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/NCT05976893</url>
    </required_header>
    <id_info>
      <org_study_id>PICVDAC</org_study_id>
      <nct_id>NCT05976893</nct_id>
    </id_info>
    <brief_title>Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer</brief_title>
    <official_title>Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Xiang Xie</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Xinjiang Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Xinjiang Medical University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a prospective, randomized, open-label, and single center trial. To evaluate the&#xD;
        effect of treatment with PCSK9 inhibitor on the risk for cardiovascular death, recurrent&#xD;
        unstable angina, myocardial infarction, stroke, or coronary revascularization in patients&#xD;
        with very high risk of atherosclerotic cardiovascular disease (ASCVD) and cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Subjects will be randomly assigned in a 1:1 ratio to receive subcutaneous injections of PCSK9&#xD;
        inhibitor (evolocumab:420 mg every 4 weeks) plus moderate intensity statin therapy or the&#xD;
        statin alone therapy. After randomization, patients will come to the hospital every 4 weeks&#xD;
        to collect relevant laboratory results and clinical outcomes, and be detected by&#xD;
        echocardiography and carotid ultrasound every 12 weeks until the end of follow-up at week 48&#xD;
        or the occurrence of an endpoint event. The entire study is expected to be conducted for 3&#xD;
        years, with a recruitment period of 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 4</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>
      <intervention_model_description>patients with very high risk of ASCVD and cancer</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Major cardiovascular adverse events</measure>
      <time_frame>From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks</time_frame>
      <description>Major cardiovascular adverse events include cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, and coronary revascularization</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>All cause death</measure>
      <time_frame>From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks</time_frame>
      <description>All cause death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite end points</measure>
      <time_frame>From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks</time_frame>
      <description>Composite end points include cardiogenic shock, cardiac arrest, malignant arrhythmia, heart failure, Non-coronary revascularization</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The compliance rate of lipid control</measure>
      <time_frame>From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks</time_frame>
      <description>Main indicator: LDL-C decreased to below 1.4 mmol/L and decreased by more than 50% from baseline; secondary indicator: non HDL-C&lt;2.2 mmol/L;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The changes of carotid plaque</measure>
      <time_frame>From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks</time_frame>
      <description>By carotid ultrasound</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">620</enrollment>
    <condition>ASCVD</condition>
    <condition>Atherosclerotic Cardiovascular Disease</condition>
    <condition>Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor</condition>
    <condition>Cancer</condition>
    <arm_group>
      <arm_group_label>the PCSK9 inhibitor plus statin therapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily and evolocumab (420 mg) every 4 weeks throughout the study period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>the statin alone therapy</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily throughout the study period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Evolocumab</intervention_name>
      <description>Evolocuma:420 mg every 4 weeks</description>
      <arm_group_label>the PCSK9 inhibitor plus statin therapy</arm_group_label>
      <other_name>Repatha</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Statin</intervention_name>
      <description>The moderate intensity statins used during the study are one of atorvastatin 10-20mg qd, resuvastatin 5-10mg qd, and xuezhikang 0.6g bid (statin intolerance).</description>
      <arm_group_label>the PCSK9 inhibitor plus statin therapy</arm_group_label>
      <arm_group_label>the statin alone therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female ≥ 18 to ≤ 80 years of age&#xD;
  &#xD;
            -  Patients with very high risk of ASCVD (with any of the following):&#xD;
  &#xD;
                 1. Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD&#xD;
                    includes previous acute coronary syndrome (ACS), stable angina, coronary&#xD;
                    revascularization (percutaneous coronary intervention, coronary artery bypass&#xD;
                    graft, and other arterial revascularization procedures), stroke and transient&#xD;
                    ischemic attack (TIA), and peripheral arterial disease. Unequivocally documented&#xD;
                    ASCVD on imaging includes those findings that are known to be predictive of&#xD;
                    clinical events, such as significant plaque on coronary angiography or computed&#xD;
                    tomography (CT) scan (multivessel coronary disease with two major epicardial&#xD;
                    arteries having &gt;50% stenosis), or on carotid ultrasound.&#xD;
  &#xD;
                 2. Diabetes mellitus (DM) with target organ damage, or at least three major risk&#xD;
                    factors, or early onset of type 1 diabetes mellitus (T1DM) of long duration (&gt;20&#xD;
                    years).&#xD;
  &#xD;
            -  Patients have been diagnosed with cancer through histopathology and have a life&#xD;
               expectancy of more than 1 year&#xD;
  &#xD;
            -  Fasting low-density lipoprotein cholesterol (LDL-C) ≥ 1.8 mmol/L or non-high-density&#xD;
               lipoprotein cholesterol (non HDL-C) &gt; 2.6 mmol/L&#xD;
  &#xD;
            -  Participate voluntarily and sign an informed consent&#xD;
  &#xD;
            -  Negative serum Pregnancy test (in women with fertility potential)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant and lactating women&#xD;
