<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/NCT01693042</url>
  </required_header>
  <id_info>
    <org_study_id>2011-01-01REPEAT</org_study_id>
    <secondary_id>2011-000595-33</secondary_id>
    <nct_id>NCT01693042</nct_id>
  </id_info>
  <brief_title>Compare the Effects of Single Versus Repeated Intracoronary Application of Autologous Bone Marrow-derived Mononuclear Cells on Mortality in Patients With Chronic Post-infarction Heart Failure</brief_title>
  <acronym>REPEAT</acronym>
  <official_title>Randomized Controlled Trial to Compare the Effects of Single Versus Repeated Intracoronary Application of Autologous Bone Marrow-derived Mononuclear Cells on Total and SHFM-predicted Mortality in Patients With Chronic Post-infarction Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johann Wolfgang Goethe University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johann Wolfgang Goethe University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Single or repeated application of autologous bone marrow-derived stem cells to treat chronic&#xD;
      post-infarction heart failure&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Improve mortality and morbidity in patients with symptomatic chronic post-infarction heart&#xD;
      failure under full dose conventional medical and device treatment including resynchronization&#xD;
      therapy, by single versus repeated intracoronary infusion of autologous bone marrow-derived&#xD;
      mononuclear cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>November 2013</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">November 2022</primary_completion_date>
  <phase>Phase 2/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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality at 2 years after inclusion into the study</measure>
    <time_frame>2 years</time_frame>
    <description>2-year observed mortality is significantly lower in patients receiving 2 repeated intracoronary applications of autologous bone marrow-derived cells (t2c001) compared to patients receiving 1 intracoronary application of autologous bone marrow-derived cells (t2c001)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Morbidity at 2 and 5 years after inclusion into the study</measure>
    <time_frame>2 years and 5 years</time_frame>
    <description>Efficacy endpoints:&#xD;
Comparison between the 2 treatment groups at 2-year and 5-year follow-up&#xD;
Cardiac mortality, cardiovascular mortality&#xD;
Rehospitalisation for heart failure&#xD;
Ischemic cardiac events (STEMI, NSTEMI, ACS)&#xD;
Coronary revascularisations (PCI / CABG)&#xD;
Heart transplantation, Assist-device implantation&#xD;
New resynchronization therapy, ICD implantation&#xD;
NYHA-Status, NT-proBNP serum levels&#xD;
Minnesota Living with Heart Failure Questionnaire&#xD;
Safety endpoints:&#xD;
bleeding events, all in-hospital events (during hospitalization for BMC therapy), life-threatening arrhythmias, new malignancies</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Single intracoronary cell application</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single intracoronary application of autologous bone marrow derived mononuclear cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>repeated (2 times) intracoronary cell application</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 times (interval 4 months) intracoronary application of autologous bone marrow derived mononuclear cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>intracoronary infusion of autologous bone marrow-derived cells</intervention_name>
    <description>Intracoronary infusion into open vessel / bypass supplying previous (&gt; 3 months) infarct area</description>
    <arm_group_label>Single intracoronary cell application</arm_group_label>
    <arm_group_label>repeated (2 times) intracoronary cell application</arm_group_label>
    <other_name>t2c001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previous myocardial infarction at least 3 months ago, open infarct vessel or bypass&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≤ 45% on echocardiography&#xD;
&#xD;
          -  Stable chronic heart failure NYHA class II to III under constant (4 weeks)&#xD;
             evidence-based optimal medical treatment&#xD;
&#xD;
          -  age 18 - 80 years&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
          -  women of childbearing age: negative pregnancy test; effective contraception for the&#xD;
             first 8 months in the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-ischemic cardiomyopathy&#xD;
&#xD;
          -  Necessity for revascularization in other vessel than the infarct vessel at the time of&#xD;
             study therapy&#xD;
&#xD;
          -  Hemodynamic relevant severe valvular disease with indication for operative /&#xD;
             interventional revision&#xD;
&#xD;
          -  Heart failure with preserved ejection fraction (diastolic heart failure), LVEF &gt; 45%&#xD;
&#xD;
          -  Unstable Angina&#xD;
&#xD;
          -  Severe peripheral artery occlusive disease (≥ Fontaine stadium III)&#xD;
&#xD;
          -  Active infection (C-reactive protein &gt; 10 mg/dl), chronic active hepatitis; any&#xD;
             chronic inflammatory disease, HIV infection&#xD;
&#xD;
          -  Neoplastic disease without documented remission in the last 5 years&#xD;
&#xD;
          -  Stroke ≤ 3 months&#xD;
&#xD;
