<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/NCT03783351</url>
  </required_header>
  <id_info>
    <org_study_id>GUARANTEE</org_study_id>
    <nct_id>NCT03783351</nct_id>
  </id_info>
  <brief_title>Genotyping GUided Antiplatelet theRapy in pAtieNts Treated With Drug Eluting stEnts (GUARANTEE)</brief_title>
  <official_title>CYP2C19 Genotype-GUided Dual Antiplatelet theRapy in pAtieNts Treated With New Generation Drug Eluting stEnts (the GUARANTEE Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Anzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Anzhen Hospital</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 aim of this study is to assess the efficacy and safety of the CYP2C19 genotype guided&#xD;
      antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19*2 or *3&#xD;
      allele and ticagrelor in carriers of a CYP2C19*2 or *3 allele in patients treated with new&#xD;
      generation drug eluting stents.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: P2Y12 receptor inhibitors are crucial for the management of patients undergoing&#xD;
      coronary stenting. Although large-scale trials have shown that ticagrelor is superior to&#xD;
      clopidogrel in terms of platelet inhibition and reduction of major adverse cardiovascular&#xD;
      events (MACE), clopidogrel remains the most commonly used P2Y12 receptor inhibitor due to its&#xD;
      lower price and bleeding risk. Despite the combined use of aspirin and clopidogrel, a&#xD;
      substantial portion of patients after coronary stenting are at increased risk for adverse&#xD;
      cardiovascular events including death, myocardial infarction, and stent thrombosis. This&#xD;
      phenomenon may be due to the so-called clopidogrel resistance. Cytochrome P450 2C19 (CYP2C19)&#xD;
      polymorphism plays a crucial role in the clopidogrel resistance. CYP2C19 is responsible, in&#xD;
      part, for converting the clopidogrel prodrug into an active metabolite that irreversibly&#xD;
      binds to the P2Y12 receptor thus inhibiting ADP-induced platelet aggregation. CYP2C19*2 and&#xD;
      *3, which encounter loss function, have been demonstrated to be the most common genetic&#xD;
      variants resulting in clopidogrel resistance.&#xD;
&#xD;
      Methods: Patients who undergo coronary stenting will be randomized to a prospective CYP2C19&#xD;
      genotype-guided antiplatelet therapy arm versus a conventional therapy arm. Venous blood&#xD;
      collection will be completed immediately after randomization in all patients eligible for the&#xD;
      study. The genotype results involving CYP2C19*2 and *3 allele variants will be obtained&#xD;
      within 48 hours only in the genotyping arm. CYP2C19 *2 or *3 reduced function allele patients&#xD;
      will receive ticagrelor 90 mg bid, whereas non-*2 or -*3 CYP2C19 patients will receive&#xD;
      clopidogrel 75 mg once daily. The conventional therapy arm will receive either clopidogrel or&#xD;
      ticagrelor, according to the clinical and procedural characteristics of patients. The dual&#xD;
      antiplatelet therapy will last for at least one year in the both arms. The primary endpoints&#xD;
      will be evaluated at one-year follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 27, 2019</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)</measure>
    <time_frame>1 year</time_frame>
    <description>MACCE will include all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI) and ischemia driven revascularization at one-year follow-up.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">4009</enrollment>
  <condition>Angina, Stable</condition>
  <condition>Acute Coronary Syndrome</condition>
  <condition>Drug-Eluting Stents</condition>
  <condition>Genotype</condition>
  <arm_group>
    <arm_group_label>Conventional Therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to the Conventional Therapy arm will receive either clopidogrel or ticagrelor, according to the clinical and procedural characteristics of patients. CYP2C19 genotyping will be performed at the end of study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CYP2C19 Genotyping</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CYP2C19 genotyping will be performed within 48 hours after randomization. CYP2C19 *2 or *3 reduced function allele patients will receive ticagrelor 90 mg bid, whereas non-*2 or -*3 CYP2C19 patients will receive clopidogrel 75 mg once daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>CYP2C19 genotype testing</intervention_name>
    <description>CYP2C19 genotype testing will be conducted in a designated central laboratory.</description>
    <arm_group_label>CYP2C19 Genotyping</arm_group_label>
    <other_name>clopidogrel</other_name>
    <other_name>ticagrelor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient ≥18 years of age&#xD;
&#xD;
          -  Patient presents with acute coronary syndrome (ACS) or stable coronary artery disease&#xD;
             (SCAD)&#xD;
&#xD;
          -  Patient has a percutaneous coronary intervention (PCI) indication and the new&#xD;
             generation drug eluting stent(s) is successfully implanted&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient unable to receive 12 months of dual anti-platelet therapy&#xD;
&#xD;
          -  Patient developing procedure-related complications such as stent thrombosis, coronary&#xD;
             dissection, coronary perforation, cardiac tamponade or no-reflow during PCI&#xD;
&#xD;
          -  Contraindicated or allergic to clopidogrel or ticagrelor&#xD;
&#xD;
          -  Patient or physician refusal to enroll in the study&#xD;
&#xD;
          -  Patient having received thrombolytic therapy within the previous 24 hours&#xD;
&#xD;
          -  Physician has known the patient's CYP2C19 genotype&#xD;
&#xD;
          -  Anticipated discontinuation of dual anti-platelet therapy within the 12-month&#xD;
