<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/NCT04490681</url>
  </required_header>
  <id_info>
    <org_study_id>4-2020-0484</org_study_id>
    <nct_id>NCT04490681</nct_id>
  </id_info>
  <brief_title>Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)</brief_title>
  <official_title>Validation of ERTugliflozin for Inhibiting Cardiac Fibrosis Using Cardiac MRI and Laboratory Parameters in Korean Heart Failure Patients With Nonischemic Cardiomyopathy(VERTICAL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</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>
      Based on recent studies demonstrating SGLT2 inhibitors' favorable effects on cardiovascular&#xD;
      outcomes especially for heart failure, the investigators hypothesize that sodium-glucose&#xD;
      co-transporter-2 (SGLT2) inhibitor, ertugliflozin, is effective on reducing cardiac fibrosis&#xD;
      in patients with nonischemic cardiomyopathy so the investigators try to examine this&#xD;
      hypothesis in a single-center, double-blind, randomized controlled study using cardiac&#xD;
      magnetic resonance (CMR).&#xD;
&#xD;
      This study is a prospective, single-center, randomized, double-blind, two arm parallel group,&#xD;
      placebo-controlled clinical trial involving patients with nonischemic cardiomyopathy.&#xD;
      Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 to&#xD;
      ertugliflozin or placebo therapy, and cardiovascular functional assessment and clinical event&#xD;
      follow-up will be undertaken.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects : Patients with non-ischemic cardiomyopathy who need medical treatment Procedures :&#xD;
      This is a prospective, randomized trial to compare cardiopulmonary motor tests, cardiac MRI&#xD;
      including myocardial fibrosis parameters (ECV, etc.), and incidence of various heart&#xD;
      failure-related cardiovascular events during the follow-up period between patients with&#xD;
      ertugliflozin drug therapy and placebo drug. Patients meeting inclusion criteria without any&#xD;
      exclusion criteria will be randomized 1:1 to ertugliflozin (5mg) or placebo therapy.&#xD;
      Randomization will be stratified according to presence of diabetes mellitus, and the upper&#xD;
      limit of randomized non-DM patients will be set as 36 patients (70%). The estimated&#xD;
      enrollment period is 18 months (n=52) and all patients will be followed for 12 months after&#xD;
      randomization. Random assignment is performed at random assignment visit (V1) through eCASE&#xD;
      web system and following study procedures will be conducted according to the randomization.&#xD;
      CMR, Cardiopulmonary exercise test, serum biomarkers, and clinical endpoints will be measured&#xD;
      at 3,6,12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Due to the nature of randomized study, it will be masked to all participants, care providers, investigators, and outcomes assessors.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration</measure>
    <time_frame>Baseline</time_frame>
    <description>The ECV value change in MRI from baseline to End of trial (48 weeks)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration</measure>
    <time_frame>48 Weeks after drug administration</time_frame>
    <description>The ECV value change in MRI from baseline to End of trial (48 weeks)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : ECV (%)</measure>
    <time_frame>baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : ECV (%)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : ECV (%)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : Native T1 (ms)</measure>
    <time_frame>baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : Native T1 (ms)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : Native T1 (ms)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : left &amp; right ventricular (LV &amp; RV) mass index (g/m2)</measure>
    <time_frame>Baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : left &amp; right ventricular (LV &amp; RV) mass index (g/m2)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : left &amp; right ventricular (LV &amp; RV) mass index (g/m2)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV ejection fraction (%)</measure>
    <time_frame>Baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV ejection fraction (%)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV ejection fraction (%)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume (ml)</measure>
    <time_frame>Baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume (ml)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume (ml)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : cine-base cardiac strain (%)</measure>
    <time_frame>Baseline</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : cine-base cardiac strain (%)</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMR parameters : cine-base cardiac strain (%)</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left &amp; right ventricular (LV &amp; RV) mass index), ventricular functional markers (LV &amp; RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV &amp; RV end-systolic volume, LV &amp; RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7</measure>
    <time_frame>baseline</time_frame>
    <description>The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7</measure>
    <time_frame>12 weeks after drug administration</time_frame>
    <description>The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7</measure>
    <time_frame>24 weeks after drug administration</time_frame>
    <description>The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7</measure>
    <time_frame>48 weeks after drug administration</time_frame>
    <description>The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">52</enrollment>
  <condition>Heart Failure With Nonischemic Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Ertugliflozin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ertugliflozin 5mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ertugliflozin</intervention_name>
    <description>Fixed dose Ertugliflozin (5mg)</description>
    <arm_group_label>Ertugliflozin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo group</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must agree to the study protocol and provide written informed consent&#xD;
&#xD;
          -  Outpatients ≥ 19 years, &lt;75 years of age, male or female&#xD;
&#xD;
          -  Non-diabetic or type 2 DM patients with HbA1c 7.0-10.5%&#xD;
&#xD;
          -  Patients with nonischemic cardiomyopathy (LVEF ≤40%)&#xD;
&#xD;
          -  Exclusion of ischemic origin cardiomyopathy using coronary angiography or CT&#xD;
             angiography or SPECT scan (e.g. significant stenosis of proximal LAD or left main &amp;&#xD;
             myocardial infarction)&#xD;
&#xD;
          -  Dyspnea of NYHA functional class II or III&#xD;
&#xD;
          -  NT-proBNP ≥ 400 pg/ml (≥ 900 pg/ml if atrial fibrillation or atrial flutter)&#xD;
&#xD;
          -  Titration of HF medications should be completed and patients must take a stable,&#xD;
             optimized dose of a β-blocker and an ACE inhibitor (or ARB or ARNI if indicated) for&#xD;
             at least 4 weeks prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity or allergy to the study drug, drugs of similar chemical&#xD;
             classes, or SGLT-2 as well as known or suspected contraindications to the study drug&#xD;
&#xD;
          -  Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor&#xD;
&#xD;
          -  Known history of angioedema&#xD;
&#xD;
          -  Current acute decompensated heart failure or dyspnea of NYHA functional class IV&#xD;
&#xD;
          -  Medical history of hospitalization within 6 weeks&#xD;
&#xD;
          -  Acute coronary syndrome, stroke, major CV surgery, PCI within 3 months&#xD;
&#xD;
          -  Substantial myocardial ischemia requiring coronary revascularization therapy or a plan&#xD;
             of coronary revascularization within 6 months&#xD;
&#xD;
          -  A plan of heart transplantation or implantation of cardiac resynchronization therapy&#xD;
&#xD;
          -  Symptomatic hypotension and/or a SBP &lt; 95 mmHg at screening&#xD;
&#xD;
          -  Estimated GFR &lt; 30 mL/min/1.73m2&#xD;
&#xD;
          -  History of ketoacidosis&#xD;
&#xD;
          -  Symptomatic peripheral artery disease and history of lower limb amputation&#xD;
&#xD;
          -  Evidence of hepatic disease as determined by any one of the following: AST or ALT&#xD;
             values exceeding 3 x upper limit of normal (ULN) at screening visit (Visit 0), history&#xD;
             of hepatic encephalopathy, history of esophageal varices, or history of portacaval&#xD;
             shunt.&#xD;
&#xD;
          -  History of severe pulmonary disease&#xD;
&#xD;
          -  Significant mitral &amp; aortic valve disease (e.g. moderate to severe, severe degree)&#xD;
&#xD;
          -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using a barrier method plus a hormonal method&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
&#xD;
          -  Any clinically significant abnormality identified at the screening visit, physical&#xD;
             examination, laboratory tests, or electrocardiogram which, in the judgment of the&#xD;
             investigator, would preclude safe completion of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Seok-Min Kang</last_name>
    <phone>82-2-2228-8450</phone>
    <email>smkang@yuhs.ac</email>
  </overall_contact>
  <location>
    <facility>
      <name>Severance Hospiatal</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <contact>
      <last_name>Seok-Min Kang</last_name>
      <phone>82-2-2228-8450</phone>
      <email>smkang@yuhs.ac</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>August 5, 2020</last_update_submitted>
  <last_update_submitted_qc>August 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ertugliflozin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04490681
org study id: 4-2020-0484
nct id: NCT04490681
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Based on recent studies demonstrating SGLT2 inhibitors' favorable effects on cardiovascular
      outcomes especially for heart failure, the investigators hypothesize that sodium-glucose
      co-transporter-2 (SGLT2) inhibitor, ertugliflozin, is effective on reducing cardiac fibrosis
      in patients with nonischemic cardiomyopathy so the investigators try to examine this
      hypothesis in a single-center, double-blind, randomized controlled study using cardiac
      magnetic resonance (CMR).

      This study is a prospective, single-center, randomized, double-blind, two arm parallel group,
      placebo-controlled clinical trial involving patients with nonischemic cardiomyopathy.
      Patients meeting inclusion criteria without any exclusion criteria will be randomized 1:1 to
      ertugliflozin or placebo therapy, and cardiovascular functional assessment and clinical event
      follow-up will be undertaken.
Subjects : Patients with non-ischemic cardiomyopathy who need medical treatment Procedures :
      This is a prospective, randomized trial to compare cardiopulmonary motor tests, cardiac MRI
      including myocardial fibrosis parameters (ECV, etc.), and incidence of various heart
      failure-related cardiovascular events during the follow-up period between patients with
      ertugliflozin drug therapy and placebo drug. Patients meeting inclusion criteria without any
      exclusion criteria will be randomized 1:1 to ertugliflozin (5mg) or placebo therapy.
      Randomization will be stratified according to presence of diabetes mellitus, and the upper
      limit of randomized non-DM patients will be set as 36 patients (70%). The estimated
      enrollment period is 18 months (n=52) and all patients will be followed for 12 months after
      randomization. Random assignment is performed at random assignment visit (V1) through eCASE
      web system and following study procedures will be conducted according to the randomization.
      CMR, Cardiopulmonary exercise test, serum biomarkers, and clinical endpoints will be measured
      at 3,6,12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Due to the nature of randomized study, it will be masked to all participants, care providers, investigators, and outcomes assessors.
measure: The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration
time frame: Baseline
description: The ECV value change in MRI from baseline to End of trial (48 weeks)
measure: The ECV value change in CMR after Drug (Ertugliflozin or Placebo) administration
time frame: 48 Weeks after drug administration
description: The ECV value change in MRI from baseline to End of trial (48 weeks)
measure: CMR parameters : ECV (%)
time frame: baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : ECV (%)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : ECV (%)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : Native T1 (ms)
time frame: baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : Native T1 (ms)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : Native T1 (ms)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
time frame: Baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : left & right ventricular (LV & RV) mass index (g/m2)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV ejection fraction (%)
time frame: Baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV ejection fraction (%)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV ejection fraction (%)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
time frame: Baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : LV & RV end-systolic volume, LV & RV end-diastolic volume (ml)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : cine-base cardiac strain (%)
time frame: Baseline
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : cine-base cardiac strain (%)
time frame: 12 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: CMR parameters : cine-base cardiac strain (%)
time frame: 48 weeks after drug administration
description: CMR parameters : the changes of myocardial fibrosis markers (ECV, Native T1), ventricular muscle mass marker (left & right ventricular (LV & RV) mass index), ventricular functional markers (LV & RV ejection fraction, cine-base cardiac strain), and ventricular remodeling markers (LV & RV end-systolic volume, LV & RV end-diastolic volume). These parameters represent myocardial fibrotic change, ventricular remodelling, systolic function.
measure: Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
time frame: baseline
description: The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
measure: Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
time frame: 12 weeks after drug administration
description: The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
measure: Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
time frame: 24 weeks after drug administration
description: The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
measure: Biomarkers : NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7
time frame: 48 weeks after drug administration
description: The change in degree of NT-proBNP, hsTn, soluble ST2, galectin-3, IGFBP7 after drug administration.
arm group label: Ertugliflozin
arm group type: Experimental
description: Ertugliflozin 5mg
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Ertugliflozin
description: Fixed dose Ertugliflozin (5mg)
arm group label: Ertugliflozin
intervention type: Drug
intervention name: Placebo
description: Placebo group
arm group label: placebo
criteria: 
gender: All
minimum age: 19 Years
maximum age: 74 Years
healthy volunteers: No
last name: Seok-Min Kang
phone: 82-2-2228-8450
email: smkang@yuhs.ac
facility: 
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Cardiomyopathies
mesh term: Ertugliflozin
sharing ipd: No