<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/NCT04491695</url>
  </required_header>
  <id_info>
    <org_study_id>TREND</org_study_id>
    <nct_id>NCT04491695</nct_id>
  </id_info>
  <brief_title>Tirofiban for the Prevention of Neurological Deterioration in Acute Ischemic Stroke</brief_title>
  <acronym>TREND</acronym>
  <official_title>Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration of Patients With Acute Ischemic Stroke: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Capital Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Capital Medical University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, dual antiplatelet therapy with aspirin and clopidogrel (with loading doses) is&#xD;
      widely used for patients with acute ischemic stroke. However, immediate, potent and&#xD;
      reversible inhibition of platelet aggregation is not possible. Additionally, more than 5%&#xD;
      patients have aspirin resistance and more than 15% patients have clopidogrel resistance.&#xD;
      Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (Tirofiban) receptor&#xD;
      blocker with fast onset and offset of actions will provide more desired antiplatelet effects&#xD;
      in the setting of acute ischemic stroke, especially in patients with high risk of&#xD;
      neurological deterioration. This study will measure the anti-platelet effects of Tirofiban in&#xD;
      patients with acute ischemic stroke who had high risk of neurological deterioration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 12, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with a change in NIHSS by ≥ 4 points compared to enrollment NIHSS.</measure>
    <time_frame>Within 72 hours of intervention.</time_frame>
    <description>National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of the NIHSS</measure>
    <time_frame>0-30 days of intervention.</time_frame>
    <description>National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of the Scandinavian Stroke Scale</measure>
    <time_frame>0-30 days of intervention.</time_frame>
    <description>Scandinavian Stroke Scale (SSS): stroke symptom severity scale with a range of 0-58. Lower score means more severe stroke symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS).</measure>
    <time_frame>0-90 days.</time_frame>
    <description>The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of symptomatic intracerebral hemorrhage.</measure>
    <time_frame>0-90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants experienced adverse events</measure>
    <time_frame>0-90 days.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">420</enrollment>
  <condition>Acute Stroke</condition>
  <arm_group>
    <arm_group_label>Tirofiban+Oral antiplatelet therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive Tirofiban in the first 72 hours and bridge to oral antiplatelet therapy thereafter.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral antiplatelet therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive oral antiplatelet therapy alone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tirofiban Hydrochloride</intervention_name>
    <description>Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion for 71.5 hours.</description>
    <arm_group_label>Tirofiban+Oral antiplatelet therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral antiplatelet</intervention_name>
    <description>Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.</description>
    <arm_group_label>Oral antiplatelet therapy</arm_group_label>
    <arm_group_label>Tirofiban+Oral antiplatelet therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Acute ischemic stroke with 24 hours of symptom onset.&#xD;
&#xD;
          2. NIHSS≥4 and ≤20 points, and the paralyzed limbs is able to actively move the muscle&#xD;
             (standardized motor examination rating scale of 2 or much higher).&#xD;
&#xD;
          3. Age 18-80 years old.&#xD;
&#xD;
          4. Informed consent obtained from patient or acceptable patient's surrogate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treated with intravenous or endovascular thrombectomy for the indexed acute ischemic&#xD;
             stroke.&#xD;
&#xD;
          2. Acute ischemic stroke caused by determined or suspected cardioembolism.&#xD;
&#xD;
          3. Acute ischemic stroke caused by other determined caused, including moyamoya disease,&#xD;
             artery dissection, arteritis, and etc.&#xD;
&#xD;
          4. Pre-stroke mRS ≥2 or the paralyzed limbs are dyskinesia before stroke.&#xD;
&#xD;
          5. Known hematochezia, gastrointestinal bleeding and any other bleeding.&#xD;
&#xD;
          6. Allergy to tirofiban or its solvents.&#xD;
&#xD;
          7. Patients suffered from severe diseases, including malignant tumor, liver cirrhosis,&#xD;
             kidney failure, congestive heart failure, and etc.&#xD;
&#xD;
          8. Gastrointestinal or genitourinary tract bleeding within 1 years.&#xD;
&#xD;
          9. Determined coagulation disorders, platelet dysfunction, or platelet count &lt;100*109/L.&#xD;
&#xD;
         10. Major surgical operation or severe trauma within 1 month.&#xD;
&#xD;
         11. Hemorrhagic retinopathy.&#xD;
&#xD;
         12. Chronic hemodialysis.&#xD;
&#xD;
         13. Uncontrolled hypertension with systolic blood pressure &gt;180 mmHg or diastolic blood&#xD;
             pressure &gt;110 mmHg.&#xD;
&#xD;
         14. Acute pericarditis.&#xD;
&#xD;
         15. Other conditions that determined by the investigators.&#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_contact>
    <last_name>Qingfeng Ma, M.D.</last_name>
    <phone>010-83199430</phone>
    <email>m.qingfeng@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wenbo Zhao, M.D.</last_name>
    <phone>86-13120136877</phone>
    <email>zhaowb.cool@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Xuanwu Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100053</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qingfeng Ma, M.D.</last_name>
    </contact>
    <contact_backup>
      <last_name>Wenbo Zhao, M.D.</last_name>
    </contact_backup>
    <investigator>
      <last_name>Qingfeng Ma</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beijing Luhe Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Huishan Du, M.D.</last_name>
    </contact>
    <contact_backup>
      <last_name>Xiaokun Geng, M.D.</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The first Affiliated Hospital of Henan University of Science and Technology</name>
      <address>
        <city>Luoyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Junqiang Yan, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nanyang Central Hospital</name>
      <address>
        <city>Nanyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Changming Wen, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nanyang Second General Hospital</name>
      <address>
