xml: <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/NCT05973591</url>
    </required_header>
    <id_info>
      <org_study_id>4-2022-1665</org_study_id>
      <nct_id>NCT05973591</nct_id>
    </id_info>
    <brief_title>The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era</brief_title>
    <official_title>The Impact of Ivabradine on Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (NIDCM) on Current Medical Therapy Era</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>
        In non-ischemic dilated cardiomyopathy (NIDCM), left ventricular reverse remodeling (LVRR)&#xD;
        can be achieved through guideline-directed medical therapy (GDMT). LVRR is defined as an&#xD;
        increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure&#xD;
        patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% at&#xD;
        follow-up, which is classified as heart failure with improved EF (HFimpEF) according to&#xD;
        current guidelines. Several studies have examined the prevalence and predictors of LVRR in&#xD;
        NIDCM. However, there is a lack of research on LVRR in the context of contemporary&#xD;
        pharmacotherapy. Studies have demonstrated the beneficial effects of ivabradine in heart&#xD;
        failure with reduced ejection fraction (HFrEF), improving patients' prognosis. A sub-study of&#xD;
        the SHIFT trial indicated that ivabradine may also contribute to cardiac remodeling reversal&#xD;
        in patients with HFrEF. However, there is limited evidence exploring the relationship between&#xD;
        ivabradine and LVRR, particularly in the context of NIDCM.&#xD;
  &#xD;
        Consequently, this study is a retrospective, multi-center cohort study aiming to evaluate the&#xD;
        impact of ivabradine on LVRR in patients with NIDCM in the current era of medical therapy.&#xD;
        Furthermore, by conducting this study, we aim to gain insights into the potential role of&#xD;
        ivabradine in promoting LVRR in NIDCM patients receiving contemporary drug therapy.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">July 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Prevalence of of LVRR in patients with NIDCM</measure>
      <time_frame>at 12 months after the initiation of GDMT</time_frame>
      <description>LVRR is characterized by an increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% during follow-up, which is classified as heart failure with improved EF (HFimpEF). Furthermore, the initiation of guideline-directed medical therapy (GDMT) is defined as the timeframe for commencing treatment with an angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor antagonist (ARB), or beta-blocker after the diagnosis of heart failure with reduced ejection fraction (HFrEF).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Prevalence of LVRR in NIDCM at 8 months after initiation of GDMT</measure>
      <time_frame>at 8 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Extent of LVRR (measured by LVEDD/LVESD, LAVI, E/e' in echocardiography) in NIDCM at 8 and 12 months after GDMT initiation</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical course of LVRR in NIDCM</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of targeted HR (HF &lt;60 or 70/min) on LVRR in NIDCM at 8 and 12 months after GDMT initiation</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of degree of change in HR before and after GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Impact of GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Prevalence of symptomatic bradycardia, syncope, or any other adverse events with Ivabradine</measure>
      <time_frame>at 8 and 12 months after GDMT initiation</time_frame>
    </secondary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">500</enrollment>
    <condition>Dilated Cardiomyopathy</condition>
    <condition>Ventricular Remodeling</condition>
    <condition>Heart Failure, Reduced Ejection Fraction</condition>
    <arm_group>
      <arm_group_label>achieved HR ≥ 70 bpm without ivabradine</arm_group_label>
      <description>**Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**</description>
    </arm_group>
    <arm_group>
      <arm_group_label>achieved HR &lt; 70 bpm without ivabradine</arm_group_label>
      <description>**Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**</description>
    </arm_group>
    <arm_group>
      <arm_group_label>achieved HR ≥ 70 bpm with ivabradine</arm_group_label>
      <description>**Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**</description>
    </arm_group>
    <arm_group>
      <arm_group_label>achieved HR &lt; 70 bpm with ivabradine</arm_group_label>
      <description>**Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Patients diagnosed with NIDCM with sinus rhythm&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Diagnosed with non-ischemic dilated cardiomyopathy (NIDCM) by performing coronary&#xD;
               artery imaging (coronary angiography, CT angiography, or SPECT scan) at the time of&#xD;
               diagnosis of HFrEF&#xD;
  &#xD;
            2. Sinus rhythm&#xD;
  &#xD;
            3. Baseline LVEF of 40% or less (LVEF≤40%)&#xD;
  &#xD;
            4. Patients containing baseline heart rate (HR)&#xD;
  &#xD;
                 -  In the Ivabradine group, baseline HR must be &gt;75 bpm at the time of ivabradine&#xD;
                    dosing.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with confirmed ischemic cardiomyopathy (when stenosis of 75% or more of major&#xD;
               coronary arteries is confirmed on coronary artery imaging or ischemic cardiomyopathy&#xD;
               findings such as transmural LGE on cardiac MRI)&#xD;
  &#xD;
            2. Heart failure with other etiologies (e.g., valvular heart disease, endocrine disease).&#xD;
  &#xD;
            3. Previous recovery history of left ventricular systolic function (LVEF)&#xD;
  &#xD;
            4. Cardiac resynchronization therapy (CRT) implantation&#xD;
  &#xD;
            5. Persistent/permanent atrial fibrillation&#xD;
  &#xD;
          7) Contraindication to the administration of ivabradine according to the Summary of Product&#xD;
          Characteristics (SmPC)&#xD;
  &#xD;
            -  Hypersensitivity reactions&#xD;
  &#xD;
            -  Symptomatic bradycardia or resting heart rate &lt; 75 bpm prior to treatment&#xD;
  &#xD;
            -  Cardiogenic shock, acute myocardial infarction, severe hypotension (&lt; 90/50 mmHg),&#xD;
               severe hepatic failure, sinus syndrome, atrial block, unstable or acute heart failure,&#xD;
               pacemaker dependence (with pacing dominance), unstable angina, third degree&#xD;
               atrioventricular block&#xD;
  &#xD;
            -  Cytochrome P450 3A4 inhibitors: Azole class antifungals (ketoconazole,itraconazole),&#xD;
               Macrolide class antibiotics (clarithromycin, erythromycin per os, josamycin,&#xD;
               telithromycin), HIV protease inhibitors (nelfinavir, ritonavir), nefazodone or any&#xD;
               concomitant use with verapamil or diltiazem (moderate CYP3A4 inhibitors with heart&#xD;
               rate reducing properties).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Seok-Min Kang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Severance hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 16, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</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>Cardiomyopathies</mesh_term>
      <mesh_term>Cardiomyopathy, Dilated</mesh_term>
      <mesh_term>Heart Failure, Systolic</mesh_term>
      <mesh_term>Ventricular Remodeling</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05973591
  org study id: 4-2022-1665
  nct id: NCT05973591
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  In non-ischemic dilated cardiomyopathy (NIDCM), left ventricular reverse remodeling (LVRR)
        can be achieved through guideline-directed medical therapy (GDMT). LVRR is defined as an
        increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure
        patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% at
        follow-up, which is classified as heart failure with improved EF (HFimpEF) according to
        current guidelines. Several studies have examined the prevalence and predictors of LVRR in
        NIDCM. However, there is a lack of research on LVRR in the context of contemporary
        pharmacotherapy. Studies have demonstrated the beneficial effects of ivabradine in heart
        failure with reduced ejection fraction (HFrEF), improving patients' prognosis. A sub-study of
        the SHIFT trial indicated that ivabradine may also contribute to cardiac remodeling reversal
        in patients with HFrEF. However, there is limited evidence exploring the relationship between
        ivabradine and LVRR, particularly in the context of NIDCM.
  
        Consequently, this study is a retrospective, multi-center cohort study aiming to evaluate the
        impact of ivabradine on LVRR in patients with NIDCM in the current era of medical therapy.
        Furthermore, by conducting this study, we aim to gain insights into the potential role of
        ivabradine in promoting LVRR in NIDCM patients receiving contemporary drug therapy.
  observational model: Cohort
  time perspective: Retrospective
  measure: Prevalence of of LVRR in patients with NIDCM
  time frame: at 12 months after the initiation of GDMT
  description: LVRR is characterized by an increase in left ventricular ejection fraction (LVEF) of more than 10% in heart failure patients with a baseline LVEF of 40% or less, or an increase in LVEF of more than 40% during follow-up, which is classified as heart failure with improved EF (HFimpEF). Furthermore, the initiation of guideline-directed medical therapy (GDMT) is defined as the timeframe for commencing treatment with an angiotensin-converting enzyme inhibitor (ACEi), angiotensin II receptor antagonist (ARB), or beta-blocker after the diagnosis of heart failure with reduced ejection fraction (HFrEF).
  measure: Prevalence of LVRR in NIDCM at 8 months after initiation of GDMT
  time frame: at 8 months after GDMT initiation
  measure: Extent of LVRR (measured by LVEDD/LVESD, LAVI, E/e' in echocardiography) in NIDCM at 8 and 12 months after GDMT initiation
  time frame: at 8 and 12 months after GDMT initiation
  measure: Clinical course of LVRR in NIDCM
  time frame: at 8 and 12 months after GDMT initiation
  measure: Effect of targeted HR (HF <60 or 70/min) on LVRR in NIDCM at 8 and 12 months after GDMT initiation
  time frame: at 8 and 12 months after GDMT initiation
  measure: Effect of degree of change in HR before and after GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation
  time frame: at 8 and 12 months after GDMT initiation
  measure: Impact of GDMT on LVRR in NIDCM at 8 and 12 months after GDMT initiation
  time frame: at 8 and 12 months after GDMT initiation
  measure: Prevalence of symptomatic bradycardia, syncope, or any other adverse events with Ivabradine
  time frame: at 8 and 12 months after GDMT initiation
  arm group label: achieved HR ≥ 70 bpm without ivabradine
  description: **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
  arm group label: achieved HR < 70 bpm without ivabradine
  description: **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
  arm group label: achieved HR ≥ 70 bpm with ivabradine
  description: **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
  arm group label: achieved HR < 70 bpm with ivabradine
  description: **Achieved HR : heart rate (HR) at 12 month follow up after the initiation of GDMT**
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Seok-Min Kang
  role: Principal Investigator
  affiliation: Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
  facility: 
  country: Korea, Republic of
  responsible party type: Sponsor
  mesh term: Cardiomyopathies
  mesh term: Cardiomyopathy, Dilated
  mesh term: Heart Failure, Systolic
  mesh term: Ventricular Remodeling
  sharing ipd: No