<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/NCT03764722</url>
  </required_header>
  <id_info>
    <org_study_id>KB 431/2018</org_study_id>
    <nct_id>NCT03764722</nct_id>
  </id_info>
  <brief_title>Effectiveness of a Repetitive Use of 24-hour Levosimendan Infusions in Patients With Severe Systolic Heart Failure in Order to Prevent Rehospitalizations</brief_title>
  <official_title>Effectiveness of a Repetitive Use of 24-hour Levosimendan Infusions in Patients With Severe Systolic Heart Failure in Order to Prevent Rehospitalizations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Collegium Medicum w Bydgoszczy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Collegium Medicum w Bydgoszczy</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rehospitalizations due to exacerbation of chronic heart failure are an important problem for&#xD;
      patients suffering from heart failure.&#xD;
&#xD;
      Rehospitalzations lead to worse prognosis, have an impact on the quality of life and have a&#xD;
      negative financial impact on the health care system.&#xD;
&#xD;
      Currently, studies are being conducted on the efficacy of levosimendan in the prevention of&#xD;
      heart failure exacerbations. Patients receive levosimendan at repetitive use and preliminary&#xD;
      results suggest a reduction in the incidence of exacerbations of heart failure.&#xD;
&#xD;
      Thanks to the clinical trial planned in the Department of Cardiology of the Biziel Hospital&#xD;
      with repeatable use of levosimendan, it is possible to determine the benefits of this method&#xD;
      of treatment more accurately.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Heart failure affects 12% of the adult population and its frequency increases with age and&#xD;
      affects 10% of people over 70 years old. Heart failure is characterized by high annual death&#xD;
      rate reaching 17% and the percentage of rehospitalization at the level of 44% annually. In&#xD;
      order to reduce morbidity and mortality rates in the case of heart failure, many diagnostic&#xD;
      and therapeutic methods have been introduced over the last few years, however the prognosis&#xD;
      for this medical condition is still unfavorable nonetheless.&#xD;
&#xD;
      Rehospitalizations due to exacerbation of chronic heart failure are an important problem for&#xD;
      patients suffering from heart failure.&#xD;
&#xD;
      Rehospitalzations lead to worse prognosis, have an impact on the quality of life and have a&#xD;
      negative financial impact on the health care system. At the moment, there are numerous&#xD;
      clinical trials aimed at improving the prognosis of patients with heart failure.&#xD;
&#xD;
      Levosimendan is a modern drug registered in the treatment of acute heart failure. In the&#xD;
      current ESC guidelines for the treatment of patients with acute heart failure, levosimendan&#xD;
      is mainly recommended for the group of patients chronically treated with beta-adrenolytics&#xD;
      and in the treatment of a peri-infarction shock.&#xD;
&#xD;
      It is a substance with inotropic positive and vasodilating effects. It belongs to the group&#xD;
      of drugs sensitizing contractile elements of a myocardium on calcium ions. In the clinical&#xD;
      trials and meta-analyses, the safety profile of levosimendan is better in comparison to the&#xD;
      classical pressure amines used in the treatment of acute heart failure: dobutamine and&#xD;
      dopamine. Beneficial clinical effect of levosimendan is prolonged beyond the period of its&#xD;
      direct use due to the active metabolites remaining in the bloodstream.&#xD;
&#xD;
      Currently, studies are being conducted on the efficacy of levosimendan in the prevention of&#xD;
      heart failure exacerbations. Patients receive levosimendan at repetitive use and preliminary&#xD;
      results suggest a reduction in the incidence of exacerbations of heart failure. Due to the&#xD;
      low number of patients included in individual centers and non-homogeneous protocols of the&#xD;
      use of levosimendan in repeated infusions, the benefits of using this method of treatment can&#xD;
      not be clearly determined at present. Thanks to the clinical trial planned in the Department&#xD;
      of Cardiology of the Biziel Hospital with repeatable use of levosimendan, it is possible to&#xD;
      determine the benefits of this method of treatment more accurately.&#xD;
&#xD;
      Levosimendan is a drug with a beneficial safety profile, and the most common side effect,&#xD;
      which is hypotension, will disappear shortly after discontinuation of treatment or after an&#xD;
      infusion of crystalloids. Patients will be hospitalized at ITK, where a standard physical&#xD;
      examination will be conducted. The patient will fill in the SF36 questionnaire before the&#xD;
      treatment to self-evaluate his or hers quality of life. The patient will take medication&#xD;
      according to the latest outpatient recommendations.&#xD;
&#xD;
      During the 24-hour treatment, blood pressure will be monitored (until the target dose is&#xD;
      set). The heart rate will be monitored continuously (for the next 2 hours every 30 minutes,&#xD;
      then every 1 hour). Daily balance of fluids will be administered.&#xD;
&#xD;
      The patient will initially receive a standard dose of 0.1 mcg/kgmc/min. In case of good&#xD;
      tolerance of the drug - the dose will be increased to 0.2 mcg/kgmc/min. If hypotension SBP&#xD;
      &lt;90 mmHg occurs, the dose will be reduced to 0.05 mcg / kgm / min. If the hypotension&#xD;
      persists despite the reduction of the drug - the infusion will be terminated and the patient&#xD;
      will be excluded from the study. The infusion will be terminated within 24 hours, the patient&#xD;
      will be examined again 4 hours after the end of the infusion, by the attending physician and&#xD;
      unless there are contraindications - discharged home.&#xD;
&#xD;
      Patients will be hospitalized every 4 weeks for the next 6 months with the above-mentioned&#xD;
      parameters from the peripheral blood and march test, before the next dose. The control test&#xD;
      will also include the determination of the concentration of levosimendan metabolites prior to&#xD;
      the next infusion.&#xD;
&#xD;
      During the last follow-up visit, echocardiography and spiroergometry testing will be&#xD;
      performed before the next dosage.&#xD;
&#xD;
      After the 12 months of inclusion in the study, a telephone interview will be conducted in the&#xD;
      direction of rehospitalization due to exacerbation of heart failure.&#xD;
&#xD;
      The data obtained from the study will be compared with the standard parameters of&#xD;
      rehospitalization due to the exacerbation of heart failure included in the ESC guidelines.&#xD;
      The variability of data obtained from the quality of life questionnaire at the beginning and&#xD;
      at the end of the study will also be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of rehospitalisations in patients with severe heart failure treated with 24-hour levosimendan infusions</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life in patients with severe heart failure treated with 24-hour levosimendan infusions.</measure>
    <time_frame>from baseline up to 4 weeks during 6 months</time_frame>
    <description>via SF-36 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sodium in patients with severe heart failure treated with 24-hour: SF-36 questionnaire levosimendan infusions.</measure>
    <time_frame>from baseline up to 4 weeks during 6 months</time_frame>
    <description>counted in mmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in kaldyum in patients with severe heart failure treated with 24-hour levosimendan infusions.</measure>
    <time_frame>from baseline up to 4 weeks during 6 months</time_frame>
    <description>counted in mmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NT-proBNP in patients with severe heart failure treated with 24-hour levosimendan infusions.</measure>
    <time_frame>from baseline and up to 4 weeks during 6 months.</time_frame>
    <description>counted in ng/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in troponin T in patients with severe heart failure treated with 24-hour levosimendan infusions.</measure>
    <time_frame>from baseline and up to 4 weeks during 6 months.</time_frame>
    <description>counted in μg/l</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Systolic Heart Failure</condition>
  <arm_group>
    <arm_group_label>Levosimendan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levosimendan</intervention_name>
    <description>The patient will initially receive a standard dose of 0.1 mcg/kgmc/min. In case of good tolerance of the drug - the dose will be increased to 0.2 mcg/kgmc/min. If hypotension SBP &lt;90 mmHg occurs, the dose will be reduced to 0.05 mcg / kgm / min. If the hypotension persists despite the reduction of the drug - the infusion will be terminated and the patient will be excluded from the study. The infusion will be terminated within 24 hours, the patient will be examined again 4 hours after the end of the infusion, by the attending physician and unless there are contraindications - discharged home.&#xD;
Patients will be hospitalized every 4 weeks for the next 6 months.</description>
    <arm_group_label>Levosimendan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - at least 2 hospitalizations due to exacerbation of chronic heart failure with reduction&#xD;
        of left ventricular ejection fraction (EF&lt; 40%) during last 6 months, despite optimal heart&#xD;
        failure treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chronic kidney disease (GFR &lt; 30)&#xD;
&#xD;
          -  severe liver damage (AT 5x &gt; N, bilirubin &gt;2,0 g/dl)&#xD;
&#xD;
          -  hypotonia&#xD;
&#xD;
          -  hypokalemia&#xD;
&#xD;
          -  HGB&lt;10g/dl&#xD;
&#xD;
          -  severe aortic and mitral stenosis&#xD;
&#xD;
          -  tachycardia &gt;100/min or atrial fibrillation with HR &gt; 120/min&#xD;
&#xD;
          -  features of hypovolemia&#xD;
&#xD;
          -  levosimendan intolerance&#xD;
&#xD;
          -  acute infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grzegorz Grześk, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Collegium Medicum w Bydgoszczy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Małgorzata Dobosiewicz, PhD</last_name>
    <phone>48602288918</phone>
    <email>margotd@poczta.onet.pl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wojciech Hertmanowski, MD</last_name>
    <phone>48505518399</phone>
    <email>woj.hertmanowski@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Second Department of Cardiology</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>July 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>December 4, 2018</last_update_submitted>
  <last_update_submitted_qc>December 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Collegium Medicum w Bydgoszczy</investigator_affiliation>
    <investigator_full_name>Małgorzata Dobosiewicz, PhD</investigator_full_name>
    <investigator_title>Professor Grzegorz Grześk</investigator_title>
  </responsible_party>
  <keyword>Levosimendan</keyword>
  <keyword>Rehospitalisation</keyword>
  <keyword>Heart failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Heart Failure, Systolic</mesh_term>
    <mesh_term>Systolic Murmurs</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simendan</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/NCT03764722
org study id: KB 431/2018
nct id: NCT03764722
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Rehospitalizations due to exacerbation of chronic heart failure are an important problem for
      patients suffering from heart failure.

      Rehospitalzations lead to worse prognosis, have an impact on the quality of life and have a
      negative financial impact on the health care system.

      Currently, studies are being conducted on the efficacy of levosimendan in the prevention of
      heart failure exacerbations. Patients receive levosimendan at repetitive use and preliminary
      results suggest a reduction in the incidence of exacerbations of heart failure.

      Thanks to the clinical trial planned in the Department of Cardiology of the Biziel Hospital
      with repeatable use of levosimendan, it is possible to determine the benefits of this method
      of treatment more accurately.
Heart failure affects 12% of the adult population and its frequency increases with age and
      affects 10% of people over 70 years old. Heart failure is characterized by high annual death
      rate reaching 17% and the percentage of rehospitalization at the level of 44% annually. In
      order to reduce morbidity and mortality rates in the case of heart failure, many diagnostic
      and therapeutic methods have been introduced over the last few years, however the prognosis
      for this medical condition is still unfavorable nonetheless.

      Rehospitalizations due to exacerbation of chronic heart failure are an important problem for
      patients suffering from heart failure.

      Rehospitalzations lead to worse prognosis, have an impact on the quality of life and have a
      negative financial impact on the health care system. At the moment, there are numerous
      clinical trials aimed at improving the prognosis of patients with heart failure.

      Levosimendan is a modern drug registered in the treatment of acute heart failure. In the
      current ESC guidelines for the treatment of patients with acute heart failure, levosimendan
      is mainly recommended for the group of patients chronically treated with beta-adrenolytics
      and in the treatment of a peri-infarction shock.

      It is a substance with inotropic positive and vasodilating effects. It belongs to the group
      of drugs sensitizing contractile elements of a myocardium on calcium ions. In the clinical
      trials and meta-analyses, the safety profile of levosimendan is better in comparison to the
      classical pressure amines used in the treatment of acute heart failure: dobutamine and
      dopamine. Beneficial clinical effect of levosimendan is prolonged beyond the period of its
      direct use due to the active metabolites remaining in the bloodstream.

      Currently, studies are being conducted on the efficacy of levosimendan in the prevention of
      heart failure exacerbations. Patients receive levosimendan at repetitive use and preliminary
      results suggest a reduction in the incidence of exacerbations of heart failure. Due to the
      low number of patients included in individual centers and non-homogeneous protocols of the
      use of levosimendan in repeated infusions, the benefits of using this method of treatment can
      not be clearly determined at present. Thanks to the clinical trial planned in the Department
      of Cardiology of the Biziel Hospital with repeatable use of levosimendan, it is possible to
      determine the benefits of this method of treatment more accurately.

      Levosimendan is a drug with a beneficial safety profile, and the most common side effect,
      which is hypotension, will disappear shortly after discontinuation of treatment or after an
      infusion of crystalloids. Patients will be hospitalized at ITK, where a standard physical
      examination will be conducted. The patient will fill in the SF36 questionnaire before the
      treatment to self-evaluate his or hers quality of life. The patient will take medication
      according to the latest outpatient recommendations.

      During the 24-hour treatment, blood pressure will be monitored (until the target dose is
      set). The heart rate will be monitored continuously (for the next 2 hours every 30 minutes,
      then every 1 hour). Daily balance of fluids will be administered.

      The patient will initially receive a standard dose of 0.1 mcg/kgmc/min. In case of good
      tolerance of the drug - the dose will be increased to 0.2 mcg/kgmc/min. If hypotension SBP
      <90 mmHg occurs, the dose will be reduced to 0.05 mcg / kgm / min. If the hypotension
      persists despite the reduction of the drug - the infusion will be terminated and the patient
      will be excluded from the study. The infusion will be terminated within 24 hours, the patient
      will be examined again 4 hours after the end of the infusion, by the attending physician and
      unless there are contraindications - discharged home.

      Patients will be hospitalized every 4 weeks for the next 6 months with the above-mentioned
      parameters from the peripheral blood and march test, before the next dose. The control test
      will also include the determination of the concentration of levosimendan metabolites prior to
      the next infusion.

      During the last follow-up visit, echocardiography and spiroergometry testing will be
      performed before the next dosage.

      After the 12 months of inclusion in the study, a telephone interview will be conducted in the
      direction of rehospitalization due to exacerbation of heart failure.

      The data obtained from the study will be compared with the standard parameters of
      rehospitalization due to the exacerbation of heart failure included in the ESC guidelines.
      The variability of data obtained from the quality of life questionnaire at the beginning and
      at the end of the study will also be evaluated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of rehospitalisations in patients with severe heart failure treated with 24-hour levosimendan infusions
time frame: 12 months
measure: Change in quality of life in patients with severe heart failure treated with 24-hour levosimendan infusions.
time frame: from baseline up to 4 weeks during 6 months
description: via SF-36 questionnaire
measure: Change in sodium in patients with severe heart failure treated with 24-hour: SF-36 questionnaire levosimendan infusions.
time frame: from baseline up to 4 weeks during 6 months
description: counted in mmol/l
measure: Change in kaldyum in patients with severe heart failure treated with 24-hour levosimendan infusions.
time frame: from baseline up to 4 weeks during 6 months
description: counted in mmol/l
measure: Change in NT-proBNP in patients with severe heart failure treated with 24-hour levosimendan infusions.
time frame: from baseline and up to 4 weeks during 6 months.
description: counted in ng/l
measure: Change in troponin T in patients with severe heart failure treated with 24-hour levosimendan infusions.
time frame: from baseline and up to 4 weeks during 6 months.
description: counted in μg/l
arm group label: Levosimendan
arm group type: Experimental
intervention type: Drug
intervention name: Levosimendan
description: The patient will initially receive a standard dose of 0.1 mcg/kgmc/min. In case of good tolerance of the drug - the dose will be increased to 0.2 mcg/kgmc/min. If hypotension SBP <90 mmHg occurs, the dose will be reduced to 0.05 mcg / kgm / min. If the hypotension persists despite the reduction of the drug - the infusion will be terminated and the patient will be excluded from the study. The infusion will be terminated within 24 hours, the patient will be examined again 4 hours after the end of the infusion, by the attending physician and unless there are contraindications - discharged home.
Patients will be hospitalized every 4 weeks for the next 6 months.
arm group label: Levosimendan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Grzegorz Grześk, Professor
role: Principal Investigator
affiliation: Collegium Medicum w Bydgoszczy
last name: Małgorzata Dobosiewicz, PhD
phone: 48602288918
email: margotd@poczta.onet.pl
last name: Wojciech Hertmanowski, MD
phone: 48505518399
email: woj.hertmanowski@gmail.com
facility: 
status: Recruiting
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Collegium Medicum w Bydgoszczy
investigator full name: Małgorzata Dobosiewicz, PhD
investigator title: Professor Grzegorz Grześk
mesh term: Heart Failure
mesh term: Heart Failure, Systolic
mesh term: Systolic Murmurs
mesh term: Simendan
sharing ipd: No