             follow-up period, example for elective surgery&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  Patient has a history of bleeding diathesis or coagulopathy&#xD;
&#xD;
          -  Patient has an active pathological bleeding, such as active gastrointestinal (GI)&#xD;
             bleeding&#xD;
&#xD;
          -  Patient is pregnant, breastfeeding, or planning to become pregnant within 12 months&#xD;
&#xD;
          -  Patient is receiving chronic oral anticoagulation therapy (i.e., vitamin K antagonist,&#xD;
             direct thrombin inhibitor, Factor Xa inhibitor)&#xD;
&#xD;
          -  Patient with cardiogenic shock or mechanical circulatory assist devices placed&#xD;
&#xD;
          -  Patient with LVEF &lt;30%&#xD;
&#xD;
          -  Patient with active liver diseases&#xD;
&#xD;
          -  Patient with severe renal insufficiency (eGFR &lt;30ml/min/1.73m2 based on simplified&#xD;
             MDRD equation or CrCl &lt;30ml/min based on Cockcroft-Gault equation)&#xD;
&#xD;
          -  Patient has a malignancy or a life expectancy of less than one year&#xD;
&#xD;
          -  Platelet count &lt;100 000/μL, or hematocrit &lt;32% or &gt;52%, or white blood cell count&#xD;
             &lt;3000/μL&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yujie Zhou, PhD,MD</last_name>
    <role>Study Chair</role>
    <affiliation>Beijing Anzhen Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yujie Zhou, PhD,MD</last_name>
    <phone>8613901330652</phone>
    <email>azzyj12@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Chaoyang Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xinchun Yang, PhD, MD</last_name>
      <phone>8613651305801</phone>
      <email>YXC6229@sina.com</email>
    </contact>
    <investigator>
      <last_name>Xinchun Yang, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing Anzhen Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yujie Zhou, PhD, MD</last_name>
      <phone>8613901330652</phone>
      <email>azzyj12@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Xiaoteng Ma, MD</last_name>
      <phone>8618810616459</phone>
      <email>maxiaotengai@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yujie Zhou, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xiaoli Liu, PhD, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhujun Shen, PhD, MD</last_name>
      <phone>8613801199495</phone>
      <email>zhujun66shen@126.com</email>
    </contact>
    <investigator>
      <last_name>Zhujun Shen, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fuwai Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100037</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yanmin Yang, PhD, MD</last_name>
      <phone>8613501241275</phone>
      <email>yymfuwai@163.com</email>
    </contact>
    <investigator>
      <last_name>Yanmin Yang, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing Friendship Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100050</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hui Chen, PhD, MD</last_name>
      <phone>8613910710028</phone>
      <email>chenhui72@aliyun.com</email>
    </contact>
    <investigator>
      <last_name>Hui Chen, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing Tian Tan Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100070</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Beijing Tong Ren Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xubo Shi, PhD, MD</last_name>
      <phone>8613601217923</phone>
      <email>shixubo@vip.sina.com</email>
    </contact>
    <investigator>
      <last_name>Xubo Shi, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing LuHe Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>101199</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jincheng Guo, PhD, MD</last_name>
      <phone>8613521968844</phone>
      <email>guojcmd@126.com</email>
    </contact>
    <investigator>
      <last_name>Jincheng Guo, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing Tsinghua Changgung Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>102218</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ping Zhang, PhD, MD</last_name>
      <phone>8615712917258</phone>
      <email>zhpdoc@126.com</email>
    </contact>
    <investigator>
      <last_name>Ping Zhang, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>China-Japan Friendship Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jingang Zheng, PhD, MD</last_name>
      <phone>8613810862755</phone>
      <email>jingangzheng@yahoo.com</email>
    </contact>
    <investigator>
      <last_name>Jingang Zheng, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Affiliated Hospital of Xuzhou Medical University</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <zip>221002</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yuan Lu, PhD, MD</last_name>
      <phone>8613952110901</phone>
      <email>luyuan329@163.com</email>
    </contact>
    <investigator>
      <last_name>Yuan Lu, PhD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West China Hospital Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>November 4, 2021</last_update_submitted>
  <last_update_submitted_qc>November 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Anzhen Hospital</investigator_affiliation>
    <investigator_full_name>Yujie Zhou</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Angina, Stable</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03783351
org study id: GUARANTEE
nct id: NCT03783351
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to assess the efficacy and safety of the CYP2C19 genotype guided
      antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19*2 or *3
      allele and ticagrelor in carriers of a CYP2C19*2 or *3 allele in patients treated with new
      generation drug eluting stents.
