<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/NCT02248532</url>
  </required_header>
  <id_info>
    <org_study_id>REMEDIUM</org_study_id>
    <nct_id>NCT02248532</nct_id>
  </id_info>
  <brief_title>Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy (REMEDIUM)</brief_title>
  <acronym>REMEDIUM</acronym>
  <official_title>Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Centre Ljubljana</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of REMEDIUM project is to develop personalized stem cell therapy for patients with&#xD;
      chronic heart failure due to dilated cardiomyopathy (DCM). The main focus of the project is&#xD;
      (1) on repetitive administration of cell therapy that would allow for long-lasting&#xD;
      improvements in heart function and outcome in this patient population. In parallel, the&#xD;
      investigators aim to (2) develop a standardized patient-specific stem cell product that could&#xD;
      be cryopreserved and stored in a stem cell bank for prolonged time periods, and used for&#xD;
      therapeutic application when clinically indicated. By using a unique multimodality imaging&#xD;
      platform, the goal of this project is also to (3) define standardized clinical criteria that&#xD;
      would serve as a guideline for evaluation of the effects of stem cell therapy in future&#xD;
      clinical trials and everyday clinical settings. Finally, to improve the clinical&#xD;
      implementation of cell therapy,the investigators aim to (4) develop a stem cell delivery&#xD;
      technique that could be used to treat both left and right and ventricular failure and could&#xD;
      be implemented in a standardized fashion designed for a widespread clinical use.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2014</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</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>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in left ventricular ejection fraction</measure>
    <time_frame>baseline and 1 year</time_frame>
    <description>The echocardiography data will be recorded and analyzed at the end of the study by an independent echocardiographer who will be blinded to the patient's treatment status and the timing of the recordings. Left ventricular end-systolic volume and end-diastolic volume and LVEF will be estimated using the Simpson's biplane method and left ventricular end-systolic dimension and end-diastolic dimension will be measured in the parasternal long axis view. All echocardiographic measurements will be averaged for 5 cycles.. The change in left ventricular ejection fraction (LVEF) between randomization and 1 year thereafter will be assessed by 2D echocardiography.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in regional wall motion</measure>
    <time_frame>baseline and 1 year</time_frame>
    <description>Left ventricular segmental wall motion analysis (strain) will be evaluated with TomTec software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany), using a 17-segment model of the left ventricle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular dimension</measure>
    <time_frame>1 year</time_frame>
    <description>The change in left ventricular dimensions between randomization and 1 year thereafter will be assessed by 2D echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in exercise capacity</measure>
    <time_frame>baseline and 1 year</time_frame>
    <description>Change in exercise capacity will be evaluated by 6-minute walk test was performed by a blinded observer according to the standard protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NT-proBNP</measure>
    <time_frame>baseline and 1 year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of ventricular arrhythmias</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac mortality</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Hospitalization for heart failure</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Pump failure mortality</measure>
    <time_frame>1 year</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Dilated Cardiomyopathy</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Repetitive stem cell administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single stem cell administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Stem cell therapy</intervention_name>
    <description>Bone marrow cells will be mobilized into peripheral blood by daily subcutaneous injections of G-CSF (10 µg/kg daily) and collected by leukapheresis. Positive immunomagnetic selection of CD34+ cells will be performed. Electroanatomic mapping of the left ventricle will be performed using the Biosense NOGA system (Biosense-Webster®, Diamond Bar, CA). The target area for cell delivery will be defined as the myocardial segments with unipolar voltage potentials ≥8.3 mV, bipolar amplitudes &gt;1.9 mV, and linear shortening &lt;6%. Intramyocardial delivery of cell suspension will be performed with the MyoStar (BiosenseWebster®, Diamond Bar, CA) injection catheter. Each patient will receive 20 injections (0.3 mL each; total volume of 6 mL). All the procedures will be repeated 6 months after baseline.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70 years old&#xD;
&#xD;
          -  Diagnosis of DCM according to European Society of Cardiology position statement&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) by echocardiography 20-40%,&#xD;
&#xD;
          -  New York Heart Association (NYHA) functional class heart failure II or III for at&#xD;
             least 3 months before referral.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute multi-organ failure&#xD;
&#xD;
          -  History of any malignant disease within 5 years&#xD;
