<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/NCT03022877</url>
  </required_header>
  <id_info>
    <org_study_id>Levo-STEMI</org_study_id>
    <nct_id>NCT03022877</nct_id>
  </id_info>
  <brief_title>Acute and Chronic Protective Effects of Peri-interventional Administration of Levosimendan in ST Elevation Myocardial Infarctions</brief_title>
  <official_title>Acute and Chronic Protective Effects of Peri-interventional Administration of Levosimendan in ST Elevation Myocardial Infarctions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RWTH Aachen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RWTH Aachen University</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>
      In the proposed project the investigators want to assess whether the approach of the&#xD;
      post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can&#xD;
      be used with a positive influence on the outcomes with respect to myocardial damage, cardiac&#xD;
      left ventricular remodeling, myocardial function, the occurrence of cardiac events and&#xD;
      quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An acute ST-elevation myocardial infarction (STEMI) is a severe disease that triggers an&#xD;
      adverse remodeling, and served in progressive heart failure with a case fatality rate of 50%&#xD;
      in 5 years. The opening of the occluded vessel is the first and most important therapy, the&#xD;
      reperfusion improved both the function as well as the long-term survival. At the same time,&#xD;
      experimental and clinical studies show, however, that this reperfusion self-reinforced damage&#xD;
      of the myocardium. An additional Intervention in this trigger phase could not only reduce the&#xD;
      acute damage, but long-term protective effects. Both effects could be an approach for the&#xD;
      Calcium-Sensitizer Levosimendan in the animal model. So far, no clear effect on the&#xD;
      remodeling and survive was demonstrated after myocardial infarction in the clinic. This could&#xD;
      be mainly due to the delayed application in relation to the reperfusion and on the selection&#xD;
      of suitable methods for the presentation of the effects on myocardial structure and function.&#xD;
      In the proposed project the investigators want to assess whether the approach of the&#xD;
      post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can&#xD;
      be used with a positive influence on the outcomes with respect to myocardial damage, cardiac&#xD;
      left ventricular remodeling, myocardial function, the occurrence of cardiac events and&#xD;
      quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Rationale obsolete&#xD;
  </why_stopped>
  <start_date type="Anticipated">June 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of the increase in left ventricular end-diastolic volume index (LVEDVi)</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>echocardiography and MRI examinations (LVEDVi) and comparison between baseline and 12 months data</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Size of the acute myocardial damage due to the infarction</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>MRI examination (infarction area) and comparison between baseline and 12 months data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>collection of data from the patient after 12 months about adverse events as myocardial infarction, stroke, revascularization and death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>functional changes (imaging)</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>echocardiography and MRI examinations about LV function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>structural changes</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>MRI examinations about fibrosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>functional changes (spirometry)</measure>
    <time_frame>12 months after coronary intervention due to the infarction</time_frame>
    <description>changes of capacity by spirometry.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Myocardial Infarction</condition>
  <condition>Outcome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo is given as a Bolus (instead of Bolus application of Levosimendan) over 10 min i.v., starting 10 min before recanalization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bolus Levosimendan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bolus and infusion Levosimendan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization and additionally as continuous infusion (0.1-0.2 µg/kg/min i. v. for 24 hours).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levosimendan</intervention_name>
    <description>In a prospective randomized setting, patients are included with an acute STEMI of the anterior wall. A bolus administration Levosimendan with/without following continuous infusion over 24 hours compared to a control group (placebo) will be examined. The initiation of therapy is carried out for 10 min. prior to reperfusion. The coronary Intervention is performed immediately after inclusion at the latest within 6 hours after the onset of symptoms. The administration of Levosimendan is based on a fixed schema: Bolus: 12 µg/kg over 10 min I. V., starting 10 min before recanalization and an addition of 0.1-0.2 µg/kg/min i. v. for 24 hours in the continuous infusion group.</description>
    <arm_group_label>Bolus Levosimendan</arm_group_label>
    <arm_group_label>Bolus and infusion Levosimendan</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  STEMI of the anterior wall &lt; 6 hrs&#xD;
&#xD;
          -  capacity to Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous myocardial infarction or bypass surgery&#xD;
&#xD;
          -  relevant vitium&#xD;
&#xD;
          -  STEMI of the posterior wall&#xD;
&#xD;
          -  any contraindications to MRI&#xD;
&#xD;
          -  unstable hemodynamics (hypotension, catecholamine therapy, severe arrhythmia),&#xD;
             -respiratory failure&#xD;
&#xD;
          -  onset of symptoms more than 6 hours.&#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>Michael Becker</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardiology, RWTH University Hospital Aachen</affiliation>
  </overall_official>
  <reference>
    <citation>Brooks GC, Lee BK, Rao R, Lin F, Morin DP, Zweibel SL, Buxton AE, Pletcher MJ, Vittinghoff E, Olgin JE; PREDICTS Investigators. Predicting Persistent Left Ventricular Dysfunction Following Myocardial Infarction: The PREDICTS Study. J Am Coll Cardiol. 2016 Mar 15;67(10):1186-1196. doi: 10.1016/j.jacc.2015.12.042.</citation>
    <PMID>26965540</PMID>
  </reference>
  <results_reference>
    <citation>Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation. 2001 Dec 18;104(25):3158-67. doi: 10.1161/hc5001.100039.</citation>
    <PMID>11748117</PMID>
  </results_reference>
  <results_reference>
    <citation>Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.</citation>
    <PMID>17855673</PMID>
  </results_reference>
  <results_reference>
    <citation>du Toit EF, Smith W, Muller C, Strijdom H, Stouthammer B, Woodiwiss AJ, Norton GR, Lochner A. Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity. Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2336-43. doi: 10.1152/ajpheart.00481.2007. Epub 2008 Mar 21.</citation>
    <PMID>18359896</PMID>
  </results_reference>
  <results_reference>
    <citation>Hein M, Roehl AB, Baumert JH, Scherer K, Steendijk P, Rossaint R. Anti-ischemic effects of inotropic agents in experimental right ventricular infarction. Acta Anaesthesiol Scand. 2009 Aug;53(7):941-8. doi: 10.1111/j.1399-6576.2009.01994.x. Epub 2009 May 6.</citation>
    <PMID>19426242</PMID>
  </results_reference>
  <results_reference>
    <citation>Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004 Apr 1;62(1):74-85. doi: 10.1016/j.cardiores.2004.01.006.</citation>
    <PMID>15023554</PMID>
  </results_reference>
  <results_reference>
    <citation>Qarawani D, Cohen A, Nahir M, Hasin Y. Facilitation of left ventricular function recovery post percutaneous coronary intervention by levosimendan. Int J Cardiol. 2013 Sep 20;168(1):237-42. doi: 10.1016/j.ijcard.2012.09.088. Epub 2012 Oct 11.</citation>
    <PMID>23063476</PMID>
  </results_reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>October 25, 2022</last_update_submitted>
  <last_update_submitted_qc>October 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>ST Elevation Myocardial Infarction</mesh_term>
    <mesh_term>Infarction</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/NCT03022877
org study id: Levo-STEMI
nct id: NCT03022877
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In the proposed project the investigators want to assess whether the approach of the
      post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can
      be used with a positive influence on the outcomes with respect to myocardial damage, cardiac
      left ventricular remodeling, myocardial function, the occurrence of cardiac events and
      quality of life.
An acute ST-elevation myocardial infarction (STEMI) is a severe disease that triggers an
      adverse remodeling, and served in progressive heart failure with a case fatality rate of 50%
      in 5 years. The opening of the occluded vessel is the first and most important therapy, the
      reperfusion improved both the function as well as the long-term survival. At the same time,
      experimental and clinical studies show, however, that this reperfusion self-reinforced damage
      of the myocardium. An additional Intervention in this trigger phase could not only reduce the
      acute damage, but long-term protective effects. Both effects could be an approach for the
      Calcium-Sensitizer Levosimendan in the animal model. So far, no clear effect on the
      remodeling and survive was demonstrated after myocardial infarction in the clinic. This could
      be mainly due to the delayed application in relation to the reperfusion and on the selection
      of suitable methods for the presentation of the effects on myocardial structure and function.
      In the proposed project the investigators want to assess whether the approach of the
      post-conditioning by Levosimendan in patients with acute STEMI is safe and reproducible, can
      be used with a positive influence on the outcomes with respect to myocardial damage, cardiac
      left ventricular remodeling, myocardial function, the occurrence of cardiac events and
      quality of life.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Reduction of the increase in left ventricular end-diastolic volume index (LVEDVi)
time frame: 12 months after coronary intervention due to the infarction
description: echocardiography and MRI examinations (LVEDVi) and comparison between baseline and 12 months data
measure: Size of the acute myocardial damage due to the infarction
time frame: 12 months after coronary intervention due to the infarction
description: MRI examination (infarction area) and comparison between baseline and 12 months data
measure: Event-free survival
time frame: 12 months after coronary intervention due to the infarction
description: collection of data from the patient after 12 months about adverse events as myocardial infarction, stroke, revascularization and death
measure: functional changes (imaging)
time frame: 12 months after coronary intervention due to the infarction
description: echocardiography and MRI examinations about LV function
measure: structural changes
time frame: 12 months after coronary intervention due to the infarction
description: MRI examinations about fibrosis
measure: functional changes (spirometry)
time frame: 12 months after coronary intervention due to the infarction
description: changes of capacity by spirometry.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo is given as a Bolus (instead of Bolus application of Levosimendan) over 10 min i.v., starting 10 min before recanalization.
arm group label: Bolus Levosimendan
arm group type: Active Comparator
description: Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization.
arm group label: Bolus and infusion Levosimendan
arm group type: Active Comparator
description: Levosimendan is given as Bolus (12 µg/kg over 10 min i.v.), starting 10 min before recanalization and additionally as continuous infusion (0.1-0.2 µg/kg/min i. v. for 24 hours).
intervention type: Drug
intervention name: Levosimendan
description: In a prospective randomized setting, patients are included with an acute STEMI of the anterior wall. A bolus administration Levosimendan with/without following continuous infusion over 24 hours compared to a control group (placebo) will be examined. The initiation of therapy is carried out for 10 min. prior to reperfusion. The coronary Intervention is performed immediately after inclusion at the latest within 6 hours after the onset of symptoms. The administration of Levosimendan is based on a fixed schema: Bolus: 12 µg/kg over 10 min I. V., starting 10 min before recanalization and an addition of 0.1-0.2 µg/kg/min i. v. for 24 hours in the continuous infusion group.
arm group label: Bolus Levosimendan
arm group label: Bolus and infusion Levosimendan
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Becker
role: Principal Investigator
affiliation: Cardiology, RWTH University Hospital Aachen
citation: Brooks GC, Lee BK, Rao R, Lin F, Morin DP, Zweibel SL, Buxton AE, Pletcher MJ, Vittinghoff E, Olgin JE; PREDICTS Investigators. Predicting Persistent Left Ventricular Dysfunction Following Myocardial Infarction: The PREDICTS Study. J Am Coll Cardiol. 2016 Mar 15;67(10):1186-1196. doi: 10.1016/j.jacc.2015.12.042.
PMID: 26965540
citation: Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation. 2001 Dec 18;104(25):3158-67. doi: 10.1161/hc5001.100039.
PMID: 11748117
citation: Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.
PMID: 17855673
citation: du Toit EF, Smith W, Muller C, Strijdom H, Stouthammer B, Woodiwiss AJ, Norton GR, Lochner A. Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity. Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2336-43. doi: 10.1152/ajpheart.00481.2007. Epub 2008 Mar 21.
PMID: 18359896
citation: Hein M, Roehl AB, Baumert JH, Scherer K, Steendijk P, Rossaint R. Anti-ischemic effects of inotropic agents in experimental right ventricular infarction. Acta Anaesthesiol Scand. 2009 Aug;53(7):941-8. doi: 10.1111/j.1399-6576.2009.01994.x. Epub 2009 May 6.
PMID: 19426242
citation: Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004 Apr 1;62(1):74-85. doi: 10.1016/j.cardiores.2004.01.006.
PMID: 15023554
citation: Qarawani D, Cohen A, Nahir M, Hasin Y. Facilitation of left ventricular function recovery post percutaneous coronary intervention by levosimendan. Int J Cardiol. 2013 Sep 20;168(1):237-42. doi: 10.1016/j.ijcard.2012.09.088. Epub 2012 Oct 11.
PMID: 23063476
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: ST Elevation Myocardial Infarction
mesh term: Infarction
mesh term: Simendan
sharing ipd: No