Background: P2Y12 receptor inhibitors are crucial for the management of patients undergoing
      coronary stenting. Although large-scale trials have shown that ticagrelor is superior to
      clopidogrel in terms of platelet inhibition and reduction of major adverse cardiovascular
      events (MACE), clopidogrel remains the most commonly used P2Y12 receptor inhibitor due to its
      lower price and bleeding risk. Despite the combined use of aspirin and clopidogrel, a
      substantial portion of patients after coronary stenting are at increased risk for adverse
      cardiovascular events including death, myocardial infarction, and stent thrombosis. This
      phenomenon may be due to the so-called clopidogrel resistance. Cytochrome P450 2C19 (CYP2C19)
      polymorphism plays a crucial role in the clopidogrel resistance. CYP2C19 is responsible, in
      part, for converting the clopidogrel prodrug into an active metabolite that irreversibly
      binds to the P2Y12 receptor thus inhibiting ADP-induced platelet aggregation. CYP2C19*2 and
      *3, which encounter loss function, have been demonstrated to be the most common genetic
      variants resulting in clopidogrel resistance.

      Methods: Patients who undergo coronary stenting will be randomized to a prospective CYP2C19
      genotype-guided antiplatelet therapy arm versus a conventional therapy arm. Venous blood
      collection will be completed immediately after randomization in all patients eligible for the
      study. The genotype results involving CYP2C19*2 and *3 allele variants will be obtained
      within 48 hours only in the genotyping arm. CYP2C19 *2 or *3 reduced function allele patients
      will receive ticagrelor 90 mg bid, whereas non-*2 or -*3 CYP2C19 patients will receive
      clopidogrel 75 mg once daily. The conventional therapy arm will receive either clopidogrel or
      ticagrelor, according to the clinical and procedural characteristics of patients. The dual
      antiplatelet therapy will last for at least one year in the both arms. The primary endpoints
      will be evaluated at one-year follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)
time frame: 1 year
description: MACCE will include all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI) and ischemia driven revascularization at one-year follow-up.
arm group label: Conventional Therapy
arm group type: No Intervention
description: Patients randomized to the Conventional Therapy arm will receive either clopidogrel or ticagrelor, according to the clinical and procedural characteristics of patients. CYP2C19 genotyping will be performed at the end of study.
arm group label: CYP2C19 Genotyping
arm group type: Active Comparator
description: CYP2C19 genotyping will be performed within 48 hours after randomization. CYP2C19 *2 or *3 reduced function allele patients will receive ticagrelor 90 mg bid, whereas non-*2 or -*3 CYP2C19 patients will receive clopidogrel 75 mg once daily.
intervention type: Genetic
intervention name: CYP2C19 genotype testing
description: CYP2C19 genotype testing will be conducted in a designated central laboratory.
arm group label: CYP2C19 Genotyping
other name: clopidogrel
other name: ticagrelor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yujie Zhou, PhD,MD
role: Study Chair
affiliation: Beijing Anzhen Hospital
last name: Yujie Zhou, PhD,MD
phone: 8613901330652
email: azzyj12@163.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Anzhen Hospital
investigator full name: Yujie Zhou
investigator title: Professor
mesh term: Acute Coronary Syndrome
mesh term: Angina, Stable
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: No