<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/NCT03273387</url>
  </required_header>
  <id_info>
    <org_study_id>LB.02.01/VII/172/KEP.009/2017</org_study_id>
    <nct_id>NCT03273387</nct_id>
  </id_info>
  <brief_title>The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension</brief_title>
  <acronym>TRIMETA-PH</acronym>
  <official_title>The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension Patients in National Cardiovascular Center Harapan Kita Hospital Indonesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indonesia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indonesia University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The study will evaluate the effect of trimetazidine versus placebo in addition to standard&#xD;
      pulmonary arterial hypertension regime on right ventricular function in pulmonary arterial&#xD;
      hypertension patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Right ventricular dysfunction is the worst mortality predictor in pulmonary arterial&#xD;
      hypertension (PAH). Recent study has described that approximately 25% of PAH patients will&#xD;
      developed into right ventricular failure despite therapeutic reduction of pulmonary vascular&#xD;
      resistance. Subsequently, several studies have shown that fatty acid accumulation in right&#xD;
      ventricle was inversely correlated with right ventricular function in PAH patients. Several&#xD;
      PAH animal studies have revealed that metabolic glucose oxidation impairment through&#xD;
      increased aerobic glycolysis, mitochondrial dysfunction, and lipotoxicity play significant&#xD;
      role in right ventricular failure. Moreover, several pulmonary hypertension animal studies&#xD;
      have demonstrated the benefit of partial fatty acid inhibitor such as trimetazidine on right&#xD;
      ventricle function. It was hypothesize that trimetazidine improved right ventricular function&#xD;
      through indirect effect of increased glucose oxidation by blocking the Randle cycle.&#xD;
      Therefore, we hypothesize that trimetazidine can improve right ventricular function in&#xD;
      pulmonary arterial hypertension patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 10, 2017</start_date>
  <completion_date type="Actual">December 14, 2018</completion_date>
  <primary_completion_date type="Actual">November 1, 2018</primary_completion_date>
  <phase>Phase 2/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>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention</measure>
    <time_frame>Baseline and 3 months after intervention</time_frame>
    <description>Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Cardiac Fibrosis After 3 Months Intervention</measure>
    <time_frame>Baseline and 3 months after intervention</time_frame>
    <description>Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Functional Capacity After 3 Month Intervention</measure>
    <time_frame>Baseline and 3 months after intervention</time_frame>
    <description>Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline.&#xD;
SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Precapillary Pulmonary Hypertension</condition>
  <arm_group>
    <arm_group_label>Sugar pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trimetazidine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimetazidine</intervention_name>
    <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
    <arm_group_label>trimetazidine</arm_group_label>
    <other_name>Trizedon MR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
    <arm_group_label>Sugar pill</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pre-capillary Pulmonary Hypertension patients assessed by right heart catheterization&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient belonging to post-capillary, Isolated post-capillary, or combined post&#xD;
             -capillary and pre-capillary pulmonary hypertension according to 2015 ESC/ERS&#xD;
             Guidelines for the diagnosis and treatment of pulmonary hypertension.&#xD;
&#xD;
          -  Moderate to severe chronic pulmonary obstructive disease&#xD;
&#xD;
          -  Right Ventricular Ejection Fraction &gt; 45% assessed by cardiac magnetic resonance.&#xD;
&#xD;
          -  Documented left ventricular dysfunction with left ventricular ejection fraction &lt; 50%&#xD;
             assessed by cardiac magnetic resonance.&#xD;
&#xD;
          -  Severe renal impairment (Serum creatinine &gt; 2.5 mg/dL, eGFR &lt; 30ml/min/1.73 m^2, or&#xD;
             routine dialysis treatment).&#xD;
&#xD;
          -  Malignant arrhythmia such as total atrioventricular block or ventricular fibrillation&#xD;
             or unstable ventricular tachycardia.&#xD;
&#xD;
          -  Patients who are receiving or have been receiving any investigational drugs within 1&#xD;
             month before the baseline visit&#xD;
&#xD;
          -  Acute or chronic impairment (other than dyspnea) limiting the ability to comply with&#xD;
             study requirements&#xD;
&#xD;
          -  Psychotic, addictive or other disorder limiting the ability to provide informed&#xD;
             consent or to comply with study requirements&#xD;
&#xD;
          -  Females who are lactating or pregnant or those who plan to become pregnant during the&#xD;
             study&#xD;
&#xD;
          -  Known Parkinson disease&#xD;
&#xD;
          -  Known hypersensitivity to any of the drug formulation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hary Sakti Muliawan, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department Cardiology and Vascular Medicine Universitas Indonesia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cardiovascular Center Harapan Kita Hospital</name>
      <address>
        <city>Jakarta</city>
        <zip>11420</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 3, 2017</study_first_submitted>
  <study_first_submitted_qc>September 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <results_first_submitted>March 6, 2019</results_first_submitted>
