<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/NCT03240237</url>
  </required_header>
  <id_info>
    <org_study_id>ID_CP_OPT2016-012_0</org_study_id>
    <nct_id>NCT03240237</nct_id>
  </id_info>
  <brief_title>CCM in Heart Failure With Preserved Ejection Fraction</brief_title>
  <acronym>CCM-HFpEF</acronym>
  <official_title>Cardiac Contractility Modulation Therapy in Subjects With Heart Failure With Preserved Ejection Fraction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Impulse Dynamics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Impulse Dynamics</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>
      This pilot study will evaluate the efficacy and safety of CCM therapy in heart failure&#xD;
      patients with baseline EF≥50% (HFpEF) who have New York Heart Association (NYHA) Class II or&#xD;
      III symptoms despite appropriate medication.&#xD;
&#xD;
      The terminology of the HF classification HFpEF is based on the 2016 European Society of&#xD;
      Cardiology (ESC) Heart Failure Guidelines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot clinical study of CCM in addition to optimal medical therapy (OMT) over a 24&#xD;
      week period.The primary endpoint shall be mean change from baseline to 24 weeks in Kansas&#xD;
      City Cardiomyopathy Questionnaire (KCCQ) overall score (reflecting integrated information on&#xD;
      physical limitations, symptoms, self-efficacy, social interference and quality of life).&#xD;
&#xD;
      This pilot study will collect efficacy and safety data in heart failure patients having NYHA&#xD;
      class II and III symptoms despite appropriate medication with baseline ejection fraction&#xD;
      equal or greater than 50% (HFpEF populations).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 1, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This pilot study is designed and powered for evaluating the efficacy and safety of CCM therapy in heart failure patients with baseline EF≥50% (HFpEF) who have NYHA Class II or III symptoms despite appropriate medication, for potential expansion of the CE Mark indication for use in the HFpEF population.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>KCCQ change</measure>
    <time_frame>24 weeks</time_frame>
    <description>Mean change from baseline to 24 weeks in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Echocardiography</measure>
    <time_frame>24 weeks</time_frame>
    <description>LAVi and diastolic function: septal E' velocity, septal E/E' ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NT-proBNP</measure>
    <time_frame>24 weeks</time_frame>
    <description>Mean Change in 24 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NYHA class</measure>
    <time_frame>24 weeks</time_frame>
    <description>Mean Change in 24 weeks</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Heart Failure, Diastolic</condition>
  <arm_group>
    <arm_group_label>CCM therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optimizer SMART</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Optimizer SMART</intervention_name>
    <description>Cardiac Contractility Modulation</description>
    <arm_group_label>CCM therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Inclusion criteria&#xD;
&#xD;
               1. Baseline ejection fraction ≥ 50% (as assessed by echocardiogram within 30 days of&#xD;
                  enrollment and confirmed by the echo core laboratory).&#xD;
&#xD;
               2. NYHA class II or III symptoms despite receiving stable optimal medical therapy&#xD;
                  (OMT) for at least 30 days based on patient's medical records (chronic stable,&#xD;
                  not transient or crescendo heart failure or angina pectoris)&#xD;
&#xD;
               3. Stable optimal medical therapy for Heart failure for 3 months.&#xD;
&#xD;
               4. NT-proBNP &gt; 220 pg/ml for subjects in sinus rhythm or &gt; 600 pg/ml for subjects in&#xD;
                  atrial fibrillation&#xD;
&#xD;
               5. Has the following (as assessed by the core lab):&#xD;
&#xD;
                    -  LAVi ≥ 34 ml/m² or LVH &gt;12mm AND either&#xD;
&#xD;
                    -  E/e' ≥ 13 OR&#xD;
&#xD;
                    -  septal e' &lt; 7 cm/s or lateral e' &lt;10 cm/s&#xD;
&#xD;
               6. Patient giving informed consent, willing to be available for scheduled study&#xD;
                  follow-up visits, and able to complete all testing of the study protocol&#xD;
&#xD;
          2. Exclusion criteria&#xD;
&#xD;
               1. Age below 40 or greater than 80&#xD;
&#xD;
