xml: <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/NCT06021587</url>
    </required_header>
    <id_info>
      <org_study_id>2023_PI_084</org_study_id>
      <nct_id>NCT06021587</nct_id>
    </id_info>
    <brief_title>Interest of Levosimendan Preconditioning for Cardiac Surgery Under CEC in Heart Failure Patients With Impaired Ejection Fraction</brief_title>
    <acronym>LevoCV</acronym>
    <official_title>Interest of Levosimendan Preconditioning for Cardiac Surgery Under CEC in Heart Failure Patients With Impaired Ejection Fraction</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Central Hospital, Nancy, France</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Central Hospital, Nancy, France</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>
        Levosimendan, a drug with inotropic, vasodilatory and myocardial protective properties, has&#xD;
        been proposed for the prevention and treatment of postoperative low cardiac output syndrome&#xD;
        in cardiac surgery. Despite preliminary studies with promising results, large randomized&#xD;
        controlled trials aimed at demonstrating the benefits of levosimendan did not show&#xD;
        superiority over placebo in this indication. However, in these studies, the infusion was&#xD;
        neither performed at the maximum dosage nor during the 24 hours preceding the surgery, but&#xD;
        mainly at the very beginning of the operation. However, post hoc analyses showed a reduction&#xD;
        in mortality and in the occurrence of low cardiac output syndrome in the subgroup of patients&#xD;
        who had undergone isolated coronary artery bypass grafting, in contrast to those who had&#xD;
        undergone valvular or combined surgery. Another recent study suggests that under similar&#xD;
        conditions, preconditioning with levosimendan started 48 hours before surgery reduces the&#xD;
        length of stay in intensive care and the average cost of hospitalization. There are no formal&#xD;
        recommendations on the prophylactic use of levosimendan in cardiac surgery for heart failure&#xD;
        patients with impaired LVAS. However, the France-Levo registry, a multicenter observational&#xD;
        study requested by the HAS, has shown that in real practice there is a place for&#xD;
        preconditioning with levosimendan, which is used in this indication for 7% of the patients in&#xD;
        the registry. The Cardiovascular Surgery and Transplantation Department of the Nancy Brabois&#xD;
        University Hospital, which actively participated in the France-Levo registry, is one of the&#xD;
        cardiac surgery centers that uses this practice, as is the University Hospital of Rouen. It&#xD;
        is interesting to be able to evaluate retrospectively whether levosimendan preconditioning&#xD;
        has a positive impact on the postoperative prognosis of patients and more particularly on the&#xD;
        reduction of the length of stay in critical care and in hospital compared to standard&#xD;
        management.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 1, 2023</start_date>
    <completion_date type="Anticipated">October 10, 2023</completion_date>
    <primary_completion_date type="Actual">July 2, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Major Adverse Cardiac Events (MACE) criteria at 30 days</measure>
      <time_frame>30 days after Levosimendan exposure</time_frame>
      <description>to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery with extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of cardiovascular events at 30 days post-op.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>major renal events (MAKE) at 30 days from the date of surgery</measure>
      <time_frame>30 days after Levosimendan exposure</time_frame>
      <description>to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery under extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of renal events at 30 days post cardiac surgery.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>On 1-year mortality</measure>
      <time_frame>1 year after Levosimendan exposure</time_frame>
      <description>To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular dysfunction on 1-year mortality</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of stay in ICU</measure>
      <time_frame>date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months</time_frame>
      <description>To evaluate the impact of levosimendan preconditioning preoperatively for cardiac surgery on critical care length of stay in patients with heart failure with impaired preoperative LVAS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>the total length of hospital stay</measure>
      <time_frame>start date of hospitalization in intensive care to the date of discharge from conventional sectors evaluated up to 3 months</time_frame>
      <description>To evaluate the impact of preconditioning with Levosimendan preoperatively for cardiac surgery in patients with heart failure with impaired preoperative left ventricular dysfunction on the total length of hospital stay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of left ventricular ejection fraction by cardiac ultrasound at hospital discharge</measure>
      <time_frame>date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months</time_frame>
      <description>To evaluate the impact of Levosimendan preconditioning before cardiac surgery in patients with heart failure and impaired on left ventricular systolic function (measured by cardiac ultrasound) at hospital discharge</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>duration of catecholamine use after surgery</measure>
      <time_frame>date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months</time_frame>
      <description>To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular function before surgery on the duration of catecholamine use after surgery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia using the score Vasoactive Inotropic Score (VIS)</measure>
      <time_frame>date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months</time_frame>
