid solution.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists physical class I-III patients over the age of 18&#xD;
             years&#xD;
&#xD;
          -  Presenting for elective open repair of abdominal aortic aneurysms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Weight &gt;120kg&#xD;
&#xD;
          -  Known or suspected valvular aortic insufficiency&#xD;
&#xD;
          -  Renal Dysfunction (serum creatinine &gt;150 μmol/l)&#xD;
&#xD;
          -  Pre-existing bowel dysfunction&#xD;
&#xD;
          -  Active congestive heart failure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Duane J Funk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3T2N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2013</verification_date>
  <study_first_submitted>May 18, 2011</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>November 7, 2013</last_update_submitted>
  <last_update_submitted_qc>November 7, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 11, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Dr. Duane Funk</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm, Abdominal</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/NCT01681251
org study id: B2009:135
nct id: NCT01681251
lead sponsor: 
has dmc: No
The management and delivery of intravenous fluids during surgical operations is one of the
      important duties for anesthesiologists.

      The goal of this study was to determine if goal directed fluid therapy, titrated using the
      FloTrac monitor's measurement of stroke volume variation results in a decrease in the length
      of stay of patients undergoing open abdominal aneurysm repair.
The management and delivery of intravenous fluids during surgical operations is one of the
      important duties for anesthesiologists. There is a growing body of evidence that fluid
      overload in surgical patients is associated with decreased wound healing, slower return of
      gut function, anastomotic breakdown, pulmonary edema and post-operative visual changes.

      In the United States, abdominal aortic aneurysms are diagnosed in 190,000 people per year,
      and over 50,000 of those have the aneurysm repaired5. Recent advances in endovascular
      techniques have allowed many of these patients to forego an open repair. However, because of
      technical difficulties, many patients still require an open repair.

      The most common cause of morbidity in these patients is related to post-operative
      gastrointestinal tract dysfunction. This usually involves an adynamic ileus that the patients
      develop on the fourth post-operative day. This delays their tolerance of enteral foods and
      lengthens their hospital stay and hospital costs. It also has the potential of causing more
      morbidity in that patients may require total parenteral nutrition while awaiting return of
      bowel function.

      There are several causes of this gastrointestinal morbidity including direct mechanical
      trauma to the bowel during surgery and activation of the inflammatory cascade. These factors
      are unfortunately not modifiable by the team caring for the patient. One factor that is
      modifiable is the amount and type of intravenous fluids administered to the patient.

      Typically, anesthesiologists decide on the amount of fluid to administer to patients based on
      parameters such as heart rate, blood pressure and urine output. These are unfortunately
      unreliable in determining a patient's volume status, as these parameters can be within the
      normal range, and a patient might still have inadequate perfusion to their vital organs.
      Further, clinician's reliance on blood pressure as a target for fluid administration ignores
      the fact that organs require blood flow as well as pressure to function optimally. Until
      recently, the only way to measure blood flow was with the insertion of a pulmonary artery
      catheter. Based on several studies showing a lack of benefit of this invasive procedure, it
      has fallen out of favor in the non-cardiac arena. Newer monitors of cardiac output that can
      be attached to a patients arterial catheter (commonly placed for major surgical procedures)
      offer an alternative method for clinicians to measure cardiac output.

      One of these monitors, the FloTrac system (Edwards Life Sciences, Irvine CA), utilizes the
      arterial pulse contour to calculate cardiac output (CO) and the stroke volume variation (SVV)
      as a monitor of volume status. In patients who are mechanically ventilated there is a phasic
      variation in CO and stroke volume based on the ventilatory cycle. Large changes in stroke
      volume during the ventilatory cycle may indicate hypovolemia in patients. The administration
      of intravenous fluid to these patients results in a decrease in the SVV. Thus, the SVV can be
      use a volume monitor and used to titrate intravenous therapy. There have been several trials
      (mostly in colonic resection surgery) that have looked at such goal directed therapy with
      this and similar devices and have found a decrease in patient morbidity and length of stay.

      All of these studies have in common the use of a minimally invasive CO monitor and a reliance
      on colloids as the predominant fluid utilized during the case.

      The utilization of SVV to determine volume status is a novel approach to fluid management in
      surgical patients. As stated above, clinicians' historical reliance on pressures (such as as
      blood pressure and central venous pressure) to estimate intravascular volume status is based
      on an incomplete understanding on the factors that govern organ blood flow. To this end, the
      investigators will also assess several parameters during this study in an attempt to
      ascertain which is the best at predicting fluid responsiveness. Fluid responsiveness is
      defined as the ability to predict if a given patient will increase their CO to a fluid bolus.
      To date this has not been looked at in a systematic fashion.

      There is also evidence to suggest that such goal directed therapy reduces the degree of
      inflammation that invariably occurs after operations of this magnitude. It is hypothesized
      that by resuscitating the endothelium more effectively with intravenous fluids that remain in
      the intravascular space longer, there is less endothelial damage and thus less inflammation.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Length of Stay
time frame: Up to 180 days.
description: Patients will be assessed for fitness for hospital discharge. This will be used to calculate the length of stay.
measure: Total Crystalloid Use
time frame: 5 days
measure: Total Colloid Use
time frame: 5 days
measure: Requirement for red blood cell transfusion
time frame: 7 days
measure: Fluid balance
time frame: 7 days
measure: Urine output
time frame: 7 days
measure: Serum creatinine
time frame: 7 days
measure: Postoperative complications
time frame: 28 days
description: Including: myocardial infarction, sepsis, pneumonia, renal failure, bleeding, ICU admission.
measure: Neutrophil gelatinase associated lipocalnin (NGAL) levels
time frame: Pre-op, immediately post op, 6 hours post-op and 24 hours post-op
arm group label: Intervention
arm group type: Experimental
description: Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%
arm group label: Control
arm group type: Active Comparator
description: Fluid titrated at the discretion of the attending anesthesiologist.
intervention type: Other
intervention name: Fluid titrated with the use of arterial pulse contour cardiac output monitor if SVV >13%
description: Following induction of anesthesia, Voluven boluses of 250ml will be given if SVV increases above 10%. Further Voluven boluses will be given in 250ml aliquots should the SVV increase to greater than 10%. If a total of 55ml/kg of Voluven is given, the fluid will be changed to lactated ringers and no further colloid will be given, as this is the maximum dose recommend by the manufacturer.
Vasoactive agents (type and dose at the discretion of the attending anesthesiologist) may be given to maintain a mean arterial pressure that the clinical team feels adequate to maintain adequate organ perfusion. In the intervention group, however, vasoactive agents will not be given unless fluid administration has resulted in a maximal value of SV.
arm group label: Intervention
intervention type: Other
intervention name: Fluid titrated at the discretion of the attending anesthesiologist
description: In the control group, the data from the FloTrac monitor will not be available to the anesthesia care provider. Fluid replacement will be at a rate and of a type that is entirely up to the anesthesiologist; the only stipulation being that Voluven is to be used should the provider desire to use a colloid solution.
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Duane J Funk, MD
role: Principal Investigator
affiliation: University of Manitoba
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Dr. Duane Funk
investigator title: Assistant Professor
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Abdominal