<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/NCT03262480</url>
  </required_header>
  <id_info>
    <org_study_id>MD/17.07.27</org_study_id>
    <nct_id>NCT03262480</nct_id>
  </id_info>
  <brief_title>The Stroke Volume Optimization of Goal Directed Fluid Therapy During Radical Cystectomy</brief_title>
  <official_title>Perioperative Goal Directed Fluid Therapy During Radical Cystectomy: the Impact of Stroke Volume Optimization vs Dynamic Central Venous Pressure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University</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>
      Although fluid therapy is of paramount value in anesthetic practice, there is no guideline&#xD;
      available for perioperative fluid management in major abdominal surgery. So, there is a need&#xD;
      to establish whether goal directed fluid therapy protocol is effective during radical&#xD;
      cystectomy and urinary diversion. A balance of perioperative fluid therapy is crucial, yet&#xD;
      the method to achieve this equilibrium remains a highly debated subject. Therefore, this&#xD;
      study will be designed to investigate the effects of two individualized goal directed fluid&#xD;
      therapy during radical cystectomy to encourage an effective circulating blood volume and&#xD;
      pressure. Accordingly, as a primary outcome, the investigators assume that stroke volume&#xD;
      optimization could maintain better perioperative hemodynamic stability with low incidence and&#xD;
      severity of hypotensive episodes together with achievement of maximal oxygenation. Hopefully&#xD;
      this regimen could help to decrease the possibility of perioperative tissue hypoperfusion and&#xD;
      the possible associated complications as a secondary outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study protocol:&#xD;
&#xD;
      Patients will be randomly assigned to one of two equal groups, according to&#xD;
      computer-generated randomization sequence into:&#xD;
&#xD;
        -  Stroke volume optimization group (SVO group).&#xD;
&#xD;
        -  Central venous pressure dynamic group(CVPdyngroup).&#xD;
&#xD;
      Stroke volume optimization group (SVO group):&#xD;
&#xD;
      Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4 (Voluven, Fresenius kabi,&#xD;
      Deutschland GmbH, Bad Homburg, Germany) will be administered within 10 minutes and stroke&#xD;
      volume response will be recorded .If stroke volume increase by more than 10 % for 20 minutes,&#xD;
      the aliquot will be repeated. No further aliquots will be given once stroke volume failed to&#xD;
      increase &gt;10%. The last stroke volume without rise of &gt; 10% will be defined as optimum stroke&#xD;
      volume (SVopt).When stroke volume decreases by 10% below (SVopt), this will be defined as&#xD;
      trigger stroke volume (SVT). Stroke volume will be followed every 30 minutes during surgery&#xD;
      and every 4 hours for 24 hours postoperatively .&#xD;
&#xD;
      Central venous pressure dynamic group (CVPdyn group):&#xD;
&#xD;
      Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4(Voluven) will be administered&#xD;
      within 10 minutes and CVP response will be recorded. If CVP failed to rise sustainably for&#xD;
      more than 2 mmHg for 20 minutes, the aliquot will be repeated. No further aliquots will be&#xD;
      given once CVP increases more than 2 mmHg above the recorded one.The last CVP with sustained&#xD;
      rise of&gt;2 mmHg will be defined as CVP maximum (CVPmax).When CVP decrease below (CVPmax)by 3&#xD;
      mmHg, this will be defined as trigger CVP (CVPT).CVP will be followed every 30 min during&#xD;
      surgery and every 4 hours for 24 hours postoperatively&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">December 10, 2020</completion_date>
  <primary_completion_date type="Actual">August 1, 2020</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>
    <intervention_model_description>Two groups:&#xD;
Stroke volume optimization group (SVO group).&#xD;
Central venous pressure dynamic group(CVPdyngroup).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>The management will be carried out by a member of research team only aware of allocation group. The attending anesthesiologist, surgeons and nursing staff will be totally blind of randomization schedule or the hydration regimen used. All postoperative clinical staff handling patient care will be also unaware of the aim of the work.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Perioperative hypotension</measure>
    <time_frame>perioperative</time_frame>
    <description>Mean arterial blood pressure &lt; 65mmHg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximal tissue oxygenation</measure>
    <time_frame>perioperative</time_frame>
    <description>Oxygen delivery index &gt; 550 ml/min/m2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Medical postoperative complication</measure>
    <time_frame>48 hours postoperative</time_frame>
    <description>Acute kidney injury (AKI) . Postoperative serum creatinine value is either more than 1.5-fold or more than 0.3 mg/dl before surgery within 48 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical postoperative complication</measure>
    <time_frame>7-days postoperative</time_frame>
    <description>Nausea, vomiting, abdominal distension, anastomotic leakage, paralytic ileus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anesthetic postoperative complication</measure>
    <time_frame>24 hours postoperative</time_frame>
