<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/NCT04420351</url>
  </required_header>
  <id_info>
    <org_study_id>2017YFC1308202</org_study_id>
    <nct_id>NCT04420351</nct_id>
  </id_info>
  <brief_title>Thrombolysis of Urokinase for Minor Stroke</brief_title>
  <acronym>TRUST</acronym>
  <official_title>A Phase ⅢB, Prospective, Randomized, Open Label, Blinded-endpoint, Multicenter Trial of the Efficacy and Safety of Urokinase Thrombolysis Comparing With Antiplatelet Agents for Patients With Minor Stroke.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Tiantan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai 10th People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>General Hospital of Shenyang Military Region</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The First Affiliated Hospital of Zhengzhou 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>
      This trial will enroll patients that have been diagnosed with minor stroke, which has&#xD;
      occurred within the past 6 hours. TRUST is a prospective multicenter, randomized,&#xD;
      blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for&#xD;
      patients with minor stroke.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      China is currently faced with the heaviest stroke burden due to the tremendous population and&#xD;
      susceptibility to cerebrovascular disease. As has been assessed, deaths caused by&#xD;
      cerebrovascular disease are three times of cardiovascular disease. Within whole population&#xD;
      with cerebrovascular disease, minor stoke have taken a significant part of the disease&#xD;
      burden. Thus the population with minor stoke is one of the most important parts in efficient&#xD;
      prevention of cerebrovascular disease. According to phase I and II data from national stoke&#xD;
      registration in China, 35.25% to 42.23% cases were minor ischemic strokes. However, in&#xD;
      clinical practice, the minor ischemic stroke patients are likely to be ignored and some might&#xD;
      have poor prognosis. As has been demonstrated by a number of studies, up to one third of the&#xD;
      acute non-disabling ischemic stroke without in-time thrombolysis may suffer from disabling or&#xD;
      death at 90-day follow-up.&#xD;
&#xD;
      Several studies have demonstrated the potential benefits of thrombolysis compared usually&#xD;
      with placebo, including the Third International Stroke Trail ( IST-3, rt-PA to placebo,&#xD;
      patients within 3 hours after attack, with blood pressure lower than 185/110mmHg and&#xD;
      NIHSS≤5)，National Institute of Neurological Disorders and Stroke rt-PA Stroke Study（ NINDS,&#xD;
      rt-PA to placebo, patients with mild ischemic stroke recognized by 5 different definitions）.&#xD;
&#xD;
      Urokinase is a kind of non-selective plasminogen activator, urokinase acted as effective&#xD;
      catalyzer in the transferring of both free and protein-binding plasminogen to plasmin, thus&#xD;
      inducing thrombolysis. As one of the widely used medication for intravenous thrombolysis in&#xD;
      China, urokinase has been suggested the the efficacy and safety for ischemic stroke. With&#xD;
      easier availability and lower price, urokinase has provided a promising alternation to&#xD;
      patients who need thrombolysis in China, especially in less developed areas. The Chinese&#xD;
      guideline for diagnosis and treatment of acute ischemic stroke 2018 has recommended urokinase&#xD;
      as an alternation in the treatment of acute ischemic stroke within 6-hour time window as&#xD;
      well, if rt-PA is not available or affordable. However, randomized and multicenter clinical&#xD;
      trial of urokinase thrombolysis for minor stroke is still vacant, which couldn't provide more&#xD;
      persuasive evidence.&#xD;
&#xD;
      TRUST is a prospective multicenter, randomized, single-blind evaluation study to evaluate the&#xD;
      efficacy and safety of Urokinase Thrombolysis for patients with minor stroke. The trail will&#xD;
      enroll a total of 1002 minor stroke patients within a 6 hour time window with a NIHSS score&#xD;
      ≤5 at the time of randomization. Randomization will be 1:1 to Urokinase Thrombolysis&#xD;
      (experimental) or Antiplatelet agents (control). Patients will receive 1 million units&#xD;
      urokinase dissolved by 100ml saline through intravenous infusion within 30min or oral&#xD;
      antiplatelet agents. All patients will undergo CT or MRI before treatment and will undergo&#xD;
      the second CT within 36 hours after treatment. Patients will be followed up at 36h, 7d and 90&#xD;
      days. The primary outcome measures including the proportion of patients with a modified&#xD;
      Rankin Scale(mRS) of 0 or 1 at 90-day follow-up and the patients with symptomatic&#xD;
      intracranial hemorrhage within 36 hours. Secondary outcome measures cover new vascular&#xD;
      events, the Progress of MRS score, Neurological impairment, Daily function evaluations,&#xD;
      Quality of life assessments, Overall mortality and Adverse events and severe adverse events&#xD;
      within 90 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 10, 2020</start_date>
  <completion_date type="Anticipated">December 18, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 18, 2021</primary_completion_date>
  <phase>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>Proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up</measure>
    <time_frame>90 Days</time_frame>
    <description>mRS has 0-6 points, the higher the worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of patients with symptomatic intracranial hemorrhage within 36 hours</measure>
    <time_frame>36 hours</time_frame>
    <description>Symptomatic intracranial haemorrhage within 36 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with new vascular events</measure>
    <time_frame>90 days</time_frame>
    <description>Proportion of patients with new vascular events within 90 days(Ischemic stroke / hemorrhagic stroke / TIA / myocardial infarction / vascular death)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRS score</measure>
    <time_frame>90 days</time_frame>
    <description>To evaluate the progress of MRS score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The ratio of patients with MRS 0-1 during the last visit in two groups</measure>
    <time_frame>90 days</time_frame>
    <description>mRS has 0-6 points, the higher the worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in National Institutes of Health Stroke Scale(NIHSS) score</measure>
    <time_frame>90 days</time_frame>
    <description>Neurological impairment in two groups (changes in NIHSS score at 90-day follow-up). NIHSS has 0-42 points, the higher the worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barthel index (BI) score</measure>
    <time_frame>90 days</time_frame>
    <description>Daily function evaluations(BI score at 90 days). BI has 0-100 points,the higher the bettter outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessments</measure>
    <time_frame>90 days</time_frame>
    <description>EuroQol five dimensional questionnaire (EQ-5D scale).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Overall mortality within 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events and severe adverse events</measure>
    <time_frame>90 days</time_frame>
    <description>Adverse events and severe adverse events in two groups during 90 days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1002</enrollment>
  <condition>Minor Stroke</condition>
  <arm_group>
    <arm_group_label>Urokinase thrombolysis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antiplatelet treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Urokinase thrombolysis</intervention_name>
    <description>The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.</description>
    <arm_group_label>Urokinase thrombolysis</arm_group_label>
    <other_name>Urokinase</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin;Clopidogrel</intervention_name>
    <description>The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018.</description>
    <arm_group_label>Antiplatelet treatment</arm_group_label>
    <other_name>Antiplatelet treatment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients: 18-80 years old&#xD;
&#xD;
          2. The time from last seen well to treatment &lt; 6 hours&#xD;
&#xD;
          3. Minor stroke defined as a baseline NIHSS ≤5 at the time of randomization..&#xD;
&#xD;
          4. First onset or pre-stroke mRS≤1&#xD;
&#xD;
          5. Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1.Hyperdensity on CT suggesting intracranial hemorrhage&#xD;
&#xD;
        2.Large acute stroke &gt;1/3 middle cerebral artery (MCA) territory visible on CT or MRI&#xD;
&#xD;
        3.Other contraindications of intravenous thrombolysis, including but not limited to:&#xD;
&#xD;
          1. Intracranial tumor, arteriovenous malformation&#xD;
&#xD;
          2. Coma or confirmed as severe stroke by clinical assessment (e.g. NIHSS ≥25) or proper&#xD;
             imaging methods&#xD;
&#xD;
          3. With seizure&#xD;
&#xD;
          4. Stroke attack within past three months&#xD;
&#xD;
          5. Heparin administration within 48h before onset, with APTT longer than upper limit&#xD;
&#xD;
          6. Stroke history with diabetes&#xD;
&#xD;
          7. Platelet count ≤100×10^9/L&#xD;
&#xD;
          8. Difficult to control hypertension, defined by systolic pressure ≥185mmHg or diastolic&#xD;
             pressure ≥110 mmHg in 3 tests with at least ten minutes interval, under well guided&#xD;
             medications.&#xD;
&#xD;
          9. Blood glucose &lt;50mg/dl（2.7mmol/l）or &gt;400mg/dl（22.2mmol/l）&#xD;
&#xD;
         10. Obvious hemorrhage within past 6 months&#xD;
&#xD;
         11. Oral anti-coagulation drug administration (e.g. warfarin) with INR&gt;1.5&#xD;
&#xD;
         12. Intracranial hemorrhage or suspected intracranial hemorrhage (including subarachnoid&#xD;
             hemorrhage)&#xD;
&#xD;
         13. