<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/NCT03798353</url>
  </required_header>
  <id_info>
    <org_study_id>ICOR-2016-02</org_study_id>
    <secondary_id>2018-001964-49</secondary_id>
    <nct_id>NCT03798353</nct_id>
  </id_info>
  <brief_title>Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue</brief_title>
  <acronym>PERISCOPE</acronym>
  <official_title>Pericardial Matrix With Mesenchymal Stem Cells for the Treatment of Patients With Infarcted Myocardial Tissue (The PERISCOPE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundació Institut Germans Trias i Pujol</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Germans Trias i Pujol Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundació Institut Germans Trias i Pujol</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function.&#xD;
      Today, there are treatments such as primary angioplasty and thrombolysis that are effective&#xD;
      in limiting cell death after acute myocardial infarction. However, the post-infarct scar&#xD;
      often conditions a global ventricular remodeling that can evolve clinically towards heart&#xD;
      failure and in more advanced stages the only therapy that completely restores cardiac&#xD;
      function is heart transplantation.&#xD;
&#xD;
      Mesenchymal stem cells are multipotent cells found from embryonic mesoderm and found in all&#xD;
      tissues. In the field of cardiac regeneration, studies have shown a certain degree of benefit&#xD;
      when treated with MSCs from different origins. Our approach is based on a decellularized&#xD;
      matrix that carries the cells directly over myocardial infarction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today&#xD;
      there are treatments such as primary angioplasty and thrombolysis that are effective in&#xD;
      limiting cell death after acute myocardial infarction. However, the post-infarct scar often&#xD;
      conditions a global ventricular remodeling that can evolve clinically towards heart failure&#xD;
      and, in more advanced stages, the only therapy that completely restores cardiac function is&#xD;
      heart transplantation.&#xD;
&#xD;
      Experimental studies are evaluating new therapeutic approaches based on tissue engineering&#xD;
      for myocardial regeneration. Cardiac tissue engineering attempts to create functional tissue&#xD;
      constructs that can restore the structure and function of damaged myocardium.&#xD;
&#xD;
      Mesenchymal stem cells (MSCs) are multipotent cells that develop from embryonic mesoderm and&#xD;
      are found in all structural tissues of the body.&#xD;
&#xD;
      In the field of cardiac regeneration, studies have shown a certain degree of benefit when&#xD;
      treated with MSCs from different origins. The investigators approach is based on a&#xD;
      decellularized matrix that carries the cells directly over myocardial infarction.&#xD;
&#xD;
      Among the different types of MSC currently available, the investigators propose the use of&#xD;
      those derived from the connective tissue surrounding the great vessels (2 arteries and one&#xD;
      vein) of the umbilical cord called Wharton's gelatin (MSC, WJ) whose immunomodulatory&#xD;
      properties are described extensively in the literature. These MSC, WJ cells have a PEI&#xD;
      approved by the Spanish Agency for Medicines and Healthcare Products (AEMPS) (PEI 16-017)&#xD;
      that guarantees an optimal manufacturing process for a clinical trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 13, 2019</start_date>
  <completion_date type="Actual">October 6, 2022</completion_date>
  <primary_completion_date type="Actual">September 27, 2022</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>- Experimental group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.&#xD;
In addition, the matrix-cell construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue.&#xD;
- Control group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The randomization will be known exclusively by the cardiac surgery team and the study coordinator, and it will be blind to the patient and to the rest of the investigators team: clinical cardiologist who performs the follow-up, team that performs image tests, core lab that evaluates the imaging tests and the equipment that statistically analyzes the data.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.</measure>
    <time_frame>at 12 months of follow-up</time_frame>
    <description>Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.</measure>
    <time_frame>At 1 week, 3 and 6 months</time_frame>
    <description>Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death rate or rehospitalization due to cardiovascular causes</measure>
    <time_frame>At 1 week, 3 , 6and 12 months</time_frame>
    <description>Death rate or rehospitalization due to cardiovascular causes at week, 3, 6 and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of relevant arrhythmias in Holter of 24 hours</measure>
    <time_frame>At 1 week, 3 and 12 months</time_frame>
    <description>Rate of relevant arrhythmias in Holter of 24 hours a week, 3 and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relevant changes in N-terminal B-type natriuretic peptide (NT-proBNP) and High sensitivity troponin I (hsTnI) levels</measure>
    <time_frame>At 1 week, 3 and 12 months</time_frame>
    <description>Relevant changes in NT-proBNP and hsTnI levels at week, 3 and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the necrotic myocardial mass ratio</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>Changes in the necrotic myocardial mass ratio due to gadolinium retention at 3 and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of regional contractility</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>change of regional contractility by nuclear magnetic resonance (NMR) at 3 and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ejection fraction of the left ventricle</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>Changes in ejection fraction of the left at 3 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in left and right ventricular geometric remodeling</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>changes in left and right ventricular geometric remodeling at 3 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the score on the quality of life test Short Form 36 Healthy Survey (SF-36).</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>Changes in the score on the quality of life test SF-36 will be used at 3 and 12 months. The mínimum value is 0 and the máximum value is 100. Higher scores mean a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the score on the quality of life Kansas City Cardiomyopathy Questionnaire (KCCQ) test in cases of participants with heart failure will be used.</measure>
    <time_frame>At 3 and 12 months</time_frame>
    <description>Changes in the score on the quality of life test KCCQ in cases of participants with heart failure will be used at 3 and 12 months. The test is composed of 23 items. The options for the answers are Likert scales of 1 to 5, 6 or 7 points and the score of each of its dimensions has a theoretical range from 0 to 100, 100 being the best outcome.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>monocyte populations and cytokines and chemokines levels</measure>
    <time_frame>At screening, day 3 and day 5</time_frame>
    <description>changes in the monocyte populations and cytokines and chemokines levels between the two groups in order to analyze if the PeriCord could improve these variables</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.&#xD;
In addition, the matrix-cell (PeriCord) construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue.&#xD;
PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.</intervention_name>
    <description>A matrix-cell construct (PeriCord) will be placed on the ischemic area of the non-candidate revascularization area during a surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.</description>
    <arm_group_label>Experimental group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery by sternotomy</intervention_name>
    <description>The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed only the by-pass.</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Myocardial infarction of ≥50% of transmurally due to MR&#xD;
&#xD;
          -  Candidate for coronary by-pass through that or another territory&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Signature of informed consent&#xD;
&#xD;
          -  Wave Q present in the ECG&#xD;
&#xD;
          -  Followed by the cardiology service of Germans Trial i Pujol hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe valvular disease with indication of surgical repair&#xD;
&#xD;
          -  Candidate for ventricular remodeling&#xD;
&#xD;
          -  Contraindication for MR (creatinine clearance less than 30 ml / min / 1.73m2, metallic&#xD;
             implant carriers, claustrophobia)&#xD;
&#xD;
          -  Extracardiac disease with estimated life expectancy less than 1 year&#xD;
&#xD;
          -  Neoplastic disease detected in the last five years or without complete remission&#xD;
&#xD;
          -  Severe renal or hepatic insufficiency&#xD;
&#xD;
          -  Abnormal laboratory values, not explainable at the time of inclusion, and that at the&#xD;
             discretion of the investigator contraindicate the patient's participation in the study&#xD;
&#xD;
          -  Patients with a previous cardiac intervention&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding.&#xD;
&#xD;
          -  Women of childbearing age who are heterosexually active and who do not use an&#xD;
             effective contraceptive method from 14 days before the inclusion in the study and at&#xD;
             least up to 12 weeks after the end of the study.&#xD;
&#xD;
          -  Simultaneous participation in another clinical trial or treatment with another product&#xD;
             in investigational phase in the 30 days prior to inclusion in the study.&#xD;
&#xD;
          -  Negation of the patient to be followed by a period that exceeds the clinical trial&#xD;
             itself (long-term follow-up in the second and third year).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antoni Bayes-Genís, MD, PhD,FESC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut del Cor, HUGTiP, IGTP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiac repair</keyword>
  <keyword>Wharton jelly mesenchymal stem cells</keyword>
  <keyword>Chronic myocardial infarction</keyword>
  <keyword>Tissue engineering</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>Clinical trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</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/NCT03798353
org study id: ICOR-2016-02
secondary id: 2018-001964-49
nct id: NCT03798353
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function.
      Today, there are treatments such as primary angioplasty and thrombolysis that are effective
      in limiting cell death after acute myocardial infarction. However, the post-infarct scar
      often conditions a global ventricular remodeling that can evolve clinically towards heart
      failure and in more advanced stages the only therapy that completely restores cardiac
      function is heart transplantation.