&#xD;
          -  Diminished functional capacity due to non-cardiac co-morbidities (COPD, PAOD, morbid&#xD;
             obesity)&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UMC Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <state>Please Select</state>
        <zip>1000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Slovenia</country>
  </location_countries>
  <reference>
    <citation>Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013 Sep 10;128(11 Suppl 1):S42-9. doi: 10.1161/CIRCULATIONAHA.112.000230.</citation>
    <PMID>24030420</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>January 19, 2018</last_update_submitted>
  <last_update_submitted_qc>January 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Centre Ljubljana</investigator_affiliation>
    <investigator_full_name>Bojan Vrtovec</investigator_full_name>
    <investigator_title>Medical Director, Advanced Heart Failure and Transplantation</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Dilated</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/NCT02248532
org study id: REMEDIUM
nct id: NCT02248532
lead sponsor: 
has dmc: Yes
The goal of REMEDIUM project is to develop personalized stem cell therapy for patients with
      chronic heart failure due to dilated cardiomyopathy (DCM). The main focus of the project is
      (1) on repetitive administration of cell therapy that would allow for long-lasting
      improvements in heart function and outcome in this patient population. In parallel, the
      investigators aim to (2) develop a standardized patient-specific stem cell product that could
      be cryopreserved and stored in a stem cell bank for prolonged time periods, and used for
      therapeutic application when clinically indicated. By using a unique multimodality imaging
      platform, the goal of this project is also to (3) define standardized clinical criteria that
      would serve as a guideline for evaluation of the effects of stem cell therapy in future
      clinical trials and everyday clinical settings. Finally, to improve the clinical
      implementation of cell therapy,the investigators aim to (4) develop a stem cell delivery
      technique that could be used to treat both left and right and ventricular failure and could
      be implemented in a standardized fashion designed for a widespread clinical use.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: Change in left ventricular ejection fraction
time frame: baseline and 1 year
description: The echocardiography data will be recorded and analyzed at the end of the study by an independent echocardiographer who will be blinded to the patient's treatment status and the timing of the recordings. Left ventricular end-systolic volume and end-diastolic volume and LVEF will be estimated using the Simpson's biplane method and left ventricular end-systolic dimension and end-diastolic dimension will be measured in the parasternal long axis view. All echocardiographic measurements will be averaged for 5 cycles.. The change in left ventricular ejection fraction (LVEF) between randomization and 1 year thereafter will be assessed by 2D echocardiography.
measure: Changes in regional wall motion
time frame: baseline and 1 year
description: Left ventricular segmental wall motion analysis (strain) will be evaluated with TomTec software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany), using a 17-segment model of the left ventricle.
measure: Change in left ventricular dimension
time frame: 1 year
description: The change in left ventricular dimensions between randomization and 1 year thereafter will be assessed by 2D echocardiography.
measure: Change in exercise capacity
time frame: baseline and 1 year
description: Change in exercise capacity will be evaluated by 6-minute walk test was performed by a blinded observer according to the standard protocol.
measure: Change in NT-proBNP
time frame: baseline and 1 year
measure: Incidence of ventricular arrhythmias
time frame: 1 year
measure: Cardiac mortality
time frame: 1 year
measure: Hospitalization for heart failure
time frame: 1 year
measure: Pump failure mortality
time frame: 1 year
arm group label: Group A
arm group type: Active Comparator
description: Repetitive stem cell administration
arm group label: Group B
arm group type: Active Comparator
description: Single stem cell administration
intervention type: Biological
intervention name: Stem cell therapy
description: Bone marrow cells will be mobilized into peripheral blood by daily subcutaneous injections of G-CSF (10 µg/kg daily) and collected by leukapheresis. Positive immunomagnetic selection of CD34+ cells will be performed. Electroanatomic mapping of the left ventricle will be performed using the Biosense NOGA system (Biosense-Webster®, Diamond Bar, CA). The target area for cell delivery will be defined as the myocardial segments with unipolar voltage potentials ≥8.3 mV, bipolar amplitudes >1.9 mV, and linear shortening <6%. Intramyocardial delivery of cell suspension will be performed with the MyoStar (BiosenseWebster®, Diamond Bar, CA) injection catheter. Each patient will receive 20 injections (0.3 mL each; total volume of 6 mL). All the procedures will be repeated 6 months after baseline.
arm group label: Group A
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Slovenia
citation: Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013 Sep 10;128(11 Suppl 1):S42-9. doi: 10.1161/CIRCULATIONAHA.112.000230.
PMID: 24030420
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Bojan Vrtovec
investigator title: Medical Director, Advanced Heart Failure and Transplantation
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated