<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/NCT03775070</url>
  </required_header>
  <id_info>
    <org_study_id>201806014MINB</org_study_id>
    <nct_id>NCT03775070</nct_id>
  </id_info>
  <brief_title>Simvastatin Therapy in Patients With Dilated Cardiomyopathy.</brief_title>
  <acronym>SavDCM</acronym>
  <official_title>An Open Label, Single-armed, Exploratory Study of Simvastatin Therapy on the Cardiac Function in Patients With Dilated Cardiomyopathy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated&#xD;
      with significant early morbidity and mortality. About half of patients die or require heart&#xD;
      transplantation within 5 years of diagnosis. The medical therapy for DCM with heart failure&#xD;
      includes anti-congestive medications and antiplatelet therapy. Those who fail to improve&#xD;
      within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive&#xD;
      medications. The investigators had conducted precision-medicine-based approach to provide&#xD;
      strategic approach as drug repurposing to identify new treatments. The investigators have&#xD;
      identified the beneficial effects from a statin, simvastatin, to restore the cardiac&#xD;
      contractility. The investigators would further assess the efficacy of simvastatin to improve&#xD;
      the cardiac function in patients with DCM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated&#xD;
      with significant early morbidity and mortality. About half of patients die or require heart&#xD;
      transplantation within 5 years of diagnosis. The survival advantage from transplantation is&#xD;
      limited, particularly in DCM infants.&#xD;
&#xD;
      The medical therapy for DCM with heart failure includes anti-congestive medications and&#xD;
      antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually&#xD;
      deteriorated even upon aggressive anti-congestive medications. The investigators had&#xD;
      conducted precision-medicine-based approach to provide strategic approach as drug repurposing&#xD;
      to identify new treatments. The investigators have identified the beneficial effects from a&#xD;
      statin, simvastatin, to restore the cardiac contractility in a DCM proband.The initial&#xD;
      experience in the proband is promising.&#xD;
&#xD;
      Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of&#xD;
      patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children,&#xD;
      though the dosage range and the indication remain unclear, it had been used in children with&#xD;
      various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated&#xD;
      with simvastatin had a lower New York Heart Association functional class compared with those&#xD;
      receiving placebo. The LVEF also improved in the simvastatin group. The investigators would&#xD;
      further assess the efficacy of simvastatin to improve the cardiac function in patients with&#xD;
      DCM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Actual">July 31, 2022</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 1st month(The 1st month follow-up time tolerates a 0.5-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.</measure>
    <time_frame>baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.</measure>
    <time_frame>baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v3.0</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>We will check patient's biochemistry profile including, lipid profile, liver function and renal function. Treatment-related adverse events would be assessed by CTCAE v3.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Dilated Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Simvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simvastatin, 0.5mg/kg/d(maximum 20mg), once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>Starting dosage: in adult, the dose of simvastatin is 10 mg once daily. In children, the dose is 0.25mg/Kg/day (maximum dose: 10 mg/d).&#xD;
Target dosage: in adult, the dose of simvastatin is 20 mg once daily. In children, the dose is 0.5mg/Kg/day (maximum dose: 20 mg/d).&#xD;
The basic anti-congestive medication will be kept as the same.&#xD;
The dosage may be titrated to a lesser dose by investigators according to the patient's condition.</description>
    <arm_group_label>Simvastatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who have already received anti-congestive medications for at least three&#xD;
             months and still have compromised LV function (LVEF &lt; 45% and the Z score of the LV&#xD;
             end-diastolic diameter &gt; 2.0).&#xD;
&#xD;
          -  Patients who have persistent or even worsening heart failure after one month of&#xD;
             anti-congestive medications.&#xD;
&#xD;
          -  Patients who have positive family history of dilated cardiomyopathy and have received&#xD;
             anti-congestive medications for one week.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who underwent prior cardiac surgery. Those who received DCM related cardiac&#xD;
             surgery, such as mitral valve plasty, for longer than a year are not subject to this&#xD;
             restriction.&#xD;
&#xD;
          -  Patients who had liver / renal dysfunction.&#xD;
&#xD;
          -  Patients who are pregnant or plan to pregnancy in the period of study.&#xD;
&#xD;
          -  Patients who are intolerance to simvastatin therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simvastatin</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/NCT03775070
org study id: 201806014MINB
nct id: NCT03775070
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated
      with significant early morbidity and mortality. About half of patients die or require heart
      transplantation within 5 years of diagnosis. The medical therapy for DCM with heart failure
      includes anti-congestive medications and antiplatelet therapy. Those who fail to improve
      within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive
      medications. The investigators had conducted precision-medicine-based approach to provide
      strategic approach as drug repurposing to identify new treatments. The investigators have
      identified the beneficial effects from a statin, simvastatin, to restore the cardiac
      contractility. The investigators would further assess the efficacy of simvastatin to improve
      the cardiac function in patients with DCM.
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated
      with significant early morbidity and mortality. About half of patients die or require heart
      transplantation within 5 years of diagnosis. The survival advantage from transplantation is
      limited, particularly in DCM infants.

      The medical therapy for DCM with heart failure includes anti-congestive medications and
      antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually
      deteriorated even upon aggressive anti-congestive medications. The investigators had
      conducted precision-medicine-based approach to provide strategic approach as drug repurposing
      to identify new treatments. The investigators have identified the beneficial effects from a
      statin, simvastatin, to restore the cardiac contractility in a DCM proband.The initial
      experience in the proband is promising.

      Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of
      patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children,
      though the dosage range and the indication remain unclear, it had been used in children with
      various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated
      with simvastatin had a lower New York Heart Association functional class compared with those
      receiving placebo. The LVEF also improved in the simvastatin group. The investigators would
      further assess the efficacy of simvastatin to improve the cardiac function in patients with
      DCM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 1st month(The 1st month follow-up time tolerates a 0.5-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )
measure: Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound.
time frame: baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 6th month(The 6th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 9th month(The 9th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 12th month(The 12th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 15th month(The 15th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 18th month(The 18th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 21st month(The 21th month follow-up time tolerates a 1-month window )
measure: Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level.
time frame: baseline, 24th month(The 24th month follow-up time tolerates a 1-month window )
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v3.0
time frame: Up to 24 months
description: We will check patient's biochemistry profile including, lipid profile, liver function and renal function. Treatment-related adverse events would be assessed by CTCAE v3.0
arm group label: Simvastatin
arm group type: Experimental
description: Simvastatin, 0.5mg/kg/d(maximum 20mg), once daily
intervention type: Drug
intervention name: Simvastatin
description: Starting dosage: in adult, the dose of simvastatin is 10 mg once daily. In children, the dose is 0.25mg/Kg/day (maximum dose: 10 mg/d).
Target dosage: in adult, the dose of simvastatin is 20 mg once daily. In children, the dose is 0.5mg/Kg/day (maximum dose: 20 mg/d).
The basic anti-congestive medication will be kept as the same.
The dosage may be titrated to a lesser dose by investigators according to the patient's condition.
arm group label: Simvastatin
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated
mesh term: Simvastatin
sharing ipd: No