<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/NCT03779178</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL16_0743</org_study_id>
    <secondary_id>2018-000307-17</secondary_id>
    <nct_id>NCT03779178</nct_id>
  </id_info>
  <brief_title>Landiolol in Postoperative Atrial Fibrillation</brief_title>
  <acronym>MMELPOAF</acronym>
  <official_title>Microcirculatory and Macrocirculatory Effects of Landiolol in Prevention of Postoperative Atrial Fibrillation: a Randomized Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Postoperative atrial fibrillation is a common complication after cardiac surgery and is&#xD;
      associated with an elevation of morbidity and mortality. The recommended treatment includes&#xD;
      heart rate control with a beta blocker. Landiolol is a new-generation beta-blocker with&#xD;
      favourable pharmacologic properties making an interesting drug to treat postoperative atrial&#xD;
      fibrillation. However, Landiolol micro and macrocirculatory effects in the setting of atrial&#xD;
      fibrillation are yet to describe. The aim of this study is to describe microcirculatory&#xD;
      effects of incremental doses of landiolol in postoperative atrial fibrillation compared to a&#xD;
      placebo. Our hypothesis is Landiolol will improve microcirculation disorders.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Actual">December 4, 2019</completion_date>
  <primary_completion_date type="Actual">December 4, 2019</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 20 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 40 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 60 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 80 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 100 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microcirculatory mean flow index (MIF) acquired by sublingual microscopy</measure>
    <time_frame>at 120 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of perfused vessels acquired by sublingual microscopy</measure>
    <time_frame>at 120 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>functional capillary density acquired by sublingual microscopy</measure>
    <time_frame>at 120 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>De Backer score acquired by sublingual microscopy</measure>
    <time_frame>at 120 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>heterogeneity of the mean flow index acquired by sublingual microscopy</measure>
    <time_frame>at 120 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>systolic arterial pressure</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>diastolic arterial pressure</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cardiac output measured by transthoracic echocardiography</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>systemic vascular resistance</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial elastance.</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>hemodynamic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ejection fraction of the left ventricle (FEVG)</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>telesystolic volumes of the right ventricle</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>telesystolic volumes of the left ventricle</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>telediastolic volumes of the right ventricle</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>telediastolic volumes of the left ventricle</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>right ventricle contractility (measured with TAPSE and tricuspid S-wave)</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intracardiac filling pressure profiles (E/a, E/Vp, E/e')</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>echocardiographic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>oxygen consumption (V02)</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>tissular perfusion parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>oxygen delivery (DO2),</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>tissular perfusion parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>carbon dioxide production (VCO2)</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>tissular perfusion parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial lactate</measure>
    <time_frame>at 120 minutes</time_frame>
    <description>tissular perfusion parameters</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Landiolol group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Landiolol perfusion in incremental doses (range 0.5 to 10 µg/kg/min) over 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo perfusion in incremental doses (range 0.03 to 0.6 mL/kg/h) over 2 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Landiolol</intervention_name>
    <description>Landiolol perfusion over 120 minutes in incremental doses : 0.5, 1, 2, 5 and 10 µg/kg/min. Doses are modified every 20 minutes</description>
    <arm_group_label>Landiolol group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo perfusion is sodium chloride NaCl 0.9% over 120 minutes in incremental doses : 0.03, 0.06, 0.12, 0.3 and 0.6 mL/kg/h. Doses are modified every 20 minutes. Perfusion are similar in landiolol group to preserve blind.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient underwent conventional cardiac surgery&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Writing contentment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing chronic atrial fibrillation&#xD;
&#xD;
          -  Contraindication to beta-blockers&#xD;
&#xD;
          -  Circulatory shock (cardiac index&lt;2.2 L/min and lactate&gt;4mmol/L)&#xD;
&#xD;
          -  Distributive shock (cardiac index&gt;2.2 L/min with norepinephrine dose &gt; 0.3 µg/kg/min&#xD;
             to reach mean arterial pressure &gt; 65mmHg).&#xD;
&#xD;
          -  Acute respiratory distress&#xD;
&#xD;
          -  Major bleeding (&gt;200mL/h)&#xD;
&#xD;
          -  Patient already included into an interventional clinical study&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  No social security insurance&#xD;
&#xD;
          -  Patient not able to give consent (curators, patients deprived of public rights)&#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>Matthias Jacquet-Lagrèze</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospices Civils de Lyon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Louis Pradel</name>
      <address>
        <city>Bron</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>landiolol</keyword>
  <keyword>microcirculation</keyword>
  <keyword>cardiac surgery</keyword>
  <keyword>atrial fibrillation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Landiolol</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/NCT03779178
org study id: 69HCL16_0743
secondary id: 2018-000307-17
nct id: NCT03779178
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Postoperative atrial fibrillation is a common complication after cardiac surgery and is
      associated with an elevation of morbidity and mortality. The recommended treatment includes
      heart rate control with a beta blocker. Landiolol is a new-generation beta-blocker with
      favourable pharmacologic properties making an interesting drug to treat postoperative atrial
      fibrillation. However, Landiolol micro and macrocirculatory effects in the setting of atrial
      fibrillation are yet to describe. The aim of this study is to describe microcirculatory
      effects of incremental doses of landiolol in postoperative atrial fibrillation compared to a
      placebo. Our hypothesis is Landiolol will improve microcirculation disorders.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 20 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 40 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 60 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 80 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 100 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)
time frame: at 120 minutes
description: Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.
measure: Microcirculatory mean flow index (MIF) acquired by sublingual microscopy
time frame: at 120 minutes
measure: proportion of perfused vessels acquired by sublingual microscopy
time frame: at 120 minutes
measure: functional capillary density acquired by sublingual microscopy
time frame: at 120 minutes
measure: De Backer score acquired by sublingual microscopy
time frame: at 120 minutes
measure: heterogeneity of the mean flow index acquired by sublingual microscopy
time frame: at 120 minutes
measure: Heart rate
time frame: at 120 minutes
description: hemodynamic parameters
measure: systolic arterial pressure
time frame: at 120 minutes
description: hemodynamic parameters
measure: diastolic arterial pressure
time frame: at 120 minutes
description: hemodynamic parameters
measure: cardiac output measured by transthoracic echocardiography
time frame: at 120 minutes
description: hemodynamic parameters
measure: systemic vascular resistance
time frame: at 120 minutes
description: hemodynamic parameters
measure: arterial elastance.
time frame: at 120 minutes
description: hemodynamic parameters
measure: Ejection fraction of the left ventricle (FEVG)
time frame: at 120 minutes
description: echocardiographic parameters
measure: telesystolic volumes of the right ventricle
time frame: at 120 minutes
description: echocardiographic parameters
measure: telesystolic volumes of the left ventricle
time frame: at 120 minutes
description: echocardiographic parameters
measure: telediastolic volumes of the right ventricle
time frame: at 120 minutes
description: echocardiographic parameters
measure: telediastolic volumes of the left ventricle
time frame: at 120 minutes
description: echocardiographic parameters
measure: right ventricle contractility (measured with TAPSE and tricuspid S-wave)
time frame: at 120 minutes
description: echocardiographic parameters
measure: intracardiac filling pressure profiles (E/a, E/Vp, E/e')
time frame: at 120 minutes
description: echocardiographic parameters
measure: oxygen consumption (V02)
time frame: at 120 minutes
description: tissular perfusion parameters
measure: oxygen delivery (DO2),
time frame: at 120 minutes
description: tissular perfusion parameters
measure: carbon dioxide production (VCO2)
time frame: at 120 minutes
description: tissular perfusion parameters
measure: arterial lactate
time frame: at 120 minutes
description: tissular perfusion parameters
arm group label: Landiolol group
arm group type: Experimental
description: Landiolol perfusion in incremental doses (range 0.5 to 10 µg/kg/min) over 2 hours
arm group label: Placebo group
arm group type: Placebo Comparator
description: Placebo perfusion in incremental doses (range 0.03 to 0.6 mL/kg/h) over 2 hours
intervention type: Drug
intervention name: Landiolol
description: Landiolol perfusion over 120 minutes in incremental doses : 0.5, 1, 2, 5 and 10 µg/kg/min. Doses are modified every 20 minutes
arm group label: Landiolol group
intervention type: Drug
intervention name: Placebo
description: Placebo perfusion is sodium chloride NaCl 0.9% over 120 minutes in incremental doses : 0.03, 0.06, 0.12, 0.3 and 0.6 mL/kg/h. Doses are modified every 20 minutes. Perfusion are similar in landiolol group to preserve blind.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Matthias Jacquet-Lagrèze
role: Principal Investigator
affiliation: Hospices Civils de Lyon
facility: 
country: France
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Landiolol