        <city>Nanyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jinhui Qin, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital of Zhengzhou University</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yuming Xu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Henan Provincial People's Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ziliang Wang, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Third People's Hospital of Hubei Province</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hunan Provincial People's Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Xiaoping Gao, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sinapharm North Hospital</name>
      <address>
        <city>Baotou</city>
        <state>Inner Mongolia Autonomous Region</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lifei Xing, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ordos Central Hospital</name>
      <address>
        <city>Ordos</city>
        <state>Inner Mongolia Autonomous Region</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaojun Hao</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tongliao City Hosptial</name>
      <address>
        <city>Tongliao</city>
        <state>Inner Mongolia Autonomous Region</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yaoming Xu, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nanjing Drum Tower Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yu Xu, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jiangxi Provincial People's Hospital</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shandong Provincial Hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Qinjian Sun, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shandong Provincial Qianfoshan Hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bo Wu, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Beichen Hospital of Traditional Chinese Medicine</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruixian Wang, M.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>TEDA Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, Zhao W, Ren M, Wu D, Ding J, Song H, Wang Y, Ma Q, Ji X. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019 Dec;50(12):3481-3487. doi: 10.1161/STROKEAHA.119.026240. Epub 2019 Oct 1.</citation>
    <PMID>31570084</PMID>
  </reference>
  <results_reference>
    <citation>Zhao W, Che R, Shang S, Wu C, Li C, Wu L, Chen J, Duan J, Song H, Zhang H, Ling F, Wang Y, Liebeskind D, Feng W, Ji X. Low-Dose Tirofiban Improves Functional Outcome in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy. Stroke. 2017 Dec;48(12):3289-3294. doi: 10.1161/STROKEAHA.117.019193. Epub 2017 Nov 10.</citation>
    <PMID>29127270</PMID>
  </results_reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>July 16, 2022</last_update_submitted>
  <last_update_submitted_qc>July 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Capital Medical University</investigator_affiliation>
    <investigator_full_name>Ji Xunming,MD,PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Acute ischemic stroke</keyword>
  <keyword>Neurological deterioration</keyword>
  <keyword>Stroke progression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tirofiban</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04491695
org study id: TREND
nct id: NCT04491695
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Currently, dual antiplatelet therapy with aspirin and clopidogrel (with loading doses) is
      widely used for patients with acute ischemic stroke. However, immediate, potent and
      reversible inhibition of platelet aggregation is not possible. Additionally, more than 5%
      patients have aspirin resistance and more than 15% patients have clopidogrel resistance.
      Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (Tirofiban) receptor
      blocker with fast onset and offset of actions will provide more desired antiplatelet effects
      in the setting of acute ischemic stroke, especially in patients with high risk of
      neurological deterioration. This study will measure the anti-platelet effects of Tirofiban in
      patients with acute ischemic stroke who had high risk of neurological deterioration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Number of patients with a change in NIHSS by ≥ 4 points compared to enrollment NIHSS.
time frame: Within 72 hours of intervention.
description: National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
measure: Change of the NIHSS
time frame: 0-30 days of intervention.
description: National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
measure: Change of the Scandinavian Stroke Scale
time frame: 0-30 days of intervention.
description: Scandinavian Stroke Scale (SSS): stroke symptom severity scale with a range of 0-58. Lower score means more severe stroke symptoms.
measure: The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS).
time frame: 0-90 days.
description: The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
measure: Rate of symptomatic intracerebral hemorrhage.
time frame: 0-90 days
measure: Number of Participants experienced adverse events
time frame: 0-90 days.
arm group label: Tirofiban+Oral antiplatelet therapy
arm group type: Experimental
description: Patients will receive Tirofiban in the first 72 hours and bridge to oral antiplatelet therapy thereafter.
arm group label: Oral antiplatelet therapy
arm group type: Active Comparator
description: Patients will receive oral antiplatelet therapy alone.
intervention type: Drug
intervention name: Tirofiban Hydrochloride
description: Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion for 71.5 hours.
arm group label: Tirofiban+Oral antiplatelet therapy
intervention type: Drug
intervention name: Oral antiplatelet
description: Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.
arm group label: Oral antiplatelet therapy
arm group label: Tirofiban+Oral antiplatelet therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Qingfeng Ma, M.D.
phone: 010-83199430
email: m.qingfeng@163.com
last name: Wenbo Zhao, M.D.
phone: 86-13120136877
email: zhaowb.cool@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
country: China
citation: Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, Zhao W, Ren M, Wu D, Ding J, Song H, Wang Y, Ma Q, Ji X. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019 Dec;50(12):3481-3487. doi: 10.1161/STROKEAHA.119.026240. Epub 2019 Oct 1.
PMID: 31570084
citation: Zhao W, Che R, Shang S, Wu C, Li C, Wu L, Chen J, Duan J, Song H, Zhang H, Ling F, Wang Y, Liebeskind D, Feng W, Ji X. Low-Dose Tirofiban Improves Functional Outcome in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy. Stroke. 2017 Dec;48(12):3289-3294. doi: 10.1161/STROKEAHA.117.019193. Epub 2017 Nov 10.
PMID: 29127270
responsible party type: Principal Investigator
investigator affiliation: Capital Medical University
investigator full name: Ji Xunming,MD,PhD
investigator title: Professor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Tirofiban