<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/NCT04432610</url>
  </required_header>
  <id_info>
    <org_study_id>01-2020</org_study_id>
    <nct_id>NCT04432610</nct_id>
  </id_info>
  <brief_title>Echocardiographic Study of a Single Dose Bisoprolol Versus Nebivolol in Healthy Subjects</brief_title>
  <acronym>BINEB</acronym>
  <official_title>Echocardiographic Study of a Single Dose Bisoprolol Versus Nebivolol in Healthy Subjects: a Randomized, Double-blind, Cross-over Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clinical Hospital Center Zemun</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clinical Hospital Center Zemun</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>
      This is a randomized, double-blind, crossover study in healthy adult subjects. Each subject&#xD;
      will receive a single dose of bisoprolol 5 mg p.o. and nebivolol 5 mg p.o. with 1 week&#xD;
      washout period. All subjects will undergo a physical examination, 12-lead electrocardiography&#xD;
      and a comprehensive echocardiographic study before the administration of the study drug and 5&#xD;
      hours thereafter.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    COVID pandemic&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2030</start_date>
  <completion_date type="Anticipated">December 2030</completion_date>
  <primary_completion_date type="Anticipated">December 2030</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relative change (%) of cardiac output (CO)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>CO (l/min), will be assessed by calculating stroke volume using pulsed-wave doppler (velocity time integral)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of left ventricular ejection fraction (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Ejection fraction will be measured using modified Simpson rule</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of global longitudinal strain (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Global longitudinal strain will be assessed using speckle tracking echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of myocardial work (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Myocardial work will be assessed by using a dedicated commercially available software (GE, Norway)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of atrial function (ml)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Atrial function will be assessed by measuring phasic volume changes during diastole</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change of myocardial dispersion (ms)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Myocardial dispersion will be assessed by using speckle tracking echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of TAPSE (tricuspid annular plane systolic excursion, mm)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>TAPSE will be assessed by M-mode echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of blood pressure (mmHg)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Brachial blood pressure will be measured by sphygmomanometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes in atrial strain (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Atrial strain will be assessed using speckle tracking echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of electrical dispersion (ms)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Electrical dispersion will be assessed by using 12-lead electrocardiogram</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of right ventricular fractional area change (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>The parameter will be assessed by two-dimensional echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of heart rate (bpm)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Heart rate will be measured by 12-lead electrocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of left ventricular twist (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Twist will be assessed by speckle tracking echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of QTc interval (ms)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>QTc interval will be measured by using 12-lead electrocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of mitral E/A ratio (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>E/A ratio will be assessed by pulsed-wave Doppler</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative change of mitral E/e prime ratio (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>E/e prime ratio will be assessed by pulsed-wave and tissue Doppler echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative change of mitral E-wave deceleration time (ms)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>E-wave deceleration time will be measured by pulsed-wave Doppler echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and relative changes of right ventricular global longitudinal strain (%)</measure>
    <time_frame>Pre- and 5 hours post study drug administration</time_frame>
    <description>Global strain will be assessed by using speckle tracking echocardiography</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Bisoprolol Adverse Reaction</condition>
  <condition>Nebivolol Adverse Reaction</condition>
  <arm_group>
    <arm_group_label>Bisoprolol first, Nebivolol Second</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this arm, patient will first receive bisoprolol, and after 1 week washout period, nebivolol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nebivolol first, Bisoprolol second</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this arm, patient will first receive nebivolol, and after 1 week washout period, bisoprolol</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol versus Nebivolol</intervention_name>
    <description>All subjects will receive both drugs, but at different time periods determined by randomization, with 1 week washout period</description>
    <arm_group_label>Bisoprolol first, Nebivolol Second</arm_group_label>
    <arm_group_label>Nebivolol first, Bisoprolol second</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy subjects (male and female)&#xD;
&#xD;
