<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/NCT04498780</url>
  </required_header>
  <id_info>
    <org_study_id>DL-L-20005_V1.4</org_study_id>
    <nct_id>NCT04498780</nct_id>
  </id_info>
  <brief_title>Hemodynamic Effects of ARNI on Noninvasive Pressure-volume Analysis in Patients With Chronic Heart Failure</brief_title>
  <acronym>ARNI-PVA</acronym>
  <official_title>Hemodynamic Effects of Angiotensin Receptor Neprilysin Inhibition on Noninvasive Pressure-volume Analysis in Patients With Heart Failure With Reduced Ejection Fraction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leipzig</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Leipzig</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sacubitril-Valsartan reduced heart failure hospitalizations and cardiovascular mortality&#xD;
      compared to enelapril in chronic heart failure. Furthermore, quality of life is improved. The&#xD;
      decrease of NT-proBNP levels during Sacubitril-Valsartan treatment is associated with reverse&#xD;
      left ventricular remodeling and improved left ventricular systolic function. However, the&#xD;
      underlying mechanisms that contribute to these symptomatic and prognostic benefits are&#xD;
      largely unknown. The aim of this study is to evaluate left ventricular hemodynamics in&#xD;
      patients treated with Sacubitril-Valsartan using non-invasive pressure-volume analysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 21, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>12 Months</target_duration>
  <primary_outcome>
    <measure>Left ventricular contractility, afterload and ventricular-arterial coupling</measure>
    <time_frame>6 months</time_frame>
    <description>Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systolic and diastolic LV function, symptom status and biomarkers</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Echocardiography: Left ventricular (LV) remodeling und function (LVEDV, LVESV, LVEF, GLS), diastolic LV function (LAESV, E/e', LVEDP)&#xD;
Symptoms: NYHA functional class, 6 minute walk test&#xD;
Biomarker: NT-proBNP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular contractility, afterload and ventricular-arterial coupling</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Load-independent parameters of systolic and diastolic LV function, myocardial work indices</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Peak power index (PPI)&#xD;
Preload-recruitable stroke work (PRSW)&#xD;
End-systolic meridional wall stress (EsMWS)&#xD;
Total peripheral resistance (TPR)&#xD;
LV end-systolic pressure (LVEDP)&#xD;
LV end-diastolic pressure-volume relationship (LVEDPVR)&#xD;
Pressure-strain loops</description>
  </other_outcome>
  <enrollment type="Actual">117</enrollment>
  <condition>Heart Failure With Reduced Ejection Fraction</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sacubitril-Valsartan</intervention_name>
    <description>Observational study during the clinically indicated treatment</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with symptomatic heart failure (NYHA functional class II to IV) and reduced&#xD;
        ejection fraction (LVEF≤40%) with clinical indication for therapy with Sacubitril-Valsartan&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptomatic heart failure (NYHA functional class II to IV)&#xD;
&#xD;
          -  Reduced LV ejection fraction (≤ 40%)&#xD;
&#xD;
          -  Clinical indication for therapy with Sacubitril-Valsartan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  catecholamine therapy at inclusion&#xD;
&#xD;
          -  existing therapy with Sacubitril-Valsartan&#xD;
&#xD;
          -  planned cardiac resynchronization therapy (CRT) within 6 months; inclusion at least 3&#xD;
             months after CRT&#xD;
&#xD;
          -  planned mitral or aortic valve procedure within 6 months; inclusion at least 3 months&#xD;
             after valve procedure&#xD;
&#xD;
          -  participation in another randomized heart failure trial&#xD;
&#xD;
          -  severe aortic or mitral valve lesion&#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>Daniel Lavall, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Leipzig</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Leipzig</name>
      <address>
        <city>Leipzig</city>
        <state>Saxony</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kardiopraxis Schirmer</name>
      <address>
        <city>Kaiserslautern</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Leipzig</investigator_affiliation>
    <investigator_full_name>Daniel Lavall</investigator_full_name>
    <investigator_title>Dr. med. Daniel Lavall</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_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/NCT04498780
org study id: DL-L-20005_V1.4
nct id: NCT04498780
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Sacubitril-Valsartan reduced heart failure hospitalizations and cardiovascular mortality
      compared to enelapril in chronic heart failure. Furthermore, quality of life is improved. The
      decrease of NT-proBNP levels during Sacubitril-Valsartan treatment is associated with reverse
      left ventricular remodeling and improved left ventricular systolic function. However, the
      underlying mechanisms that contribute to these symptomatic and prognostic benefits are
      largely unknown. The aim of this study is to evaluate left ventricular hemodynamics in
      patients treated with Sacubitril-Valsartan using non-invasive pressure-volume analysis.
observational model: Cohort
time perspective: Prospective
measure: Left ventricular contractility, afterload and ventricular-arterial coupling
time frame: 6 months
description: Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)
measure: Systolic and diastolic LV function, symptom status and biomarkers
time frame: 3, 6 and 12 months
description: Echocardiography: Left ventricular (LV) remodeling und function (LVEDV, LVESV, LVEF, GLS), diastolic LV function (LAESV, E/e', LVEDP)
Symptoms: NYHA functional class, 6 minute walk test
Biomarker: NT-proBNP
measure: Left ventricular contractility, afterload and ventricular-arterial coupling
time frame: 3 and 12 months
description: Change of end-systolic elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees)
measure: Load-independent parameters of systolic and diastolic LV function, myocardial work indices
time frame: 3, 6 and 12 months
description: Peak power index (PPI)
Preload-recruitable stroke work (PRSW)
End-systolic meridional wall stress (EsMWS)
Total peripheral resistance (TPR)
LV end-systolic pressure (LVEDP)
LV end-diastolic pressure-volume relationship (LVEDPVR)
Pressure-strain loops
intervention type: Drug
intervention name: Sacubitril-Valsartan
description: Observational study during the clinically indicated treatment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Lavall, MD
role: Principal Investigator
affiliation: University of Leipzig
facility: 
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Leipzig
investigator full name: Daniel Lavall
investigator title: Dr. med. Daniel Lavall
mesh term: Heart Failure
mesh term: Valsartan
mesh term: Sacubitril and valsartan sodium hydrate drug combination