          -  Impaired renal function (Serum creatinine &gt; 2,5 mg/dl) at the time of study inclusion&#xD;
&#xD;
          -  Relevant liver disease (GOT &gt; 2x upper normal limit, spontaneous INR &gt; 1,5).&#xD;
&#xD;
          -  Diseases of hematopoetic system, anemia (Hemoglobin &lt; 8.5 mg/dl), thrombocytopenia &lt;&#xD;
             100.000/µl)&#xD;
&#xD;
          -  Splenomegaly&#xD;
&#xD;
          -  Allergy or intolerance of clopidogrel, prasugrel, ticagrelor, heparin, bivalirudin&#xD;
&#xD;
          -  History of bleeding disorder&#xD;
&#xD;
          -  gastrointestinal bleeding ≤ 3 months&#xD;
&#xD;
          -  major surgery or trauma ≤ 3 months&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Pregnancy, lactation period&#xD;
&#xD;
          -  mental retardation&#xD;
&#xD;
          -  previous cardiac cell therapy within last 12 months&#xD;
&#xD;
          -  Participation in another clinical trial ≤ 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreas M Zeiher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardiology, Goethe University Frankfurt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Birgit Assmus, MD</last_name>
    <role>Study Director</role>
    <affiliation>Cardiology, Goethe University Frankfurt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zentralklinik Bad Berka</name>
      <address>
        <city>Bad Berka</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goethe University Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Fulda</name>
      <address>
        <city>Fulda</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Mainz</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Hetzelstift</name>
      <address>
        <city>Neustadt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentralklinikum Suhl</name>
      <address>
        <city>Suhl</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>February 25, 2020</last_update_submitted>
  <last_update_submitted_qc>February 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johann Wolfgang Goethe University Hospital</investigator_affiliation>
    <investigator_full_name>A. M. Zeiher</investigator_full_name>
    <investigator_title>Prof. Dr. Andreas M. Zeiher</investigator_title>
  </responsible_party>
  <keyword>heart failure</keyword>
  <keyword>old myocardial infarction</keyword>
  <keyword>bone marrow-derived mononuclear cells</keyword>
  <keyword>chronic</keyword>
  <keyword>ischemic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Infarction</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/NCT01693042
org study id: 2011-01-01REPEAT
secondary id: 2011-000595-33
nct id: NCT01693042
lead sponsor: 
has dmc: Yes
Single or repeated application of autologous bone marrow-derived stem cells to treat chronic
      post-infarction heart failure
Improve mortality and morbidity in patients with symptomatic chronic post-infarction heart
      failure under full dose conventional medical and device treatment including resynchronization
      therapy, by single versus repeated intracoronary infusion of autologous bone marrow-derived
      mononuclear cells.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mortality at 2 years after inclusion into the study
time frame: 2 years
description: 2-year observed mortality is significantly lower in patients receiving 2 repeated intracoronary applications of autologous bone marrow-derived cells (t2c001) compared to patients receiving 1 intracoronary application of autologous bone marrow-derived cells (t2c001)
measure: Morbidity at 2 and 5 years after inclusion into the study
time frame: 2 years and 5 years
description: Efficacy endpoints:
Comparison between the 2 treatment groups at 2-year and 5-year follow-up
Cardiac mortality, cardiovascular mortality
Rehospitalisation for heart failure
Ischemic cardiac events (STEMI, NSTEMI, ACS)
Coronary revascularisations (PCI / CABG)
Heart transplantation, Assist-device implantation
New resynchronization therapy, ICD implantation
NYHA-Status, NT-proBNP serum levels
Minnesota Living with Heart Failure Questionnaire
Safety endpoints:
bleeding events, all in-hospital events (during hospitalization for BMC therapy), life-threatening arrhythmias, new malignancies
arm group label: Single intracoronary cell application
arm group type: Active Comparator
description: Single intracoronary application of autologous bone marrow derived mononuclear cells
arm group label: repeated (2 times) intracoronary cell application
arm group type: Active Comparator
description: 2 times (interval 4 months) intracoronary application of autologous bone marrow derived mononuclear cells
intervention type: Biological
intervention name: intracoronary infusion of autologous bone marrow-derived cells
description: Intracoronary infusion into open vessel / bypass supplying previous (> 3 months) infarct area
arm group label: Single intracoronary cell application
arm group label: repeated (2 times) intracoronary cell application
other name: t2c001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Andreas M Zeiher, MD
role: Principal Investigator
affiliation: Cardiology, Goethe University Frankfurt
last name: Birgit Assmus, MD
role: Study Director
affiliation: Cardiology, Goethe University Frankfurt
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Johann Wolfgang Goethe University Hospital
investigator full name: A. M. Zeiher
investigator title: Prof. Dr. Andreas M. Zeiher
mesh term: Heart Failure
mesh term: Infarction