      Mesenchymal stem cells are multipotent cells found from embryonic mesoderm and found in all
      tissues. In the field of cardiac regeneration, studies have shown a certain degree of benefit
      when treated with MSCs from different origins. Our approach is based on a decellularized
      matrix that carries the cells directly over myocardial infarction.
Myocardial infarction causes necrosis of myocardial cells and reduces cardiac function. Today
      there are treatments such as primary angioplasty and thrombolysis that are effective in
      limiting cell death after acute myocardial infarction. However, the post-infarct scar often
      conditions a global ventricular remodeling that can evolve clinically towards heart failure
      and, in more advanced stages, the only therapy that completely restores cardiac function is
      heart transplantation.

      Experimental studies are evaluating new therapeutic approaches based on tissue engineering
      for myocardial regeneration. Cardiac tissue engineering attempts to create functional tissue
      constructs that can restore the structure and function of damaged myocardium.

      Mesenchymal stem cells (MSCs) are multipotent cells that develop from embryonic mesoderm and
      are found in all structural tissues of the body.

      In the field of cardiac regeneration, studies have shown a certain degree of benefit when
      treated with MSCs from different origins. The investigators approach is based on a
      decellularized matrix that carries the cells directly over myocardial infarction.

      Among the different types of MSC currently available, the investigators propose the use of
      those derived from the connective tissue surrounding the great vessels (2 arteries and one
      vein) of the umbilical cord called Wharton's gelatin (MSC, WJ) whose immunomodulatory
      properties are described extensively in the literature. These MSC, WJ cells have a PEI
      approved by the Spanish Agency for Medicines and Healthcare Products (AEMPS) (PEI 16-017)
      that guarantees an optimal manufacturing process for a clinical trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: - Experimental group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.
In addition, the matrix-cell construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue.
- Control group: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The randomization will be known exclusively by the cardiac surgery team and the study coordinator, and it will be blind to the patient and to the rest of the investigators team: clinical cardiologist who performs the follow-up, team that performs image tests, core lab that evaluates the imaging tests and the equipment that statistically analyzes the data.
measure: Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.
time frame: at 12 months of follow-up
description: Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment.
measure: Rate of death or rehospitalization due to any cause and / or adverse reactions related to the procedure / product under investigation.
time frame: At 1 week, 3 and 6 months
description: Safety measured with a combined endpoint of serious clinical events (death or rehospitalization due to any cause) and serious adverse reactions related to the investigational treatment
measure: Death rate or rehospitalization due to cardiovascular causes
time frame: At 1 week, 3 , 6and 12 months
description: Death rate or rehospitalization due to cardiovascular causes at week, 3, 6 and 12 months.
measure: Rate of relevant arrhythmias in Holter of 24 hours
time frame: At 1 week, 3 and 12 months
description: Rate of relevant arrhythmias in Holter of 24 hours a week, 3 and 12 months.
measure: Relevant changes in N-terminal B-type natriuretic peptide (NT-proBNP) and High sensitivity troponin I (hsTnI) levels
time frame: At 1 week, 3 and 12 months
description: Relevant changes in NT-proBNP and hsTnI levels at week, 3 and 12 months.
measure: Changes in the necrotic myocardial mass ratio
time frame: At 3 and 12 months
description: Changes in the necrotic myocardial mass ratio due to gadolinium retention at 3 and 12 months.
measure: Changes of regional contractility
time frame: At 3 and 12 months
description: change of regional contractility by nuclear magnetic resonance (NMR) at 3 and 12 months.
measure: Changes in ejection fraction of the left ventricle
time frame: At 3 and 12 months
description: Changes in ejection fraction of the left at 3 and 12 months
measure: changes in left and right ventricular geometric remodeling
time frame: At 3 and 12 months
description: changes in left and right ventricular geometric remodeling at 3 and 12 months
measure: Changes in the score on the quality of life test Short Form 36 Healthy Survey (SF-36).
time frame: At 3 and 12 months
description: Changes in the score on the quality of life test SF-36 will be used at 3 and 12 months. The mínimum value is 0 and the máximum value is 100. Higher scores mean a better outcome.
measure: Changes in the score on the quality of life Kansas City Cardiomyopathy Questionnaire (KCCQ) test in cases of participants with heart failure will be used.
time frame: At 3 and 12 months
description: Changes in the score on the quality of life test KCCQ in cases of participants with heart failure will be used at 3 and 12 months. The test is composed of 23 items. The options for the answers are Likert scales of 1 to 5, 6 or 7 points and the score of each of its dimensions has a theoretical range from 0 to 100, 100 being the best outcome.
measure: monocyte populations and cytokines and chemokines levels
time frame: At screening, day 3 and day 5
description: changes in the monocyte populations and cytokines and chemokines levels between the two groups in order to analyze if the PeriCord could improve these variables
arm group label: Experimental group
arm group type: Experimental
description: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.
In addition, the matrix-cell (PeriCord) construct will be placed on the ischemic area of the non-candidate revascularization area and will be fixed using surgical glue.
PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix .
arm group label: Control group
arm group type: Active Comparator
description: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed.
intervention type: Combination Product
intervention name: PeriCord: Expanded and cryopreserved allogeneic umbilical cord Wharton´s jelly-derived adult mesenchymal stem cells colonized on human pericardial matrix.
description: A matrix-cell construct (PeriCord) will be placed on the ischemic area of the non-candidate revascularization area during a surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization.
arm group label: Experimental group
intervention type: Procedure
intervention name: Surgery by sternotomy
description: The patient will undergo surgery by sternotomy to perform the surgical revascularization of the arteries candidates for revascularization. No additional procedure will be performed only the by-pass.
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Antoni Bayes-Genís, MD, PhD,FESC
role: Principal Investigator
affiliation: Institut del Cor, HUGTiP, IGTP
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Infarction