<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/NCT01704131</url>
  </required_header>
  <id_info>
    <org_study_id>ICCE12.001</org_study_id>
    <nct_id>NCT01704131</nct_id>
  </id_info>
  <brief_title>Levosimendan Pharmacokinetics in Children</brief_title>
  <acronym>LevoCorKids</acronym>
  <official_title>Pharmacokinetics of Levosimendan in Children With Acute Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Leiden University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Levosimendan is a drug used in patients with heart failure and has several advantages over&#xD;
      other heart failure drugs. A lot of research has been done with Levosimendan in Adults, and&#xD;
      the way the body handles the drug (pharmacokinetics) and responds to the drug&#xD;
      (pharmacodynamics) are well established. But, in children this information is lacking despite&#xD;
      the fact that Levosimendan is increasingly used in children of all ages. The investigators&#xD;
      aim to describe which Levosimendan dose leads to which drug levels in children of different&#xD;
      ages.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Levosimendan, a calcium-sensitizer, is a relatively new inotropic drug with the&#xD;
      benefit over conventional inotropes that it does not increase myocardial oxygen demand or&#xD;
      lead to arrhythmias. Levosimendan has a relatively unique pharmacokinetic profile, after a 24&#xD;
      hour infusion its clinical effects remain for several days. This is achieved through the&#xD;
      continuing haemodynamic effects of its active metabolites, which have a half life of&#xD;
      approximately 80 hours compared to 1 hour of Levosimendan itself. Levosimendan has been&#xD;
      extensively studied in adults and is used in ischemic heart disease, acute heart failure,&#xD;
      chronic heart failure, following cardiac surgery, and in septic shock. Due to the inotropic&#xD;
      properties and its strong pulmonary vasodilatory effect, Levosimendan could also be very&#xD;
      useful as perioperative therapy in children with congenital heart disease, low cardiac&#xD;
      output, or pulmonary artery hypertension.&#xD;
&#xD;
      Although experience with levosimendan in children is still scarce in the literature, initial&#xD;
      reports have been promising and Levosimendan is used more and more often as a (rescue)&#xD;
      therapy in children with heart failure. However, current dosing regimens in children are&#xD;
      based on adult pharmacokinetic evidence. One pediatric report suggests that the&#xD;
      pharmacokinetic profile of a single loading dose of Levosimendan is probably similar in&#xD;
      children older than 6 months compared to adults. The pharmacokinetic profile of a 24-hour&#xD;
      infusion of Levosimendan has not yet been studied in children. It is very important to study&#xD;
      the pharmacokinetics of this useful drug in different age groups because of the diversity of&#xD;
      the population due to age, volume of distribution, ontogeny of the metabolizing enzymes, and&#xD;
      the influence of disease state on pharmacokinetics and pharmacodynamics.&#xD;
&#xD;
      Objective: To describe the pharmacokinetic profile of a 24 hour infusion of levosimendan and&#xD;
      its active metabolites in children with acute or chronic heart failure.&#xD;
&#xD;
      Study design: Observational study of Levosimendan levels in children treated with&#xD;
      Levosimendan because of heart failure.&#xD;
&#xD;
      Study population: Children (&lt; 16 years) admitted to the pediatric intensive care unit, with&#xD;
      acute or chronic heart failure.&#xD;
&#xD;
      Intervention (if applicable): no intervention Main study parameters/endpoints: The primary&#xD;
      endpoint of the study is to describe the pharmacokinetic profile by determining plasma levels&#xD;
      of levosimendan and its metabolites during 12 days following a 24-hour infusion in children&#xD;
      with heart failure in different age groups. Secondary endpoints are the clinically measured&#xD;
      hemodynamic variables (heart rate, bloodpressure, lactate, troponin, pro-BNP, venous&#xD;
      saturation) and echocardiographic variables (ejection fraction, shortening fraction, tissue&#xD;
      Doppler) of all patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Anticipated">September 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2019</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>the pharmacokinetic profile of levosimendan and is metabolites</measure>
    <time_frame>3 years</time_frame>
    <description>AUC, Cmax, half-life, steady state concentration, plasma clearance, volume of distribution</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Acute Heart Failure</condition>
  <arm_group>
    <arm_group_label>children &gt; 6 months</arm_group_label>
    <description>children &gt; 6 months of age</description>
  </arm_group>
  <arm_group>
    <arm_group_label>children &lt; 6 months</arm_group_label>
    <description>children &lt; 6 months</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All children admitted to the Pediatric Intensive Care Unit with Acute Heart Failure who&#xD;
        will receive Levosimendan as part of their treatment.&#xD;
&#xD;
        Patients will receive Levosimendan whether they participate in the study (sampling&#xD;
        levosimendan levels) or not.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All children admitted to the Pediatric Intensive Care Unit with Acute Heart Failure&#xD;
             who will receive Levosimendan as part of their treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no informed consent&#xD;
&#xD;
          -  no sampling line&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter P Roeleveld, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leiden University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Heleen E Bunker-Wiersma, MD, phd</last_name>
    <role>Study Chair</role>
    <affiliation>Leiden University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peter P Roeleveld, MD</last_name>
    <phone>+31715261677</phone>
    <phone_ext>8486</phone_ext>
    <email>p.p.roeleveld@lumc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>H E Bunker-Wiersma, MD, Phd</last_name>
    <phone>+31715261677</phone>
    <phone_ext>8775</phone_ext>
    <email>H.E.Bunker-Wiersma@lumc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>PICU Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Peter P Roeleveld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>May 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>Peter Paul Roeleveld</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Levosimendan</keyword>
  <keyword>Children</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_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/NCT01704131
org study id: ICCE12.001
nct id: NCT01704131
lead sponsor: 
collaborator: 
has dmc: No
Levosimendan is a drug used in patients with heart failure and has several advantages over
      other heart failure drugs. A lot of research has been done with Levosimendan in Adults, and
      the way the body handles the drug (pharmacokinetics) and responds to the drug
      (pharmacodynamics) are well established. But, in children this information is lacking despite
      the fact that Levosimendan is increasingly used in children of all ages. The investigators
      aim to describe which Levosimendan dose leads to which drug levels in children of different
      ages.
Rationale: Levosimendan, a calcium-sensitizer, is a relatively new inotropic drug with the
      benefit over conventional inotropes that it does not increase myocardial oxygen demand or
      lead to arrhythmias. Levosimendan has a relatively unique pharmacokinetic profile, after a 24
      hour infusion its clinical effects remain for several days. This is achieved through the
      continuing haemodynamic effects of its active metabolites, which have a half life of
      approximately 80 hours compared to 1 hour of Levosimendan itself. Levosimendan has been
      extensively studied in adults and is used in ischemic heart disease, acute heart failure,
      chronic heart failure, following cardiac surgery, and in septic shock. Due to the inotropic
      properties and its strong pulmonary vasodilatory effect, Levosimendan could also be very
      useful as perioperative therapy in children with congenital heart disease, low cardiac
      output, or pulmonary artery hypertension.

      Although experience with levosimendan in children is still scarce in the literature, initial
      reports have been promising and Levosimendan is used more and more often as a (rescue)
      therapy in children with heart failure. However, current dosing regimens in children are
      based on adult pharmacokinetic evidence. One pediatric report suggests that the
      pharmacokinetic profile of a single loading dose of Levosimendan is probably similar in
      children older than 6 months compared to adults. The pharmacokinetic profile of a 24-hour
      infusion of Levosimendan has not yet been studied in children. It is very important to study
      the pharmacokinetics of this useful drug in different age groups because of the diversity of
      the population due to age, volume of distribution, ontogeny of the metabolizing enzymes, and
      the influence of disease state on pharmacokinetics and pharmacodynamics.

      Objective: To describe the pharmacokinetic profile of a 24 hour infusion of levosimendan and
      its active metabolites in children with acute or chronic heart failure.

      Study design: Observational study of Levosimendan levels in children treated with
      Levosimendan because of heart failure.

      Study population: Children (< 16 years) admitted to the pediatric intensive care unit, with
      acute or chronic heart failure.

      Intervention (if applicable): no intervention Main study parameters/endpoints: The primary
      endpoint of the study is to describe the pharmacokinetic profile by determining plasma levels
      of levosimendan and its metabolites during 12 days following a 24-hour infusion in children
      with heart failure in different age groups. Secondary endpoints are the clinically measured
      hemodynamic variables (heart rate, bloodpressure, lactate, troponin, pro-BNP, venous
      saturation) and echocardiographic variables (ejection fraction, shortening fraction, tissue
      Doppler) of all patients.
observational model: Cohort
time perspective: Prospective
measure: the pharmacokinetic profile of levosimendan and is metabolites
time frame: 3 years
description: AUC, Cmax, half-life, steady state concentration, plasma clearance, volume of distribution
arm group label: children > 6 months
description: children > 6 months of age
arm group label: children < 6 months
description: children < 6 months
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 16 Years
healthy volunteers: No
last name: Peter P Roeleveld, MD
role: Principal Investigator
affiliation: Leiden University Medical Center
last name: Heleen E Bunker-Wiersma, MD, phd
role: Study Chair
affiliation: Leiden University Medical Center
last name: Peter P Roeleveld, MD
phone: +31715261677
phone ext: 8486
email: p.p.roeleveld@lumc.nl
last name: H E Bunker-Wiersma, MD, Phd
phone: +31715261677
phone ext: 8775
email: H.E.Bunker-Wiersma@lumc.nl
facility: 
status: Recruiting
investigator: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: Peter Paul Roeleveld
investigator title: Principal Investigator
mesh term: Heart Failure