<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/NCT03266250</url>
  </required_header>
  <id_info>
    <org_study_id>ED399,09-24-2015</org_study_id>
    <nct_id>NCT03266250</nct_id>
  </id_info>
  <brief_title>Transthoracic Echocardiography of Inferior Vena Cava Before Spinal Anesthesia Can Predict Hypotension</brief_title>
  <official_title>Transthoracic Echocardiography of Inferior Vena Cava Before Spinal Anesthesia Can Predict Hypotension in Elderly Orthopaedic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National and Kapodistrian University of Athens</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>
      Study Protocol: Outcome Measurements Primary Outcome The main outcome will be the&#xD;
      preoperative performance of the dIVCmax/IVCCI ratio to foresee the incidence of hypotension&#xD;
      after spinal anesthesia in a greater extent to that of the established IVCCI measurements.&#xD;
&#xD;
      Secondary Outcomes To identify other echocardiographic or clinical measurements that can&#xD;
      predict an intraoperative spinal-induced haemodynamic instability.&#xD;
&#xD;
      Sample Size Calculation A pilot study of 20 patients revealed a detected area under the ROC&#xD;
      curve (AUC) of 0,91 for dIVCmax/IVCCI and for dIVCmax 0,82 with rank correlation between the&#xD;
      two assays being 0.87 in both positive and negative cases. Based on this result, a sample of&#xD;
      56 patients will achieve 80% power to detect significant difference (at a level 0.05) between&#xD;
      dIVCmax/IVCCI and dIVCmax.&#xD;
&#xD;
      Potential Benefits of the Study The results of this study will allow us to determine which&#xD;
      clinical or US-measurement can yield better performance so as a preoperative prediction of&#xD;
      spinal-induced hypotension can be achieved; that way these measurements can permit and guide&#xD;
      a targeted preoperative fluid challenges prior to the implementation of spinal anesthesia&#xD;
      Potential Side Effects of the Study Participation in this protocol will not put patients at&#xD;
      higher risk for complications since we do not perform any intervention (either&#xD;
      pharmacological or surgical) There will be no occupational risks to researchers or&#xD;
      assistants. Proposed Timetable According to the exclusion criteria and taking into account&#xD;
      the number of cases performed in our department per monthly basis, it should take us&#xD;
      approximately 6 months to recruit 60 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AIM OF THE STUDY&#xD;
&#xD;
      We hypothesized, therefore, that the preoperative dIVCmax/IVCCI ratio (maximum diameter of&#xD;
      inferior vena cava-IVC- at the expiration = dIVCmax and the collapsibility index of the IVC&#xD;
      =IVCCI) could greater foresee the incidence of hypotension after spinal anesthesia than the&#xD;
      established IVCCI measurements. In light of this hypothesis, we prospectively examined both&#xD;
      the dIVCmax/IVCCI ratio and IVCCI before spinal anesthesia in a population who fulfilled&#xD;
      predetermined inclusion criteria and we set out to evaluate the diagnostic performance of&#xD;
      this indices in predicting spinal-induced hypotension.&#xD;
&#xD;
      METHODOLOGY In the present observational prospective study, consecutive sampling is used to&#xD;
      recruit ageing patients (&gt;70 years) who sustained orthopaedic operation under spinal&#xD;
      anesthesia.&#xD;
&#xD;
      According to our department policy, the documentation of a cardiac disease in our patients&#xD;
      takes place during the routine preoperative anesthetic evaluation always with the cooperation&#xD;
      of consultant cardiologists. Patients' medical history, physical examination, ECG, and X-ray&#xD;
      assessment are standard practice supplemented by specific exams or tests Echocardiogrphic&#xD;
      protocol and measurements A TTE is performed in all patients before spinal anaesthesia (Vivid&#xD;
      T8, GE Healthcare, Waukesha, Wisconsin, USA) equipped with a 2-5 MHz phased array transducer.&#xD;
      All echocardiograms is carried out by the same anesthesiologist/intensivist (TS), who has 12&#xD;
      years of experience in perioperative echocardiography. All data are saved and stored&#xD;
      digitally for off-line analysis.&#xD;
&#xD;
      A standard intraoperative TTE protocol is being used in all patients. and included the&#xD;
      following views: subxiphoid4-chamber (SUBX), apical 4-chamber (4CH), apical 2-chamber (2CH),&#xD;
      apical 3-chamber (3CH), parasternal long (LAX) and short axis (SAX) windows.&#xD;
&#xD;
      All data are saved and stored digitally for off-line postoperative analysis. The Ejection&#xD;
      Fraction (EF) is determined using the Simpson's method. Patients with EF lower than 50% do&#xD;
      not continue for the study. The global longitudinal peak systolic strain (GLPSS) is used to&#xD;
      assess LV mechanics in the longitudinal axis of LV motion. The TAPSE index is employed for&#xD;
      the assessment of the right ventricular function. LV filling pressures in diastole is&#xD;
      estimated by the E/Em ratio (E=peak velocity flow in early diastole, Em=the average of peak&#xD;
      velocities in early diastole of lateral and septal mitral annulus). In addition, LV&#xD;
      dimensions and wall thickness are measured either in short or long parasternal axis view.&#xD;
      Stroke volume of the LV is assessed by VTILVOT (pulsed-wave Doppler of velocity time integral&#xD;
      in the LV outflow tract).&#xD;
&#xD;
      IVC measurements included its maximum diameter at the end of expiration (dIVCmax), IVCCI&#xD;
      during spontaneous in quite breathing, [(IVC maximal diameter - IVC minimal diameter)/IVC&#xD;
      maximal diameter] and the ratio (R) of dIVCmax/IVCCI; the IVC diameters were measured in the&#xD;
      long axis of the IVC and just proximal to the entry of the hepatic veins.&#xD;
&#xD;
      Anesthetic protocol and measurements. Spinal anaesthesia is introduced with a single&#xD;
      intrathecal injection of 0.75% plain ropivacaine using a 22 or 25-gauge needle with the&#xD;
      patient in the lateral or sitting position. The dose range is 12mg to 18mg, depending on age&#xD;
      and height. Perioperative hemodynamic monitoring is carried out with an indwelling radial&#xD;
      artery catheter. Patients with intraoperative mean blood pressure (MBP) ≤65 mmHg, or &lt;25% of&#xD;
      its baseline preoperative value were considered hypotensive. Arterial hypotension related to&#xD;
      bone cement application, tourniquet deflation, overt intraoperative/postoperative bleeding&#xD;
      (blood loss&gt;150cc) or patients receiving blood transfusion for any reason were not&#xD;
      considered.&#xD;
&#xD;
      Statistical analysis Sample size: A pilot study of 20 patients revealed a detected area under&#xD;
      the ROC curve (AUC) of 0,91 for dIVCmax/IVCCI and for dIVCmax 0,82 with rank correlation&#xD;
      between the two assays being 0.87 in both positive and negative cases. Based on this result,&#xD;
      a sample of 56 patients achieved 80% power to detect significant difference (at a level 0.05)&#xD;
      between dIVCmax/IVCCI and dIVCmax.&#xD;
&#xD;
      Data analysis: Quantitative variables and proportions will be compared with the student&#xD;
      t-test and chi-square test respectively. Normality was tested by using the Kolmogorov-Smirnov&#xD;
      test. Receiver operating characteristic (ROC) curve analysis will be performed to evaluate&#xD;
      the diagnostic performance of clinical/Doppler parameters in identifying patients who&#xD;
      experienced spinal-induced hypotension. The area under the curve (AUC) and the respective 95%&#xD;
      confidence interval (95% CI) are estimated according to Hanley and McNeil. 1 The AUC curves&#xD;
      are compared using the method described by DeLong et al. 2. The results are expressed as&#xD;
      percentage (%) or mean ± SD; a p value of &lt;0.05 is considered statistically significant.&#xD;
      Statistical analysis will be done with statistical analysis software (SPSS, 17.0, Chicago,&#xD;
      IL; MedCalc Software, Mariakerke, Belgium).&#xD;
&#xD;
        1. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating&#xD;
           characteristic (ROC) curve. Radiology 1982 ;143:29-36&#xD;
&#xD;
        2. DeLong ER, DeLong DM, Clarke- Pearson DL. Comparing the areas under two or more&#xD;
           correlate receiver operating characteristic curves: a nonparametric approach. Biometrics&#xD;
           1988; 44:837-845&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 15, 2017</start_date>
  <completion_date type="Actual">July 20, 2018</completion_date>
  <primary_completion_date type="Actual">July 20, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Preoperative performance of the dIVCmax/IVCCI ratio</measure>
    <time_frame>6 months</time_frame>
    <description>The main outcome will be the preoperative performance of the dIVCmax/IVCCI ratio to foresee the incidence of hypotension after spinal anesthesia in a greater extent to that of the established IVCCI measurements</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Echocardiographic or clinical measurements</measure>
    <time_frame>6 months</time_frame>
    <description>To identify other echocardiographic or clinical measurements that can predict an intraoperative spinal-induced haemodynamic instability</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">70</enrollment>
  <condition>Spinal Anesthetic Toxicity</condition>
  <condition>Inferior Vena Cava Abnormality</condition>
  <condition>Intraoperative Complications</condition>
  <arm_group>
    <arm_group_label>spinal anesthesia Hypotensive patients</arm_group_label>
    <description>Transthoracic echocardiography of IVC before spinal anaesthesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>spinal anesthesia Normotensive patients</arm_group_label>
    <description>Transthoracic echocardiography of IVC before spinal anaesthesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>spinal anesthesia</intervention_name>
    <description>Transthoracic echocardiography of inferior vena cava before spinal anesthesia</description>
    <arm_group_label>spinal anesthesia Hypotensive patients</arm_group_label>
    <arm_group_label>spinal anesthesia Normotensive patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Elderly orthopaedic patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria: patients with AHA/ACC stage I, II or III with their cardiac disease&#xD;
        status in compensated status -&#xD;
&#xD;
        Exclusion Criteria: patients with AHA/ACC stage IV&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theodosis Saranteas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National and Kapodistrian University of Athens, School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ATTIKON University General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attika</state>
        <zip>15562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>Zhang J, Critchley LA. Inferior Vena Cava Ultrasonography before General Anesthesia Can Predict Hypotension after Induction. Anesthesiology. 2016 Mar;124(3):580-9. doi: 10.1097/ALN.0000000000001002.</citation>
    <PMID>26771910</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 20, 2018</last_update_submitted>
  <last_update_submitted_qc>August 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
    <investigator_full_name>Theodosis Saranteas, MD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>inferior vena caca ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
    <mesh_term>Intraoperative Complications</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <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/NCT03266250
org study id: ED399,09-24-2015
nct id: NCT03266250
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Study Protocol: Outcome Measurements Primary Outcome The main outcome will be the
      preoperative performance of the dIVCmax/IVCCI ratio to foresee the incidence of hypotension
      after spinal anesthesia in a greater extent to that of the established IVCCI measurements.

      Secondary Outcomes To identify other echocardiographic or clinical measurements that can
      predict an intraoperative spinal-induced haemodynamic instability.

      Sample Size Calculation A pilot study of 20 patients revealed a detected area under the ROC
      curve (AUC) of 0,91 for dIVCmax/IVCCI and for dIVCmax 0,82 with rank correlation between the
      two assays being 0.87 in both positive and negative cases. Based on this result, a sample of
      56 patients will achieve 80% power to detect significant difference (at a level 0.05) between
      dIVCmax/IVCCI and dIVCmax.

      Potential Benefits of the Study The results of this study will allow us to determine which
      clinical or US-measurement can yield better performance so as a preoperative prediction of
      spinal-induced hypotension can be achieved; that way these measurements can permit and guide
      a targeted preoperative fluid challenges prior to the implementation of spinal anesthesia
      Potential Side Effects of the Study Participation in this protocol will not put patients at
      higher risk for complications since we do not perform any intervention (either
      pharmacological or surgical) There will be no occupational risks to researchers or
      assistants. Proposed Timetable According to the exclusion criteria and taking into account
      the number of cases performed in our department per monthly basis, it should take us
      approximately 6 months to recruit 60 patients.
AIM OF THE STUDY

      We hypothesized, therefore, that the preoperative dIVCmax/IVCCI ratio (maximum diameter of
      inferior vena cava-IVC- at the expiration = dIVCmax and the collapsibility index of the IVC
      =IVCCI) could greater foresee the incidence of hypotension after spinal anesthesia than the
      established IVCCI measurements. In light of this hypothesis, we prospectively examined both
      the dIVCmax/IVCCI ratio and IVCCI before spinal anesthesia in a population who fulfilled
      predetermined inclusion criteria and we set out to evaluate the diagnostic performance of
      this indices in predicting spinal-induced hypotension.

      METHODOLOGY In the present observational prospective study, consecutive sampling is used to
      recruit ageing patients (>70 years) who sustained orthopaedic operation under spinal
      anesthesia.

      According to our department policy, the documentation of a cardiac disease in our patients
      takes place during the routine preoperative anesthetic evaluation always with the cooperation
      of consultant cardiologists. Patients' medical history, physical examination, ECG, and X-ray
      assessment are standard practice supplemented by specific exams or tests Echocardiogrphic
      protocol and measurements A TTE is performed in all patients before spinal anaesthesia (Vivid
      T8, GE Healthcare, Waukesha, Wisconsin, USA) equipped with a 2-5 MHz phased array transducer.
      All echocardiograms is carried out by the same anesthesiologist/intensivist (TS), who has 12
      years of experience in perioperative echocardiography. All data are saved and stored
      digitally for off-line analysis.

      A standard intraoperative TTE protocol is being used in all patients. and included the
      following views: subxiphoid4-chamber (SUBX), apical 4-chamber (4CH), apical 2-chamber (2CH),
      apical 3-chamber (3CH), parasternal long (LAX) and short axis (SAX) windows.

      All data are saved and stored digitally for off-line postoperative analysis. The Ejection
      Fraction (EF) is determined using the Simpson's method. Patients with EF lower than 50% do
      not continue for the study. The global longitudinal peak systolic strain (GLPSS) is used to
      assess LV mechanics in the longitudinal axis of LV motion. The TAPSE index is employed for
      the assessment of the right ventricular function. LV filling pressures in diastole is
      estimated by the E/Em ratio (E=peak velocity flow in early diastole, Em=the average of peak
      velocities in early diastole of lateral and septal mitral annulus). In addition, LV
      dimensions and wall thickness are measured either in short or long parasternal axis view.
      Stroke volume of the LV is assessed by VTILVOT (pulsed-wave Doppler of velocity time integral
      in the LV outflow tract).

      IVC measurements included its maximum diameter at the end of expiration (dIVCmax), IVCCI
      during spontaneous in quite breathing, [(IVC maximal diameter - IVC minimal diameter)/IVC
      maximal diameter] and the ratio (R) of dIVCmax/IVCCI; the IVC diameters were measured in the
      long axis of the IVC and just proximal to the entry of the hepatic veins.

      Anesthetic protocol and measurements. Spinal anaesthesia is introduced with a single
      intrathecal injection of 0.75% plain ropivacaine using a 22 or 25-gauge needle with the
      patient in the lateral or sitting position. The dose range is 12mg to 18mg, depending on age
      and height. Perioperative hemodynamic monitoring is carried out with an indwelling radial
      artery catheter. Patients with intraoperative mean blood pressure (MBP) ≤65 mmHg, or <25% of
      its baseline preoperative value were considered hypotensive. Arterial hypotension related to
      bone cement application, tourniquet deflation, overt intraoperative/postoperative bleeding
      (blood loss>150cc) or patients receiving blood transfusion for any reason were not
      considered.

      Statistical analysis Sample size: A pilot study of 20 patients revealed a detected area under
      the ROC curve (AUC) of 0,91 for dIVCmax/IVCCI and for dIVCmax 0,82 with rank correlation
      between the two assays being 0.87 in both positive and negative cases. Based on this result,
      a sample of 56 patients achieved 80% power to detect significant difference (at a level 0.05)
      between dIVCmax/IVCCI and dIVCmax.

      Data analysis: Quantitative variables and proportions will be compared with the student
      t-test and chi-square test respectively. Normality was tested by using the Kolmogorov-Smirnov
      test. Receiver operating characteristic (ROC) curve analysis will be performed to evaluate
      the diagnostic performance of clinical/Doppler parameters in identifying patients who
      experienced spinal-induced hypotension. The area under the curve (AUC) and the respective 95%
      confidence interval (95% CI) are estimated according to Hanley and McNeil. 1 The AUC curves
      are compared using the method described by DeLong et al. 2. The results are expressed as
      percentage (%) or mean ± SD; a p value of <0.05 is considered statistically significant.
      Statistical analysis will be done with statistical analysis software (SPSS, 17.0, Chicago,
      IL; MedCalc Software, Mariakerke, Belgium).

        1. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating
           characteristic (ROC) curve. Radiology 1982 ;143:29-36

        2. DeLong ER, DeLong DM, Clarke- Pearson DL. Comparing the areas under two or more
           correlate receiver operating characteristic curves: a nonparametric approach. Biometrics
           1988; 44:837-845
observational model: Other
time perspective: Prospective
measure: Preoperative performance of the dIVCmax/IVCCI ratio
time frame: 6 months
description: The main outcome will be the preoperative performance of the dIVCmax/IVCCI ratio to foresee the incidence of hypotension after spinal anesthesia in a greater extent to that of the established IVCCI measurements
measure: Echocardiographic or clinical measurements
time frame: 6 months
description: To identify other echocardiographic or clinical measurements that can predict an intraoperative spinal-induced haemodynamic instability
arm group label: spinal anesthesia Hypotensive patients
description: Transthoracic echocardiography of IVC before spinal anaesthesia
arm group label: spinal anesthesia Normotensive patients
description: Transthoracic echocardiography of IVC before spinal anaesthesia
intervention type: Procedure
intervention name: spinal anesthesia
description: Transthoracic echocardiography of inferior vena cava before spinal anesthesia
arm group label: spinal anesthesia Hypotensive patients
arm group label: spinal anesthesia Normotensive patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Theodosis Saranteas, MD
role: Principal Investigator
affiliation: National and Kapodistrian University of Athens, School of Medicine
facility: 
country: Greece
citation: Zhang J, Critchley LA. Inferior Vena Cava Ultrasonography before General Anesthesia Can Predict Hypotension after Induction. Anesthesiology. 2016 Mar;124(3):580-9. doi: 10.1097/ALN.0000000000001002.
PMID: 26771910
responsible party type: Principal Investigator
investigator affiliation: National and Kapodistrian University of Athens
investigator full name: Theodosis Saranteas, MD
investigator title: Assistant Professor
mesh term: Hypotension
mesh term: Intraoperative Complications
mesh term: Anesthetics
sharing ipd: No