  &#xD;
            -  During the study period and within 3 months of receiving the last dose of the study&#xD;
               drug, women with fertility intentions and men unwilling to use effective contraceptive&#xD;
               methods&#xD;
  &#xD;
            -  New York Heart Association (NYHA) class III or IV, or last known left ventricular&#xD;
               ejection fraction &lt; 30%&#xD;
  &#xD;
            -  Uncontrolled hypertension, defined as systolic blood pressure ≥ 180 mmHg and/or&#xD;
               diastolic blood pressure ≥ 110 mmHg&#xD;
  &#xD;
            -  Plan for coronary revascularization or other cardiac surgery in recent (within 3&#xD;
               months after randomization)&#xD;
  &#xD;
            -  Severe renal insufficiency, defined as estimated glomerular filtration rate (eGRF) &lt;&#xD;
               30ml/min/1.73m2 or Serum creatinine (Scr) &gt; 221 umol/L&#xD;
  &#xD;
            -  Severe liver dysfunction, defined as an increase in alanine aminotransferase (ALT) or&#xD;
               aspartate aminotransferase (AST) more than 3 times above the upper limit of normal&#xD;
  &#xD;
            -  Have used PCSK9 inhibitors within 3 months before enrollment, or have a history of&#xD;
               severe allergic reactions to PCSK9 inhibitors&#xD;
  &#xD;
            -  Severe infections requiring intravenous antibiotics&#xD;
  &#xD;
            -  HIV-positive or history of acquired immunodeficiency syndrome (AIDS)&#xD;
  &#xD;
            -  With cognitive impairment or psychiatric illnesses&#xD;
  &#xD;
            -  Participating in other trials&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Xiang Xie, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Affiliated Hospital of Xinjiang Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xiang Xie, PhD</last_name>
      <phone>+869914366892</phone>
      <email>xiangxie999@sina.com</email>
    </overall_contact>
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    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Xinjiang Medical University</investigator_affiliation>
      <investigator_full_name>Xiang Xie</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>ASCVD</keyword>
    <keyword>cancer</keyword>
    <keyword>PCSK9</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>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/NCT05976893
  org study id: PICVDAC
  nct id: NCT05976893
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This study is a prospective, randomized, open-label, and single center trial. To evaluate the
        effect of treatment with PCSK9 inhibitor on the risk for cardiovascular death, recurrent
        unstable angina, myocardial infarction, stroke, or coronary revascularization in patients
        with very high risk of atherosclerotic cardiovascular disease (ASCVD) and cancer.
  Subjects will be randomly assigned in a 1:1 ratio to receive subcutaneous injections of PCSK9
        inhibitor (evolocumab:420 mg every 4 weeks) plus moderate intensity statin therapy or the
        statin alone therapy. After randomization, patients will come to the hospital every 4 weeks
        to collect relevant laboratory results and clinical outcomes, and be detected by
        echocardiography and carotid ultrasound every 12 weeks until the end of follow-up at week 48
        or the occurrence of an endpoint event. The entire study is expected to be conducted for 3
        years, with a recruitment period of 2 years.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: patients with very high risk of ASCVD and cancer
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Major cardiovascular adverse events
  time frame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
  description: Major cardiovascular adverse events include cardiovascular death, recurrent unstable angina, myocardial infarction, stroke, and coronary revascularization
  measure: All cause death
  time frame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
  description: All cause death
  measure: Composite end points
  time frame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
  description: Composite end points include cardiogenic shock, cardiac arrest, malignant arrhythmia, heart failure, Non-coronary revascularization
  measure: The compliance rate of lipid control
  time frame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
  description: Main indicator: LDL-C decreased to below 1.4 mmol/L and decreased by more than 50% from baseline; secondary indicator: non HDL-C<2.2 mmol/L;
  measure: The changes of carotid plaque
  time frame: From date of randomization until the date of first documented endpoint or date of completion of follow-up, whichever came first, assessed up to 48 weeks
  description: By carotid ultrasound
  arm group label: the PCSK9 inhibitor plus statin therapy
  arm group type: Experimental
  description: Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily and evolocumab (420 mg) every 4 weeks throughout the study period.
  arm group label: the statin alone therapy
  arm group type: Other
  description: Patients with very high risk of ASCVD and cancer are treated with moderate intensity statin daily throughout the study period.
  intervention type: Drug
  intervention name: Evolocumab
  description: Evolocuma:420 mg every 4 weeks
  arm group label: the PCSK9 inhibitor plus statin therapy
  other name: Repatha
  intervention type: Drug
  intervention name: Statin
  description: The moderate intensity statins used during the study are one of atorvastatin 10-20mg qd, resuvastatin 5-10mg qd, and xuezhikang 0.6g bid (statin intolerance).
  arm group label: the PCSK9 inhibitor plus statin therapy
  arm group label: the statin alone therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Xiang Xie, PhD
  role: Principal Investigator
  affiliation: First Affiliated Hospital of Xinjiang Medical University
  last name: Xiang Xie, PhD
  phone: +869914366892
  email: xiangxie999@sina.com
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  responsible party type: Sponsor-Investigator
  investigator affiliation: Xinjiang Medical University
  investigator full name: Xiang Xie
  investigator title: Principal Investigator
  mesh term: Cardiovascular Diseases
  mesh term: Atherosclerosis
  mesh term: Evolocumab
  sharing ipd: No