<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/NCT03753087</url>
  </required_header>
  <id_info>
    <org_study_id>2018-9-25</org_study_id>
    <nct_id>NCT03753087</nct_id>
  </id_info>
  <brief_title>Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus</brief_title>
  <official_title>A Phase 4, Single-center, Randomized, Parallel Group Study to Assess Effects of Empagliflozin on Exercise Capacity and Left Ventricular Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction and Type-2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Medical Research Center for Cardiology, Ministry of Health of Russian Federation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health of the Russian Federation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Medical Research Center for Cardiology, Ministry of Health of Russian Federation</source>
  <oversight_info>
    <is_fda_regulated_drug>No</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>
      Patients enrolled into the study will be randomly allocated either to Empagliflozin group or&#xD;
      control group. In the Empagliflozin group patients will be receiving standard care +&#xD;
      Empagliflozin 10 mg o.d., in the control group patients will be receiving standard care&#xD;
      without sodium glucose contransporter 2 (SGLT2) inhibitors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Actual">January 10, 2022</completion_date>
  <primary_completion_date type="Actual">December 16, 2021</primary_completion_date>
  <phase>Phase 4</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>Change in 6-minute walking distance (6MWD)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular mass index (LVMI)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left atrial volume index (LAVI)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left atrial stiffness</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in left atrial stiffness assessed as a ratio of mitral E/e' ratio to left atrial strain s between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change estimated pulmonary artery systolic pressure (PASP)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in PASP assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average e' velocity</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in average e' velocity assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average E/e' ratio</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in average E/e' ratio assessed by echocardiography both at rest and during diastolic stress between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cyclic guanosine monophosphate (cGMP)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in cGMP plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Endothelin 1 (ET-1)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Growth/differentiation factor 15 (GDF-15)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ST2</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in ST2 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Galectin-3</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in carboxyterminal propeptide of type I collagen (PICP)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in PICP plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Human Pentraxin 3 (PTX3)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in high-sensitivity C-reactive protein (hsCRP)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Interleukin-6 (IL-6)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of New York Heart Association (NYHA) functional classification</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in NYHA class between 24 weeks after baseline and at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score</measure>
    <time_frame>24 weeks</time_frame>
    <description>Difference in MLHFQ score between 24 weeks after baseline and at baseline.&#xD;
The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.&#xD;
Score ranges from 0 (best quality of life) to 105 (worst quality of life).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Heart Failure, Diastolic</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Empagliflozin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Empagliflozin</intervention_name>
    <description>10 mg tablet</description>
    <arm_group_label>Empagliflozin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard care</intervention_name>
    <description>Standard care with no SGLT-2 inhibitors</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females aged 45 to 80 years at screening&#xD;
&#xD;
          2. Diagnosis of type-2 diabetes mellitus with stable glucose-lowering background therapy&#xD;
             for at least 12 weeks&#xD;
&#xD;
          3. HbA1c ≥ 6,5% and ≤ 10% at screening&#xD;
&#xD;
          4. Diagnosis of HFpEF which includes:&#xD;
&#xD;
               -  Symptoms ± signs (as defined in 2016 European Society of Cardiology guidelines&#xD;
                  for the diagnosis and treatment of acute and chronic heart failure)&#xD;
&#xD;
               -  Ejection fraction ≥ 50% (by Simpson)&#xD;
&#xD;
               -  Increased LV filling pressures at rest or during exercise determined by&#xD;
                  echocardiography (LV diastolic dysfunction grade II/III and/or positive diastolic&#xD;
                  stress test) [according to American Society of Echocardiography and European&#xD;
                  Association of Cardiovascular Imaging (ASE/EACVI) Recommendations for the&#xD;
                  Evaluation of Left Ventricular Diastolic Function by Echocardiography, 2016]&#xD;
&#xD;
          5. Signed and dated informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pretreatment with empagliflozin or other SGLT-2 inhibitor within the last 2 months&#xD;
&#xD;
          2. Type-1 diabetes mellitus&#xD;
&#xD;
          3. NYHA classification IV or acute decompensated heart failure at screening&#xD;
&#xD;
          4. Impaired renal function, defined as eGFR &lt;30 ml/min/1.73 m² of body-surface-area&#xD;
             (CKD-EPI)&#xD;
&#xD;
          5. Systolic blood pressure &gt; 180 mmHg or &lt; 90 mmHg&#xD;
&#xD;
          6. Permanent atrial flutter or atrial fibrillation&#xD;
&#xD;
          7. Other conditions that may be responsible for impaired diastolic function such as&#xD;
             hypertrophic/restrictive cardiomyopathy, constrictive pericarditis and etc.&#xD;
&#xD;