      <description>To evaluate the impact of preconditioning with Levosimendan in preoperative cardiac surgery in patients with heart failure with impaired preoperative LVAS on the severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia. High VIS was empirically defined as ≥ 20. Maximum VIS≥20 predicts an increased likelihood of a poor composite clinical outcome</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Levosimendan</condition>
    <condition>Cardiac Surgery</condition>
    <condition>Heart Failure With Reduced Ejection Fraction</condition>
    <arm_group>
      <arm_group_label>Levosimendan</arm_group_label>
      <description>Major patients in heart failure with impaired LVEF (&lt; 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at different French Hospital, and who have received Levosimendan preoperatively</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control - No Levosimendan</arm_group_label>
      <description>Major patients in heart failure with impaired LVEF (&lt; 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at different French Hospital and who have not received Levosimendan preoperatively</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Levosimendan</intervention_name>
      <description>Initiation of levosimendan 48 hours before surgery</description>
      <arm_group_label>Levosimendan</arm_group_label>
      <other_name>Interventional</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>No Levosimendan</intervention_name>
      <description>Without Levosimendan Infusion</description>
      <arm_group_label>Control - No Levosimendan</arm_group_label>
      <other_name>Control</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Preoperative heart failure patients with impaired LVEF who underwent left heart surgery&#xD;
          (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under&#xD;
          extracorporeal circulation from 01/09/2018 to 28/02/2022 at different University Hospital&#xD;
          in France&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with heart failure impaired LVEF (&lt; 40%), who have undergone left heart&#xD;
               surgery (coronary artery bypass grafting and/or mitral and/or aortic valve&#xD;
               replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at&#xD;
               different University Hospital in France&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Initiation of levosimendan &gt; 48 hours or &lt; 24 hours before surgery ECMO pre- or&#xD;
               post-op&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Thomas KLEIN, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Central Hospital, Nancy, France</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Thomas KLEIN, MD</last_name>
      <phone>+3383154045</phone>
      <email>t.klein@chru-nancy.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Thomas KLEIN, MD</last_name>
      <phone>++33154045</phone>
      <email>t.klein@chru-nancy.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>'CHRU Nancy</name>
        <address>
          <city>Vandœuvre-lès-Nancy</city>
          <state>Meurthe Et Moselle</state>
          <zip>54530</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>KLEIN Thomas, MD</last_name>
        <phone>+33383154045</phone>
        <email>t.klein@chru-nancy.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Central Hospital, Nancy, France</investigator_affiliation>
      <investigator_full_name>Klein Thomas</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Levosimendan</keyword>
    <keyword>Cardiac Surgery</keyword>
    <keyword>Cardiopulmonary Bypass</keyword>
    <keyword>Heart Failure With Reduced Ejection Fraction</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Heart Failure</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>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06021587
  org study id: 2023_PI_084
  nct id: NCT06021587
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Levosimendan, a drug with inotropic, vasodilatory and myocardial protective properties, has
        been proposed for the prevention and treatment of postoperative low cardiac output syndrome
        in cardiac surgery. Despite preliminary studies with promising results, large randomized
        controlled trials aimed at demonstrating the benefits of levosimendan did not show
        superiority over placebo in this indication. However, in these studies, the infusion was
        neither performed at the maximum dosage nor during the 24 hours preceding the surgery, but
        mainly at the very beginning of the operation. However, post hoc analyses showed a reduction
        in mortality and in the occurrence of low cardiac output syndrome in the subgroup of patients
        who had undergone isolated coronary artery bypass grafting, in contrast to those who had
        undergone valvular or combined surgery. Another recent study suggests that under similar
        conditions, preconditioning with levosimendan started 48 hours before surgery reduces the
        length of stay in intensive care and the average cost of hospitalization. There are no formal
        recommendations on the prophylactic use of levosimendan in cardiac surgery for heart failure
        patients with impaired LVAS. However, the France-Levo registry, a multicenter observational
        study requested by the HAS, has shown that in real practice there is a place for
        preconditioning with levosimendan, which is used in this indication for 7% of the patients in
        the registry. The Cardiovascular Surgery and Transplantation Department of the Nancy Brabois
        University Hospital, which actively participated in the France-Levo registry, is one of the
        cardiac surgery centers that uses this practice, as is the University Hospital of Rouen. It
        is interesting to be able to evaluate retrospectively whether levosimendan preconditioning
        has a positive impact on the postoperative prognosis of patients and more particularly on the
        reduction of the length of stay in critical care and in hospital compared to standard
        management.
  observational model: Case-Control
  time perspective: Retrospective
  measure: Major Adverse Cardiac Events (MACE) criteria at 30 days
  time frame: 30 days after Levosimendan exposure
  description: to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery with extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of cardiovascular events at 30 days post-op.
  measure: major renal events (MAKE) at 30 days from the date of surgery
  time frame: 30 days after Levosimendan exposure
  description: to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery under extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of renal events at 30 days post cardiac surgery.
  measure: On 1-year mortality
  time frame: 1 year after Levosimendan exposure
  description: To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular dysfunction on 1-year mortality
  measure: Length of stay in ICU
  time frame: date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
  description: To evaluate the impact of levosimendan preconditioning preoperatively for cardiac surgery on critical care length of stay in patients with heart failure with impaired preoperative LVAS
  measure: the total length of hospital stay
  time frame: start date of hospitalization in intensive care to the date of discharge from conventional sectors evaluated up to 3 months
  description: To evaluate the impact of preconditioning with Levosimendan preoperatively for cardiac surgery in patients with heart failure with impaired preoperative left ventricular dysfunction on the total length of hospital stay
  measure: Measurement of left ventricular ejection fraction by cardiac ultrasound at hospital discharge
  time frame: date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
  description: To evaluate the impact of Levosimendan preconditioning before cardiac surgery in patients with heart failure and impaired on left ventricular systolic function (measured by cardiac ultrasound) at hospital discharge
  measure: duration of catecholamine use after surgery
  time frame: date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
  description: To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular function before surgery on the duration of catecholamine use after surgery
  measure: severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia using the score Vasoactive Inotropic Score (VIS)
  time frame: date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
  description: To evaluate the impact of preconditioning with Levosimendan in preoperative cardiac surgery in patients with heart failure with impaired preoperative LVAS on the severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia. High VIS was empirically defined as ≥ 20. Maximum VIS≥20 predicts an increased likelihood of a poor composite clinical outcome
  arm group label: Levosimendan
  description: Major patients in heart failure with impaired LVEF (< 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at different French Hospital, and who have received Levosimendan preoperatively
  arm group label: Control - No Levosimendan
  description: Major patients in heart failure with impaired LVEF (< 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at different French Hospital and who have not received Levosimendan preoperatively
  intervention type: Drug
  intervention name: Levosimendan
  description: Initiation of levosimendan 48 hours before surgery
  arm group label: Levosimendan
  other name: Interventional
  intervention type: Drug
  intervention name: No Levosimendan
  description: Without Levosimendan Infusion
  arm group label: Control - No Levosimendan
  other name: Control
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  last name: Thomas KLEIN, MD
  role: Principal Investigator
  affiliation: Central Hospital, Nancy, France
  last name: Thomas KLEIN, MD
  phone: +3383154045
  email: t.klein@chru-nancy.fr
  last name: Thomas KLEIN, MD
  phone: ++33154045
  email: t.klein@chru-nancy.fr
  facility: 
  status: Recruiting
  contact: 
  country: France
  responsible party type: Principal Investigator
  investigator affiliation: Central Hospital, Nancy, France
  investigator full name: Klein Thomas
  investigator title: Principal Investigator
  mesh term: Heart Failure
  mesh term: Simendan
  sharing ipd: Undecided