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/NCT05974345</url>
    </required_header>
    <id_info>
      <org_study_id>CKJX839B1FR01</org_study_id>
      <nct_id>NCT05974345</nct_id>
    </id_info>
    <brief_title>In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in French Patients With Established Cardiovascular Disease</brief_title>
    <official_title>In Silico Non Interventional Secondary Use of Data Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in French Patients With Established Cardiovascular Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novartis Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Novartis</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>
        Study CKJX839B1FR01 in an In silico trial to predict the efficacy of Inclisiran therapy on&#xD;
        major adverse cardiovascular events (MACE) and cardiovascular (CV) death in French virtual&#xD;
        patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Purpose of this study is to predict the size of efficacy of inclisiran 300 mg s.c.,&#xD;
        administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in addition to&#xD;
        currently available lipid lowering therapies (LLTs) on a 3-Point-Major Adverse Cardiovascular&#xD;
        Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) or&#xD;
        non-fatal ischemic stroke, and on CV death, in a secondary prevention French cohort of ASCVD&#xD;
        virtual patients with a LDL-C ≥ 70 mg/dL. This will be compared to 1) placebo in adjunct to&#xD;
        high-intensity statin therapy with or without ezetimibe, 2) ezetimibe in adjunct to&#xD;
        high-intensity statin therapy, 3) Evolocumab in adjunct to high-intensity statin therapy and&#xD;
        ezetimibe.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 20, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">October 16, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Other</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Time to the first occurrence between trial start and end of follow-up of any component of 3P-MACE (composite of CV death, non-fatal MI or non-fatal ischemic stroke)</measure>
      <time_frame>5 years of follow-up</time_frame>
      <description>3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time to the first occurrence between trial start and end of follow-up of CV death</measure>
      <time_frame>5 years of follow-up</time_frame>
      <description>CV death is defined as death due to cardiovascular events</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)</measure>
      <time_frame>5 years of follow-up</time_frame>
      <description>Myocardial infarction (MI)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)</measure>
      <time_frame>5 years of follow-up</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE)</measure>
      <time_frame>5 years of follow-up</time_frame>
      <description>MALE include acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in LDL-C from baseline to specified time points</measure>
      <time_frame>baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.</time_frame>
      <description>Low density lipoprotein cholesterol (LDL-C)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time adjusted percentage change in LDL-C</measure>
      <time_frame>From baseline between Day 90 and the end of follow-up period (up to 5 years)</time_frame>
      <description>This is the average percentage change in LDL-C from baseline over period from Day 90 and the end of follow-up period.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">54724</enrollment>
    <condition>Atherosclerotic Cardiovascular Disease</condition>
    <arm_group>
      <arm_group_label>Virtual Patient with ASCVD</arm_group_label>
      <description>Virtual Patient with ASCVD and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe. Each virtual patient is his own control.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Inclisiran sodium</intervention_name>
      <description>Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.</description>
      <arm_group_label>Virtual Patient with ASCVD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.</description>
      <arm_group_label>Virtual Patient with ASCVD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ezetimibe</intervention_name>
      <description>Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.</description>
      <arm_group_label>Virtual Patient with ASCVD</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Evolocumab</intervention_name>
      <description>Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.</description>
      <arm_group_label>Virtual Patient with ASCVD</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Virtual Patient with ASCVD (previous MI, previous ischemic stroke, previous peripheral&#xD;
          arterial disease) and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity&#xD;
          statin with or without ezetimibe.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria :&#xD;
  &#xD;
            1. Patients with atherosclerotic CV disease, defined as any of the following&#xD;
  &#xD;
               i. Previous MI&#xD;
  &#xD;
               ii. Previous ischemic stroke&#xD;
  &#xD;
               iii. Previous symptomatic peripheral arterial disease (PAD) as evidenced by either&#xD;
               intermittent claudication with ABI &lt;0.85, prior peripheral arterial revascularization&#xD;
               procedure, or amputation due to atherosclerotic disease&#xD;
  &#xD;
            2. Fasting LDL-C ≥ 70 mg/dL&#xD;
  &#xD;
            3. Under stable (≥ 4 weeks) well-tolerated high-intensity statin with or without&#xD;
               ezetimibe.&#xD;
  &#xD;
          Exclusion Criteria :&#xD;
  &#xD;
          Patients with acute coronary syndrome, ischemic stroke, peripheral arterial&#xD;
          revascularization procedure or amputation due to atherosclerotic disease &lt;4 weeks prior to&#xD;
          the first study visit&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Novartis Pharmaceuticals</last_name>
      <role>Study Director</role>
      <affiliation>Novartis Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Atherosclerotic cardiovascular disease</keyword>
    <keyword>Hypercholesterolemia</keyword>
    <keyword>Dyslipidemia</keyword>
    <keyword>High cholesterol</keyword>
    <keyword>Hyperlipidemia</keyword>
    <keyword>Inclisiran</keyword>
    <keyword>siRNA</keyword>
    <keyword>KJX839</keyword>
    <keyword>Myocardial infarction</keyword>
    <keyword>Ischemic stroke</keyword>
    <keyword>Peripheral arterial disease</keyword>
    <keyword>In silico model</keyword>
    <keyword>In silico simulation</keyword>
    <keyword>PCSK9 inhibitors</keyword>
    <keyword>Arteriosclerosis</keyword>
    <keyword>Atherosclerosis</keyword>
    <keyword>Arterial Occlusive Diseases</keyword>
    <keyword>Vascular Diseases</keyword>
    <keyword>Cardiovascular Diseases</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cardiovascular Diseases</mesh_term>
      <mesh_term>Atherosclerosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ezetimibe</mesh_term>
      <mesh_term>Evolocumab</mesh_term>
    </intervention_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/NCT05974345
  org study id: CKJX839B1FR01
  nct id: NCT05974345
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Study CKJX839B1FR01 in an In silico trial to predict the efficacy of Inclisiran therapy on
        major adverse cardiovascular events (MACE) and cardiovascular (CV) death in French virtual
        patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C.
  Purpose of this study is to predict the size of efficacy of inclisiran 300 mg s.c.,
        administered on Day 1, Month 3 (Day 90), and every 6 months thereafter in addition to
        currently available lipid lowering therapies (LLTs) on a 3-Point-Major Adverse Cardiovascular
        Events (3P-MACE) defined as a composite of CV death, non-fatal myocardial infarction (MI) or
        non-fatal ischemic stroke, and on CV death, in a secondary prevention French cohort of ASCVD
        virtual patients with a LDL-C ≥ 70 mg/dL. This will be compared to 1) placebo in adjunct to
        high-intensity statin therapy with or without ezetimibe, 2) ezetimibe in adjunct to
        high-intensity statin therapy, 3) Evolocumab in adjunct to high-intensity statin therapy and
        ezetimibe.
  observational model: Other
  time perspective: Other
  measure: Time to the first occurrence between trial start and end of follow-up of any component of 3P-MACE (composite of CV death, non-fatal MI or non-fatal ischemic stroke)
  time frame: 5 years of follow-up
  description: 3P-MACE is a confirmed composite endpoint which includes cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.
  measure: Time to the first occurrence between trial start and end of follow-up of CV death
  time frame: 5 years of follow-up
  description: CV death is defined as death due to cardiovascular events
  measure: Time to the first occurrence between trial start and end of follow-up of MI (non-fatal or fatal)
  time frame: 5 years of follow-up
  description: Myocardial infarction (MI)
  measure: Time to the first occurrence between trial start and end of follow-up of ischemic stroke (non-fatal or fatal)
  time frame: 5 years of follow-up
  measure: Time to the first occurrence between trial start and end of follow-up of Major Adverse Limb events (MALE)
  time frame: 5 years of follow-up
  description: MALE include acute lower limb ischemia, lower limb amputation due to ischemia, or urgent lower limb revascularization for ischemia
  measure: Change in LDL-C from baseline to specified time points
  time frame: baseline, day 1, 30, 90 and every 6 months afterwards will be presented and additional time points could be added if deemed necessary.
  description: Low density lipoprotein cholesterol (LDL-C)
  measure: Time adjusted percentage change in LDL-C
  time frame: From baseline between Day 90 and the end of follow-up period (up to 5 years)
  description: This is the average percentage change in LDL-C from baseline over period from Day 90 and the end of follow-up period.
  arm group label: Virtual Patient with ASCVD
  description: Virtual Patient with ASCVD and LDL-C ≥ 70 mg/dL despite receiving a well-tolerated high-intensity statin with or without ezetimibe. Each virtual patient is his own control.
  intervention type: Drug
  intervention name: Inclisiran sodium
  description: Drug: Inclisiran sodium 300 mg virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.
  arm group label: Virtual Patient with ASCVD
  intervention type: Drug
  intervention name: Placebo
  description: Drug: Placebo virtually subcutaneously administered on Day 1, Month 3 (Day 90) and every 6 months thereafter until end of simulation.
  arm group label: Virtual Patient with ASCVD
  intervention type: Drug
  intervention name: Ezetimibe
  description: Drug: Ezetimibe 10 mg virtually orally once a day until end of simulation.
  arm group label: Virtual Patient with ASCVD
  intervention type: Drug
  intervention name: Evolocumab
  description: Drug: Evolocumab 140 mg virtually subcutaneously administered every two weeks until end of simulation.
  arm group label: Virtual Patient with ASCVD
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  role: Study Director
  affiliation: Novartis Pharmaceuticals
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  responsible party type: Sponsor
  mesh term: Cardiovascular Diseases
  mesh term: Atherosclerosis
  mesh term: Ezetimibe
  mesh term: Evolocumab
  sharing ipd: No