          8. Anemia (Hb &lt; 100 g/l)&#xD;
&#xD;
          9. Myocardial infarction, coronary artery bypass graft surgery within the last 3 months&#xD;
&#xD;
         10. Stroke or TIA within the last 3 months&#xD;
&#xD;
         11. Indications of liver disease&#xD;
&#xD;
         12. Acute genital infection or urinary tract infection&#xD;
&#xD;
         13. Pregnancy&#xD;
&#xD;
         14. Additional exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anton Borisov, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Medical Research Center for Cardiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Medical Research Center for Cardiology</name>
      <address>
        <city>Moscow</city>
        <zip>121552</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>January 10, 2022</last_update_submitted>
  <last_update_submitted_qc>January 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Medical Research Center for Cardiology, Ministry of Health of Russian Federation</investigator_affiliation>
    <investigator_full_name>Anton Borisov</investigator_full_name>
    <investigator_title>Principal Investigator, MD</investigator_title>
  </responsible_party>
  <keyword>HF</keyword>
  <keyword>HFpEF</keyword>
  <keyword>DM</keyword>
  <keyword>Empagliflozin</keyword>
  <keyword>Jardiance</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>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Empagliflozin</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/NCT03753087
org study id: 2018-9-25
nct id: NCT03753087
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Patients enrolled into the study will be randomly allocated either to Empagliflozin group or
      control group. In the Empagliflozin group patients will be receiving standard care +
      Empagliflozin 10 mg o.d., in the control group patients will be receiving standard care
      without sodium glucose contransporter 2 (SGLT2) inhibitors.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in 6-minute walking distance (6MWD)
time frame: 24 weeks
description: Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline
measure: Change in left ventricular mass index (LVMI)
time frame: 24 weeks
description: Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
measure: Change in left atrial volume index (LAVI)
time frame: 24 weeks
description: Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
measure: Change in left atrial stiffness
time frame: 24 weeks
description: Difference in left atrial stiffness assessed as a ratio of mitral E/e' ratio to left atrial strain s between 24 weeks after baseline and at baseline
measure: Change estimated pulmonary artery systolic pressure (PASP)
time frame: 24 weeks
description: Difference in PASP assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline
measure: Change in average e' velocity
time frame: 24 weeks
description: Difference in average e' velocity assessed by echocardiography both at rest and during diastolic stress test (DST) between 24 weeks after baseline and at baseline
measure: Change in average E/e' ratio
time frame: 24 weeks
description: Difference in average E/e' ratio assessed by echocardiography both at rest and during diastolic stress between 24 weeks after baseline and at baseline
measure: Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)
time frame: 24 weeks
description: Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline
measure: Change in Cyclic guanosine monophosphate (cGMP)
time frame: 24 weeks
description: Difference in cGMP plasma levels between 24 weeks after baseline and at baseline
measure: Change in Endothelin 1 (ET-1)
time frame: 24 weeks
description: Difference in ET-1 plasma levels between 24 weeks after baseline and at baseline
measure: Change in Growth/differentiation factor 15 (GDF-15)
time frame: 24 weeks
description: Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
measure: Change in ST2
time frame: 24 weeks
description: Difference in ST2 plasma levels between 24 weeks after baseline and at baseline
measure: Change in Galectin-3
time frame: 24 weeks
description: Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
measure: Change in carboxyterminal propeptide of type I collagen (PICP)
time frame: 24 weeks
description: Difference in PICP plasma levels between 24 weeks after baseline and at baseline
measure: Change in Human Pentraxin 3 (PTX3)
time frame: 24 weeks
description: Difference in PTX3 plasma levels between 24 weeks after baseline and at baseline
measure: Change in high-sensitivity C-reactive protein (hsCRP)
time frame: 24 weeks
description: Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
measure: Change in Interleukin-6 (IL-6)
time frame: 24 weeks
description: Difference in IL-6 plasma levels between 24 weeks after baseline and at baseline
measure: Change of New York Heart Association (NYHA) functional classification
time frame: 24 weeks
description: Difference in NYHA class between 24 weeks after baseline and at baseline
measure: Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score
time frame: 24 weeks
description: Difference in MLHFQ score between 24 weeks after baseline and at baseline.
The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.
Score ranges from 0 (best quality of life) to 105 (worst quality of life).
arm group label: Empagliflozin
arm group type: Experimental
description: Patients will receive standard care for Heart Failure and Diabetes Mellitus + Empagliflozin 10mg once daily
arm group label: Control
arm group type: Active Comparator
description: Patients will receive standard care for Heart Failure and Diabetes Mellitus with no SGLT-2 inhibitors
intervention type: Drug
intervention name: Empagliflozin
description: 10 mg tablet
arm group label: Empagliflozin
intervention type: Other
intervention name: Standard care
description: Standard care with no SGLT-2 inhibitors
arm group label: Control
criteria: 
gender: All
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: No
last name: Anton Borisov, MD
role: Principal Investigator
affiliation: National Medical Research Center for Cardiology
facility: 
country: Russian Federation
responsible party type: Principal Investigator
investigator affiliation: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
investigator full name: Anton Borisov
investigator title: Principal Investigator, MD
mesh term: Heart Failure
mesh term: Heart Failure, Diastolic
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Empagliflozin