  <results_first_submitted_qc>September 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 3, 2019</results_first_posted>
  <last_update_submitted>September 11, 2019</last_update_submitted>
  <last_update_submitted_qc>September 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indonesia University</investigator_affiliation>
    <investigator_full_name>Hary Sakti Muliawan, MD, PhD</investigator_full_name>
    <investigator_title>MD,PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trimetazidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03273387/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03273387/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from NCCHK PH outpatient clinic from September 2017 until November 2018</recruitment_details>
      <pre_assignment_details>A total of 35 Patients were enrolled between September 2017 and November 2018 at NCCHK PAH outpatient clinic. A total of 26 patients were consent to underwent the trial and randomly assigned to receive trimetazidine or placebo with ratio 1:1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sugar Pill</title>
          <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
        <group group_id="P2">
          <title>Trimetazidine</title>
          <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sugar Pill</title>
          <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
        <group group_id="B2">
          <title>Trimetazidine</title>
          <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47" spread="3.8"/>
                    <measurement group_id="B2" value="48" spread="1.5"/>
                    <measurement group_id="B3" value="48" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Percentage of gender differences in our PAH patients.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>onset of diagnosis to study</title>
          <description>The number of days since first diagnosed with PAH until intervention. The longer the onset of diagnosis to study intervention suggest longer the patients suffered from PAH which may or may not correlated with PAH severity</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1170" spread="387"/>
                    <measurement group_id="B2" value="926" spread="214"/>
                    <measurement group_id="B3" value="1048" spread="1093"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SF-36 Functional Capacity</title>
          <description>SF-36 functional capacity score is an questionnaire instrument which evaluate quality of life including functional capacity. The SF-36 functional capacity score scale from 0-100 with better functional capacity along with higher scale.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.15" spread="4.77"/>
                    <measurement group_id="B2" value="46.54" spread="5.44"/>
                    <measurement group_id="B3" value="53.84" spread="19.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>WHO Functional Class</title>
          <description>Percentage of participant with WHO functional class II or III on each group. WHO functional class II defines as PAH patients with slight limitation of physical activity. They are comfortable at rest. Ordinary activity causes dyspnea, fatigue, chest pain, or syncope.&#xD;
WHO functional class III defines as PAH patients with marked limitation of physical activity. They are comfortable with rest. Less than ordinary activities causes dyspnea, fatigue, chest pain or syncope.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>WHO functional class II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>WHO functional class III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Glomerular Filtration Rate</title>
          <units>ml/min/1.73 m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="96.6" spread="7.9"/>
                    <measurement group_id="B2" value="110.7" spread="3.9"/>
                    <measurement group_id="B3" value="106" spread="15.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.3" spread="3.8"/>
                    <measurement group_id="B2" value="21" spread="0.8"/>
                    <measurement group_id="B3" value="22.1" spread="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Phosphodiesterase-5 inhibitor</title>
          <description>Percentage of participant with Phosphodiesterase-5 inhibitor treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prostacyclin analogue (beraprost)</title>
          <description>Percentage of participants with oral prostacyclin analogue (beraprost) treatment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>beta blocker</title>
          <description>Percentage of participant with beta blocker treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ACE-inhibitor</title>
          <description>Percentage of participant with ACE-Inhibitor treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Angiotensin receptor II blocker</title>
          <description>Percentage of participant with Angiotensin receptor II blocker treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Warfarin</title>
          <description>Percentage of participant with warfarin treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>spironolactone</title>
          <description>Percentage of participant with spironolactone treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>furosemide</title>
          <description>Percentage of participant with furosemide treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>digoxin</title>
          <description>Percentage of participant with digoxin treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>mean Right atrial pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.9" spread="1.4"/>
                    <measurement group_id="B2" value="6" spread="1.2"/>
                    <measurement group_id="B3" value="5.9" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>mean pulmonary arterial pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="5.9"/>
                    <measurement group_id="B2" value="59" spread="3.6"/>
                    <measurement group_id="B3" value="60" spread="11.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LV end diastolic pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.2" spread="1.2"/>
                    <measurement group_id="B2" value="7.8" spread="0.8"/>
                    <measurement group_id="B3" value="7.4" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>RV end diastolic volume</title>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="258" spread="28"/>
                    <measurement group_id="B2" value="260" spread="31"/>
                    <measurement group_id="B3" value="259" spread="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>RV end systolic volume</title>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="193" spread="20"/>
                    <measurement group_id="B2" value="206" spread="25"/>
                    <measurement group_id="B3" value="197" spread="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>RV ejection fraction</title>
          <units>%</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.5" spread="2.8"/>
                    <measurement group_id="B2" value="21.1" spread="4.4"/>
                    <measurement group_id="B3" value="22.4" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LV end diastolic volume</title>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79" spread="6.3"/>
                    <measurement group_id="B2" value="83" spread="5.3"/>
                    <measurement group_id="B3" value="81" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LV end systolic volume</title>
          <units>ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29" spread="2.8"/>
                    <measurement group_id="B2" value="33" spread="3.3"/>
                    <measurement group_id="B3" value="31" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LV ejection fraction</title>
          <units>%</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" spread="2.6"/>
                    <measurement group_id="B2" value="59" spread="2.4"/>
                    <measurement group_id="B3" value="62" spread="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Native T1 anteroseptal</title>
          <description>Native T1 is measuring the T1 tissue using CMR with MOLLI technique at 1.5 T which normal value ranged between 900 to 1100ms.&#xD;
Native T1 is increased in edema, inflammation, cellular edema, myocyte necrosis, and fibrosis.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="993" spread="612"/>
                    <measurement group_id="B2" value="1354" spread="441"/>
                    <measurement group_id="B3" value="1164" spread="555"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Native T1 septal</title>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1108" spread="512"/>
                    <measurement group_id="B2" value="1110" spread="411"/>
                    <measurement group_id="B3" value="1109" spread="454"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Native T1 inferoseptal</title>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="930" spread="418"/>
                    <measurement group_id="B2" value="1474" spread="736"/>
                    <measurement group_id="B3" value="1187" spread="637"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Native T1 Lateral</title>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1090" spread="470"/>
                    <measurement group_id="B2" value="1357" spread="473"/>
                    <measurement group_id="B3" value="1216" spread="478"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention</title>
        <description>Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.</description>
        <time_frame>Baseline and 3 months after intervention</time_frame>
        <population>A total 13 patients were assigned to each group equally. There were 6 patients who were not able to complete the study. A total of 2 patients from both group died due to RV failure. One patients from trimetazidine group withdrawn due to atypical angina and one patients from placebo group withdrawn due to claustrophobia.</population>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
          <group group_id="O2">
            <title>Trimetazidine</title>
            <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention</title>
          <description>Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.</description>
          <population>A total 13 patients were assigned to each group equally. There were 6 patients who were not able to complete the study. A total of 2 patients from both group died due to RV failure. One patients from trimetazidine group withdrawn due to atypical angina and one patients from placebo group withdrawn due to claustrophobia.</population>
          <units>percentage of ejected blood</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.8" spread="1.6"/>
                    <measurement group_id="O2" value="3.9" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.008</p_value>
            <p_value_desc>95% Confidence interval 1.97 - 11.3 statistical significant if p&lt;0.05</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>t=2.988 df=18</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Cardiac Fibrosis After 3 Months Intervention</title>
        <description>Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.</description>
        <time_frame>Baseline and 3 months after intervention</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
          <group group_id="O2">
            <title>Trimetazidine</title>
            <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Cardiac Fibrosis After 3 Months Intervention</title>
          <description>Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Native T1 anteroseptal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="138" spread="555"/>
                    <measurement group_id="O2" value="190" spread="538"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native T1 Septal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="292" spread="677"/>
                    <measurement group_id="O2" value="371" spread="670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native T1 Inferoseptal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="294" spread="618"/>
                    <measurement group_id="O2" value="-123" spread="645"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native T1 Lateral</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="287" spread="744"/>
                    <measurement group_id="O2" value="-194" spread="487"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.33</p_value>
            <p_value_desc>statistical significant if p &lt;0.05</p_value_desc>
            <method>two-way ANOVA</method>
            <method_desc>DF=3</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Functional Capacity After 3 Month Intervention</title>
        <description>Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline.&#xD;
SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.</description>
        <time_frame>Baseline and 3 months after intervention</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Pill</title>
            <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
          <group group_id="O2">
            <title>Trimetazidine</title>
            <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Functional Capacity After 3 Month Intervention</title>
          <description>Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline.&#xD;
SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.73" spread="3.72"/>
                    <measurement group_id="O2" value="11.5" spread="5.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>95% Confidence interval 15.92 to 42.53 statistical significant if p &lt;0.05</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>t=4.598 df=19</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>three months for each intervention.</time_frame>
      <desc>safety population included all participants who received at least one dose of intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sugar Pill</title>
          <description>The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.&#xD;
Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
        <group group_id="E2">
          <title>Trimetazidine</title>
          <description>The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.&#xD;
Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiovascular mortality</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>musculoskeletal angina</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>dr. Bambang WIdyantoro, FIHA, PhD</name_or_title>
      <organization>Department of Cardiology and Vascular Medicine, Universitas Indonesia</organization>
      <phone>+628128164299</phone>
      <email>bambang_ui@yahoo.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03273387
org study id: LB.02.01/VII/172/KEP.009/2017
nct id: NCT03273387
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study will evaluate the effect of trimetazidine versus placebo in addition to standard
      pulmonary arterial hypertension regime on right ventricular function in pulmonary arterial
      hypertension patients.
Right ventricular dysfunction is the worst mortality predictor in pulmonary arterial
      hypertension (PAH). Recent study has described that approximately 25% of PAH patients will
      developed into right ventricular failure despite therapeutic reduction of pulmonary vascular
      resistance. Subsequently, several studies have shown that fatty acid accumulation in right
      ventricle was inversely correlated with right ventricular function in PAH patients. Several
      PAH animal studies have revealed that metabolic glucose oxidation impairment through
      increased aerobic glycolysis, mitochondrial dysfunction, and lipotoxicity play significant
      role in right ventricular failure. Moreover, several pulmonary hypertension animal studies
      have demonstrated the benefit of partial fatty acid inhibitor such as trimetazidine on right
      ventricle function. It was hypothesize that trimetazidine improved right ventricular function
      through indirect effect of increased glucose oxidation by blocking the Randle cycle.
      Therefore, we hypothesize that trimetazidine can improve right ventricular function in
      pulmonary arterial hypertension patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention
time frame: Baseline and 3 months after intervention
description: Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.
measure: Changes in Cardiac Fibrosis After 3 Months Intervention
time frame: Baseline and 3 months after intervention
description: Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.
measure: Changes in Functional Capacity After 3 Month Intervention
time frame: Baseline and 3 months after intervention
description: Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline.
SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.
arm group label: Sugar pill
arm group type: Placebo Comparator
description: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
arm group label: trimetazidine
arm group type: Experimental
description: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
intervention type: Drug
intervention name: Trimetazidine
description: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
arm group label: trimetazidine
other name: Trizedon MR
intervention type: Drug
intervention name: Placebo oral capsule
description: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.
arm group label: Sugar pill
other name: sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hary Sakti Muliawan, MD,PhD
role: Principal Investigator
affiliation: Department Cardiology and Vascular Medicine Universitas Indonesia
facility: 
country: Indonesia
responsible party type: Principal Investigator
investigator affiliation: Indonesia University
investigator full name: Hary Sakti Muliawan, MD, PhD
investigator title: MD,PhD
mesh term: Hypertension, Pulmonary
mesh term: Pulmonary Arterial Hypertension
mesh term: Hypertension
mesh term: Trimetazidine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 