          2. Age interval: 20-60 years old (inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any known absolute or relative contraindication to beta-blocker therapy&#xD;
&#xD;
          2. Poor echogenicity&#xD;
&#xD;
          3. A resting heart rate &lt;60 bpm&#xD;
&#xD;
          4. A resting blood pressure &lt; 110/70 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Hospital Centre Zemun</name>
      <address>
        <city>Belgrade</city>
        <zip>11080</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Clinical Hospital Center Zemun</investigator_affiliation>
    <investigator_full_name>Ivan Stankovic</investigator_full_name>
    <investigator_title>Head of Echocardiography</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nebivolol</mesh_term>
    <mesh_term>Bisoprolol</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/NCT04432610
org study id: 01-2020
nct id: NCT04432610
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a randomized, double-blind, crossover study in healthy adult subjects. Each subject
      will receive a single dose of bisoprolol 5 mg p.o. and nebivolol 5 mg p.o. with 1 week
      washout period. All subjects will undergo a physical examination, 12-lead electrocardiography
      and a comprehensive echocardiographic study before the administration of the study drug and 5
      hours thereafter.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Relative change (%) of cardiac output (CO)
time frame: Pre- and 5 hours post study drug administration
description: CO (l/min), will be assessed by calculating stroke volume using pulsed-wave doppler (velocity time integral)
measure: Absolute and relative changes of left ventricular ejection fraction (%)
time frame: Pre- and 5 hours post study drug administration
description: Ejection fraction will be measured using modified Simpson rule
measure: Absolute and relative changes of global longitudinal strain (%)
time frame: Pre- and 5 hours post study drug administration
description: Global longitudinal strain will be assessed using speckle tracking echocardiography
measure: Absolute and relative changes of myocardial work (%)
time frame: Pre- and 5 hours post study drug administration
description: Myocardial work will be assessed by using a dedicated commercially available software (GE, Norway)
measure: Absolute and relative changes of atrial function (ml)
time frame: Pre- and 5 hours post study drug administration
description: Atrial function will be assessed by measuring phasic volume changes during diastole
measure: Absolute change of myocardial dispersion (ms)
time frame: Pre- and 5 hours post study drug administration
description: Myocardial dispersion will be assessed by using speckle tracking echocardiography
measure: Absolute and relative changes of TAPSE (tricuspid annular plane systolic excursion, mm)
time frame: Pre- and 5 hours post study drug administration
description: TAPSE will be assessed by M-mode echocardiography
measure: Absolute and relative changes of blood pressure (mmHg)
time frame: Pre- and 5 hours post study drug administration
description: Brachial blood pressure will be measured by sphygmomanometer
measure: Absolute and relative changes in atrial strain (%)
time frame: Pre- and 5 hours post study drug administration
description: Atrial strain will be assessed using speckle tracking echocardiography
measure: Absolute and relative changes of electrical dispersion (ms)
time frame: Pre- and 5 hours post study drug administration
description: Electrical dispersion will be assessed by using 12-lead electrocardiogram
measure: Absolute and relative changes of right ventricular fractional area change (%)
time frame: Pre- and 5 hours post study drug administration
description: The parameter will be assessed by two-dimensional echocardiography
measure: Absolute and relative changes of heart rate (bpm)
time frame: Pre- and 5 hours post study drug administration
description: Heart rate will be measured by 12-lead electrocardiography
measure: Absolute and relative changes of left ventricular twist (%)
time frame: Pre- and 5 hours post study drug administration
description: Twist will be assessed by speckle tracking echocardiography
measure: Absolute and relative changes of QTc interval (ms)
time frame: Pre- and 5 hours post study drug administration
description: QTc interval will be measured by using 12-lead electrocardiography
measure: Absolute and relative changes of mitral E/A ratio (%)
time frame: Pre- and 5 hours post study drug administration
description: E/A ratio will be assessed by pulsed-wave Doppler
measure: Absolute and relative change of mitral E/e prime ratio (%)
time frame: Pre- and 5 hours post study drug administration
description: E/e prime ratio will be assessed by pulsed-wave and tissue Doppler echocardiography
measure: Absolute and relative change of mitral E-wave deceleration time (ms)
time frame: Pre- and 5 hours post study drug administration
description: E-wave deceleration time will be measured by pulsed-wave Doppler echocardiography
measure: Absolute and relative changes of right ventricular global longitudinal strain (%)
time frame: Pre- and 5 hours post study drug administration
description: Global strain will be assessed by using speckle tracking echocardiography
arm group label: Bisoprolol first, Nebivolol Second
arm group type: Experimental
description: In this arm, patient will first receive bisoprolol, and after 1 week washout period, nebivolol
arm group label: Nebivolol first, Bisoprolol second
arm group type: Experimental
description: In this arm, patient will first receive nebivolol, and after 1 week washout period, bisoprolol
intervention type: Drug
intervention name: Bisoprolol versus Nebivolol
description: All subjects will receive both drugs, but at different time periods determined by randomization, with 1 week washout period
arm group label: Bisoprolol first, Nebivolol Second
arm group label: Nebivolol first, Bisoprolol second
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Serbia
responsible party type: Principal Investigator
investigator affiliation: Clinical Hospital Center Zemun
investigator full name: Ivan Stankovic
investigator title: Head of Echocardiography
mesh term: Nebivolol
mesh term: Bisoprolol
sharing ipd: No