               2. Patients with expected lifespan of less than 12 months from time of enrollment&#xD;
&#xD;
               3. Subjects referred to an institution based on a judicial or administrative order&#xD;
&#xD;
               4. Dilated left ventricle, as evidenced by LVEDVI &gt;= 97 mL/m2 (as assessed by the&#xD;
                  echo core lab)&#xD;
&#xD;
               5. Primary cardiac valvular disease (anything more than grade 2)&#xD;
&#xD;
               6. Congenital or untreated ischemic heart disease&#xD;
&#xD;
               7. Infiltrative / inflammatory / genetic cardiomyopathy as documented in the medical&#xD;
                  record (e.g. amyloid, hemochromatosis, myocarditis, hypertrophic cardiomyopathy,&#xD;
                  M. Fabry, cardiac tumor), or persistent large pericardial effusion&#xD;
&#xD;
               8. Unstable or frequent (&gt;1 episode/week) angina pectoris&#xD;
&#xD;
               9. Hospitalization for HF requiring the use of inotropic support or IABP within 30&#xD;
                  days of enrollment&#xD;
&#xD;
              10. Systolic Blood Pressure &gt; 160 mmHg&#xD;
&#xD;
              11. Uncorrected severe anemia (e.g. hemoglobin &lt;9g/dL)&#xD;
&#xD;
              12. PR interval greater than 375 ms&#xD;
&#xD;
              13. Exercise tolerance limited due to noncardiac disorders (e.g. deconditioning,&#xD;
                  severe lung disease, frailty)&#xD;
&#xD;
              14. Scheduled for a cardiac surgery or a PCI procedure, or had a cardiac surgery&#xD;
                  procedure within 90 days or a PCI procedure within 30 days prior to enrollment&#xD;
&#xD;
              15. Myocardial infarction within 90 days of enrollment&#xD;
&#xD;
              16. Cardioversion within 30 days of enrollment&#xD;
&#xD;
              17. History of significant ectopy either on 12-lead ECG or Holter monitoring (more&#xD;
                  than 10% PVCs).&#xD;
&#xD;
              18. Heart rate &gt; 110 bpm on ECG for patients with atrial fibrillation&#xD;
&#xD;
              19. Mechanical tricuspid valve&#xD;
&#xD;
              20. Prior heart transplant or ventricular assist device&#xD;
&#xD;
              21. Pregnant or planning to become pregnant during the study&#xD;
&#xD;
              22. Breastfeeding subjects&#xD;
&#xD;
              23. Subject participating in another medical therapy or device related study,&#xD;
                  unrelated to CCM™, at the same time or within 30 days prior to enrollment into&#xD;
                  this study&#xD;
&#xD;
              24. Subjects on dialysis, or with documented GFR&lt;30 or with other major medical&#xD;
                  disorder (e.g. severe anemia, liver failure)&#xD;
&#xD;
              25. Subjects with any active non-cardiac implants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carsten Tschoepe, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Charite Berlin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Friendly Society Private Hospital</name>
      <address>
        <city>Bundaberg</city>
        <state>Queensland</state>
        <zip>4670</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John of God Bunbury</name>
      <address>
        <city>Bunbury</city>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John of God Murdoch Hospital</name>
      <address>
        <city>Perth</city>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Na Homolce</name>
      <address>
        <city>Praha 5</city>
        <zip>15030</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kerckhoff-Klinik GmbH</name>
      <address>
        <city>Bad Nauheim</city>
        <state>Hesse</state>
        <zip>61231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INRCA IRCCS Ancona</name>
      <address>
        <city>Ancona</city>
        <state>Rome</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auxologico Institute</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Rome</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego zakład leczniczy Centralnego Szpitala Klinicznego</name>
      <address>
        <city>Warsaw</city>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>4 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ we Wroclawiu</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-981</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny we Wrocław</name>
      <address>
        <city>Wrocław</city>
        <zip>50-556</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Lisbon Hospital Center, E.P.E., hereinafter referred to as CHLO, E.P.E</name>
      <address>
        <city>Lisbon</city>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santiago de Compostella -- Servicio de Cardiología y UCC/ Cardiology and Coronary Care Department Hospital Clínico Universitario. XXI de Santiago de Compostela SERGAS</name>
      <address>
        <city>Santiago De Compostela</city>
        <state>C/ A Choupana S.n</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>3010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre Unidad de Insuficiencia Cardiaca y Trasplante Servicio de Cardiología, Planta 6. Bloque D.Ciber 8</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Alvaro Cunquero</name>
      <address>
        <city>Vigo</city>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>Sweden</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
    <country>Lithuania</country>
  </removed_countries>
  <reference>
    <citation>Tschope C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016 Jan 15;203:1061-6. doi: 10.1016/j.ijcard.2015.10.208. Epub 2015 Oct 27. No abstract available.</citation>
    <PMID>26638055</PMID>
  </reference>
  <results_reference>
    <citation>Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A, Tschope C. Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF). Eur J Heart Fail. 2022 Dec;24(12):2275-2284. doi: 10.1002/ejhf.2619. Epub 2022 Aug 11.</citation>
    <PMID>35855646</PMID>
  </results_reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HFpEF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Heart Failure, Diastolic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03240237
org study id: ID_CP_OPT2016-012_0
nct id: NCT03240237
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This pilot study will evaluate the efficacy and safety of CCM therapy in heart failure
      patients with baseline EF≥50% (HFpEF) who have New York Heart Association (NYHA) Class II or
      III symptoms despite appropriate medication.

      The terminology of the HF classification HFpEF is based on the 2016 European Society of
      Cardiology (ESC) Heart Failure Guidelines.
This is a pilot clinical study of CCM in addition to optimal medical therapy (OMT) over a 24
      week period.The primary endpoint shall be mean change from baseline to 24 weeks in Kansas
      City Cardiomyopathy Questionnaire (KCCQ) overall score (reflecting integrated information on
      physical limitations, symptoms, self-efficacy, social interference and quality of life).

      This pilot study will collect efficacy and safety data in heart failure patients having NYHA
      class II and III symptoms despite appropriate medication with baseline ejection fraction
      equal or greater than 50% (HFpEF populations).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This pilot study is designed and powered for evaluating the efficacy and safety of CCM therapy in heart failure patients with baseline EF≥50% (HFpEF) who have NYHA Class II or III symptoms despite appropriate medication, for potential expansion of the CE Mark indication for use in the HFpEF population.
primary purpose: Other
masking: None (Open Label)
measure: KCCQ change
time frame: 24 weeks
description: Mean change from baseline to 24 weeks in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score
measure: Echocardiography
time frame: 24 weeks
description: LAVi and diastolic function: septal E' velocity, septal E/E' ratio
measure: NT-proBNP
time frame: 24 weeks
description: Mean Change in 24 weeks
measure: NYHA class
time frame: 24 weeks
description: Mean Change in 24 weeks
arm group label: CCM therapy
arm group type: Experimental
description: Optimizer SMART
intervention type: Device
intervention name: Optimizer SMART
description: Cardiac Contractility Modulation
arm group label: CCM therapy
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Carsten Tschoepe, Prof.
role: Principal Investigator
affiliation: University Hospital Charite Berlin
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Czechia
country: Germany
country: Italy
country: Poland
country: Portugal
country: Spain
country: Sweden
country: France
country: Lithuania
citation: Tschope C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016 Jan 15;203:1061-6. doi: 10.1016/j.ijcard.2015.10.208. Epub 2015 Oct 27. No abstract available.
PMID: 26638055
citation: Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A, Tschope C. Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF). Eur J Heart Fail. 2022 Dec;24(12):2275-2284. doi: 10.1002/ejhf.2619. Epub 2022 Aug 11.
PMID: 35855646
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Heart Failure, Diastolic
sharing ipd: Undecided