<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/NCT03245996</url>
  </required_header>
  <id_info>
    <org_study_id>14058</org_study_id>
    <nct_id>NCT03245996</nct_id>
  </id_info>
  <brief_title>The Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker</brief_title>
  <official_title>The Impact of Heart Rate on Central Hemodynamics in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tartu University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tartu University Hospital</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 study is divided into two parts:&#xD;
&#xD;
        -  The first part evaluates the acute effect of non-pharmacological heart rate change on&#xD;
           central hemodynamic parameters noninvasively in sick sinus syndrome patients with a&#xD;
           permanent cardiac pacemaker&#xD;
&#xD;
        -  The second part evaluates the acute effects of atenolol, nebivolol and ivabradine on&#xD;
           central hemodynamic parameters noninvasively in sick sinus syndrome patients with a&#xD;
           permanent cardiac pacemaker at different pacing rate levels&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with sick sinus syndrome and a double-chamber cardiac pacemaker are studied.&#xD;
&#xD;
        -  To investigate the role of non-pharmacological heart rate change on central hemodynamics&#xD;
           in the first part of the study, the investigators acutely change pacing rate from atrial&#xD;
           paced-atrial sensed (AAI)-mode 60 to 40 to 90 bpm and obtain hemodynamic parameters&#xD;
           noninvasively after a short stabilisation period after each pacemaker rate change.&#xD;
&#xD;
        -  Subsequently, to investigate the acute effects of beta-blockers or ivabradine on central&#xD;
           hemodynamics in the second part of the study, the investigators obtain central&#xD;
           hemodynamic parameters noninvasively after acute administration of atenolol, nebivolol&#xD;
           or ivabradine at the same pacing rate levels used in the first part of the study&#xD;
           (AAI-mode 60, 40 and 90 bpm).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single</masking>
  </study_design_info>
  <primary_outcome>
    <measure>First part of the study: central systolic blood pressure</measure>
    <time_frame>3 minutes after heart rate change</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Second part of the study: systolic blood pressure amplification</measure>
    <time_frame>3 hours after drug administration and 3 minutes after heart rate change</time_frame>
    <description>difference between peripheral and central systolic blood pressure</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Aortic Blood Pressure</condition>
  <arm_group>
    <arm_group_label>Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with a cardiac pacemaker</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AAI 40 bpm</intervention_name>
    <description>Cardiac pacemaker of the subjects is set to AAI-mode 40 bpm in the first and second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AAI 60 bpm</intervention_name>
    <description>Cardiac pacemaker of the subjects is set to AAI-mode 60 bpm in the first and second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AAI 90 bpm</intervention_name>
    <description>Cardiac pacemaker of the subjects is set to AAI-mode 90 bpm in the first and second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atenolol Pill</intervention_name>
    <description>50 or 100 mg of atenolol is administered to subjects in the second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nebivolol Pill</intervention_name>
    <description>5 mg of nebivolol is administered to subjects in the second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivabradine Pill</intervention_name>
    <description>5 or 7,5 mg of ivabradine is administered to subjects in the second part of the study</description>
    <arm_group_label>Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 18-75 years;&#xD;
&#xD;
          -  dual-chamber pacemaker implanted due to sick sinus syndrome at least six months&#xD;
             before; sinus rhythm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  average seated office brachial systolic BP ≥160 mmHg and/or diastolic BP ≥ 100 mmHg;&#xD;
             atrial pacing &lt;40%;&#xD;
&#xD;
          -  ventricular pacing &gt;25%;&#xD;
&#xD;
          -  unpaced QRS &gt;120 ms and/or QTc &gt;500 ms on 12-lead ECG;&#xD;
&#xD;
          -  atrioventricular blockage at AAI-mode 90 bpm; resting HR &gt;60 bpm at AAI-mode 40 bpm;&#xD;
             irregular heart rate;&#xD;
&#xD;
          -  automatic mode switching &gt;10%;&#xD;
&#xD;
          -  implantable cardioverter defibrillator or cardiac resynchronisation therapy pacemaker;&#xD;
             treatment with digoxin, class Ic or III antiarrhythmic drugs;&#xD;
&#xD;
          -  history of acute coronary syndrome;&#xD;
&#xD;
          -  stable angina pectoris;&#xD;
&#xD;
          -  heart failure with reduced left ventricular ejection fraction;&#xD;
&#xD;
          -  history of cerebrovascular event;&#xD;
&#xD;
          -  diabetes mellitus;&#xD;
&#xD;
          -  chronic kidney disease with eGFR &lt;30 ml/min/m2;&#xD;
&#xD;
          -  peripheral artery disease;&#xD;
&#xD;
          -  clinically relevant heart valve disease;&#xD;
&#xD;
          -  active cancer;&#xD;
&#xD;
          -  acute or chronic inflammatory disease;&#xD;
&#xD;
          -  severe chronic respiratory or liver disease;&#xD;
&#xD;
          -  pregnancy or breastfeeding&#xD;
&#xD;
          -  contraindication or intolerance to atenolol, nebivolol, ivabradine or adjuvants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>July 6, 2018</last_update_submitted>
  <last_update_submitted_qc>July 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tartu University Hospital</investigator_affiliation>
    <investigator_full_name>Tuuli Teeäär</investigator_full_name>
    <investigator_title>PhD Student, cardiologist</investigator_title>
  </responsible_party>
  <keyword>sick sinus syndrome</keyword>
  <keyword>heart rate</keyword>
  <keyword>aortic blood pressure</keyword>
  <keyword>artificial pacemaker</keyword>
  <keyword>beta-blockers</keyword>
  <keyword>ivabradine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sick Sinus Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atenolol</mesh_term>
    <mesh_term>Nebivolol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>all data shared after completion of study as supplement to journal article</ipd_description>
  </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/NCT03245996
org study id: 14058
nct id: NCT03245996
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is divided into two parts:

        -  The first part evaluates the acute effect of non-pharmacological heart rate change on
           central hemodynamic parameters noninvasively in sick sinus syndrome patients with a
           permanent cardiac pacemaker

        -  The second part evaluates the acute effects of atenolol, nebivolol and ivabradine on
           central hemodynamic parameters noninvasively in sick sinus syndrome patients with a
           permanent cardiac pacemaker at different pacing rate levels
Patients with sick sinus syndrome and a double-chamber cardiac pacemaker are studied.

        -  To investigate the role of non-pharmacological heart rate change on central hemodynamics
           in the first part of the study, the investigators acutely change pacing rate from atrial
           paced-atrial sensed (AAI)-mode 60 to 40 to 90 bpm and obtain hemodynamic parameters
           noninvasively after a short stabilisation period after each pacemaker rate change.

        -  Subsequently, to investigate the acute effects of beta-blockers or ivabradine on central
           hemodynamics in the second part of the study, the investigators obtain central
           hemodynamic parameters noninvasively after acute administration of atenolol, nebivolol
           or ivabradine at the same pacing rate levels used in the first part of the study
           (AAI-mode 60, 40 and 90 bpm).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: Single
measure: First part of the study: central systolic blood pressure
time frame: 3 minutes after heart rate change
measure: Second part of the study: systolic blood pressure amplification
time frame: 3 hours after drug administration and 3 minutes after heart rate change
description: difference between peripheral and central systolic blood pressure
arm group label: Subjects
arm group type: Experimental
description: Subjects with a cardiac pacemaker
intervention type: Device
intervention name: AAI 40 bpm
description: Cardiac pacemaker of the subjects is set to AAI-mode 40 bpm in the first and second part of the study
arm group label: Subjects
intervention type: Device
intervention name: AAI 60 bpm
description: Cardiac pacemaker of the subjects is set to AAI-mode 60 bpm in the first and second part of the study
arm group label: Subjects
intervention type: Device
intervention name: AAI 90 bpm
description: Cardiac pacemaker of the subjects is set to AAI-mode 90 bpm in the first and second part of the study
arm group label: Subjects
intervention type: Drug
intervention name: Atenolol Pill
description: 50 or 100 mg of atenolol is administered to subjects in the second part of the study
arm group label: Subjects
intervention type: Drug
intervention name: Nebivolol Pill
description: 5 mg of nebivolol is administered to subjects in the second part of the study
arm group label: Subjects
intervention type: Drug
intervention name: Ivabradine Pill
description: 5 or 7,5 mg of ivabradine is administered to subjects in the second part of the study
arm group label: Subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Tartu University Hospital
investigator full name: Tuuli Teeäär
investigator title: PhD Student, cardiologist
mesh term: Sick Sinus Syndrome
mesh term: Atenolol
mesh term: Nebivolol
sharing ipd: Yes
ipd description: all data shared after completion of study as supplement to journal article