    <description>Cardiogenic pulmonary edema.Cardiac index &lt; 2.5 l/min/m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical postoperative complication</measure>
    <time_frame>7-days postoperative</time_frame>
    <description>Wound infection and burst abdomen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory postoperative complication</measure>
    <time_frame>7-days postoperative</time_frame>
    <description>Pneumonia, acute respiratory distress, postoperative ventilation and ICU admission.length of ICU stay in days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative complication</measure>
    <time_frame>7-days postoperative</time_frame>
    <description>mortality</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">172</enrollment>
  <condition>Radical Cystectomy</condition>
  <arm_group>
    <arm_group_label>Stroke volume optimization</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4 (Voluven) will be administered within 10 minutes and stroke volume response will be recorded .If stroke volume increase by more than 10 % for 20 minutes, the aliquot will be repeated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Central venous pressure dynamic</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4(Voluven) will be administered within 10 minutes and CVP response will be recorded. If CVP failed to rise sustainably for more than 2 mmHg for 20 minutes, the aliquot will be repeated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>stroke volume optimization</intervention_name>
    <description>Hemodynamic variables including stroke volume (SV), stroke volume variation (SVV), stroke volume index (SVI), cardiac output (COP), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), thoracic fluid content (TFC), corrected flow time (FTC), index of contractility (ICON), systolic time ratio (STR), oxygen delivery (DO2) and oxygen delivery index (DO2I) will be measured by Cardiac output non-invasive monitor (ICONTM, OSYPKA medical cardiotronic GMBH, Elixir, Germany). Heart rate (HR), mean arterial blood pressure (MAP), central venous pressure (CVP) and arterial oxygen saturation (Sao2) will be measured using HP monitor.&#xD;
If mean arterial blood pressure(MAP) drops below 65 mmHg despite achievement of SVopt and CVPmax in both groups, a bolus dose of 5 mg ephedrine will be given and repeated as needed .Norepinephrine will be given for persistent hypotension.Dobutamine 5 mic/kg/min will be started if cardiac index less than 2.5 l/m2.</description>
    <arm_group_label>Central venous pressure dynamic</arm_group_label>
    <arm_group_label>Stroke volume optimization</arm_group_label>
    <other_name>central venous pressure dynamic</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with American Society of Anesthesiologists (ASA) physical status I - II&#xD;
             scheduled for radical cystectomy and urinary diversion for muscle invasive urinary&#xD;
             bladder carcinoma .&#xD;
&#xD;
          -  Both sexes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients younger than 18 years&#xD;
&#xD;
          -  Body mass index (BMI) &lt; 25 and &gt;35.&#xD;
&#xD;
          -  Patients with any contraindications to epidural anesthesia (patient refusal, local&#xD;
             skin infection, previous spine surgery and coagulopathy).&#xD;
&#xD;
          -  Those with known allergy to local anesthetics.&#xD;
&#xD;
          -  Patients with major cardiovascular problems with ejection fraction &lt; 40 .&#xD;
&#xD;
          -  Renal impairment with serum creatinine &gt;1.8 mg/dl&#xD;
&#xD;
          -  Patients with hepatic dysfunction will be excluded.&#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>Mahmoud M Othman, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mansoura faculty of medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Urology and nephrology center</name>
      <address>
        <city>Mansoura</city>
        <state>El-Dakahlia</state>
        <zip>+2050</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>December 20, 2020</last_update_submitted>
  <last_update_submitted_qc>December 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Mahmoud Mahmoud Othman</investigator_full_name>
    <investigator_title>professor of Anesthesia and surgical ICU</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03262480
org study id: MD/17.07.27
nct id: NCT03262480
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Although fluid therapy is of paramount value in anesthetic practice, there is no guideline
      available for perioperative fluid management in major abdominal surgery. So, there is a need
      to establish whether goal directed fluid therapy protocol is effective during radical
      cystectomy and urinary diversion. A balance of perioperative fluid therapy is crucial, yet
      the method to achieve this equilibrium remains a highly debated subject. Therefore, this
      study will be designed to investigate the effects of two individualized goal directed fluid
      therapy during radical cystectomy to encourage an effective circulating blood volume and
      pressure. Accordingly, as a primary outcome, the investigators assume that stroke volume
      optimization could maintain better perioperative hemodynamic stability with low incidence and
      severity of hypotensive episodes together with achievement of maximal oxygenation. Hopefully
      this regimen could help to decrease the possibility of perioperative tissue hypoperfusion and
      the possible associated complications as a secondary outcome.
Study protocol:

      Patients will be randomly assigned to one of two equal groups, according to
      computer-generated randomization sequence into:

        -  Stroke volume optimization group (SVO group).

        -  Central venous pressure dynamic group(CVPdyngroup).

      Stroke volume optimization group (SVO group):

      Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4 (Voluven, Fresenius kabi,
      Deutschland GmbH, Bad Homburg, Germany) will be administered within 10 minutes and stroke
      volume response will be recorded .If stroke volume increase by more than 10 % for 20 minutes,
      the aliquot will be repeated. No further aliquots will be given once stroke volume failed to
      increase >10%. The last stroke volume without rise of > 10% will be defined as optimum stroke
      volume (SVopt).When stroke volume decreases by 10% below (SVopt), this will be defined as
      trigger stroke volume (SVT). Stroke volume will be followed every 30 minutes during surgery
      and every 4 hours for 24 hours postoperatively .

      Central venous pressure dynamic group (CVPdyn group):

      Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4(Voluven) will be administered
      within 10 minutes and CVP response will be recorded. If CVP failed to rise sustainably for
      more than 2 mmHg for 20 minutes, the aliquot will be repeated. No further aliquots will be
      given once CVP increases more than 2 mmHg above the recorded one.The last CVP with sustained
      rise of>2 mmHg will be defined as CVP maximum (CVPmax).When CVP decrease below (CVPmax)by 3
      mmHg, this will be defined as trigger CVP (CVPT).CVP will be followed every 30 min during
      surgery and every 4 hours for 24 hours postoperatively
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two groups:
Stroke volume optimization group (SVO group).
Central venous pressure dynamic group(CVPdyngroup).
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: The management will be carried out by a member of research team only aware of allocation group. The attending anesthesiologist, surgeons and nursing staff will be totally blind of randomization schedule or the hydration regimen used. All postoperative clinical staff handling patient care will be also unaware of the aim of the work.
measure: Perioperative hypotension
time frame: perioperative
description: Mean arterial blood pressure < 65mmHg
measure: Maximal tissue oxygenation
time frame: perioperative
description: Oxygen delivery index > 550 ml/min/m2
measure: Medical postoperative complication
time frame: 48 hours postoperative
description: Acute kidney injury (AKI) . Postoperative serum creatinine value is either more than 1.5-fold or more than 0.3 mg/dl before surgery within 48 hours
measure: Surgical postoperative complication
time frame: 7-days postoperative
description: Nausea, vomiting, abdominal distension, anastomotic leakage, paralytic ileus
measure: Anesthetic postoperative complication
time frame: 24 hours postoperative
description: Cardiogenic pulmonary edema.Cardiac index < 2.5 l/min/m2
measure: Surgical postoperative complication
time frame: 7-days postoperative
description: Wound infection and burst abdomen
measure: Respiratory postoperative complication
time frame: 7-days postoperative
description: Pneumonia, acute respiratory distress, postoperative ventilation and ICU admission.length of ICU stay in days.
measure: Postoperative complication
time frame: 7-days postoperative
description: mortality
arm group label: Stroke volume optimization
arm group type: Active Comparator
description: Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4 (Voluven) will be administered within 10 minutes and stroke volume response will be recorded .If stroke volume increase by more than 10 % for 20 minutes, the aliquot will be repeated.
arm group label: Central venous pressure dynamic
arm group type: Sham Comparator
description: Colloid aliquots of 200 ml 6% hydroxy ethyl starch 130/ 0.4(Voluven) will be administered within 10 minutes and CVP response will be recorded. If CVP failed to rise sustainably for more than 2 mmHg for 20 minutes, the aliquot will be repeated.
intervention type: Other
intervention name: stroke volume optimization
description: Hemodynamic variables including stroke volume (SV), stroke volume variation (SVV), stroke volume index (SVI), cardiac output (COP), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), thoracic fluid content (TFC), corrected flow time (FTC), index of contractility (ICON), systolic time ratio (STR), oxygen delivery (DO2) and oxygen delivery index (DO2I) will be measured by Cardiac output non-invasive monitor (ICONTM, OSYPKA medical cardiotronic GMBH, Elixir, Germany). Heart rate (HR), mean arterial blood pressure (MAP), central venous pressure (CVP) and arterial oxygen saturation (Sao2) will be measured using HP monitor.
If mean arterial blood pressure(MAP) drops below 65 mmHg despite achievement of SVopt and CVPmax in both groups, a bolus dose of 5 mg ephedrine will be given and repeated as needed .Norepinephrine will be given for persistent hypotension.Dobutamine 5 mic/kg/min will be started if cardiac index less than 2.5 l/m2.
arm group label: Central venous pressure dynamic
arm group label: Stroke volume optimization
other name: central venous pressure dynamic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mahmoud M Othman, Professor
role: Principal Investigator
affiliation: Mansoura faculty of medicine
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Mahmoud Mahmoud Othman
investigator title: professor of Anesthesia and surgical ICU
sharing ipd: Undecided