<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/NCT02188888</url>
  </required_header>
  <id_info>
    <org_study_id>2309</org_study_id>
    <nct_id>NCT02188888</nct_id>
  </id_info>
  <brief_title>Echocardiographic and Arterial Pressure Waveform Changes After Reducing Heart Rate With Esmolol in Septic Shock Patients</brief_title>
  <official_title>Heart Rate Reduction With Esmolol is Associated With Improved Arterial Elastance in Patients With Septic Shock. A Prospective Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical study suggests that beta-blockers by decreasing heart rate together with an increase&#xD;
      in stroke volume do not negatively affect cardiac output allowing an economization of cardiac&#xD;
      work and oxygen consumption in patients with septic shock. Whether this hemodynamic profile&#xD;
      leads to an amelioration of myocardial performance is still unclear. The objective of the&#xD;
      present study is therefore to elucidate whether a reduction in heart rate with esmolol is&#xD;
      associated to an improvement of cardiac efficiency in patients with septic shock who remained&#xD;
      tachycardic after hemodynamic optimization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After 24-36 hours of initial hemodynamic stabilization, 44 septic shock patients with heart&#xD;
      rate &gt; of 95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP)&#xD;
      between 65 and 75 mmHg despite adequate volume resuscitation,will receive a continuous&#xD;
      esmolol infusion to maintain heart rate between 94 and 80 bpm. Norepinephrine will be&#xD;
      titrated to achieve a MAP between 65 and 75 mmHg. To investigate myocardial performance, we&#xD;
      will simultaneously assess LV ejection fraction (LVEF), tricuspidal annular plane solid&#xD;
      excursion (TAPSE) by echocardiography, the dP/dt MAX and the cardiac cycle efficiency (CCE)&#xD;
      both estimated from the arterial pressure waveform. Finally we will analyze changes in static&#xD;
      arterial elastance. Data will be obtained at baseline and after four hours once achieved the&#xD;
      predefined heart rate threshold.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>heart rate</measure>
    <time_frame>over a period of four hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>echocardiography</measure>
    <time_frame>over a period of four hours</time_frame>
    <description>LV ejection fraction (LVEF) and tricuspidal annular plane solid excursion (TAPSE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>static arterial elastance</measure>
    <time_frame>over a period of four hours</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>arterial pressure waveform</measure>
    <time_frame>over a period of four hours</time_frame>
    <description>systolic, diastolic and dicrotic pressures</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">45</enrollment>
  <condition>Tachycardia</condition>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>Tachycardic patients</arm_group_label>
    <description>Patients will receive a continuous esmolol infusion to maintain heart rate between 94 and 80 bpm. Norepinephrine will be titrated to achieve a MAP between 65 and 75 mmHg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>esmolol</intervention_name>
    <description>Strict heart rate control: esmolol at any dose to maintain heart rate between 95 and 80 bpm</description>
    <arm_group_label>Tachycardic patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Septic shock patients with heart rate &gt; of 95 bpm and requiring norepinephrine to maintain&#xD;
        mean arterial pressure (MAP) between 65 and 75 mmHg after at least 24 hours of hemodynamic&#xD;
        optimization.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  septic shock criteria&#xD;
&#xD;
          -  presence of heart rate &gt; 95 bpm.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  age &lt; 18&#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>Andrea Morelli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Roma La Sapienza</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Anesthesiology and Intensive care of the University of Rome La Sapienza</name>
      <address>
        <city>Rome</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>August 6, 2015</last_update_submitted>
  <last_update_submitted_qc>August 6, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 7, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Andrea Morelli</investigator_full_name>
    <investigator_title>associate professor</investigator_title>
  </responsible_party>
  <keyword>septic shock</keyword>
  <keyword>esmolol</keyword>
  <keyword>tachycardia</keyword>
  <keyword>betablockers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esmolol</mesh_term>
  </intervention_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/NCT02188888
org study id: 2309
nct id: NCT02188888
lead sponsor: 
has dmc: No
Clinical study suggests that beta-blockers by decreasing heart rate together with an increase
      in stroke volume do not negatively affect cardiac output allowing an economization of cardiac
      work and oxygen consumption in patients with septic shock. Whether this hemodynamic profile
      leads to an amelioration of myocardial performance is still unclear. The objective of the
      present study is therefore to elucidate whether a reduction in heart rate with esmolol is
      associated to an improvement of cardiac efficiency in patients with septic shock who remained
      tachycardic after hemodynamic optimization.
After 24-36 hours of initial hemodynamic stabilization, 44 septic shock patients with heart
      rate > of 95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP)
      between 65 and 75 mmHg despite adequate volume resuscitation,will receive a continuous
      esmolol infusion to maintain heart rate between 94 and 80 bpm. Norepinephrine will be
      titrated to achieve a MAP between 65 and 75 mmHg. To investigate myocardial performance, we
      will simultaneously assess LV ejection fraction (LVEF), tricuspidal annular plane solid
      excursion (TAPSE) by echocardiography, the dP/dt MAX and the cardiac cycle efficiency (CCE)
      both estimated from the arterial pressure waveform. Finally we will analyze changes in static
      arterial elastance. Data will be obtained at baseline and after four hours once achieved the
      predefined heart rate threshold.
observational model: Cohort
time perspective: Prospective
measure: heart rate
time frame: over a period of four hours
measure: echocardiography
time frame: over a period of four hours
description: LV ejection fraction (LVEF) and tricuspidal annular plane solid excursion (TAPSE)
measure: static arterial elastance
time frame: over a period of four hours
measure: arterial pressure waveform
time frame: over a period of four hours
description: systolic, diastolic and dicrotic pressures
arm group label: Tachycardic patients
description: Patients will receive a continuous esmolol infusion to maintain heart rate between 94 and 80 bpm. Norepinephrine will be titrated to achieve a MAP between 65 and 75 mmHg.
intervention type: Drug
intervention name: esmolol
description: Strict heart rate control: esmolol at any dose to maintain heart rate between 95 and 80 bpm
arm group label: Tachycardic patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrea Morelli, MD
role: Principal Investigator
affiliation: University of Roma La Sapienza
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Andrea Morelli
investigator title: associate professor
mesh term: Shock, Septic
mesh term: Tachycardia
mesh term: Shock
mesh term: Esmolol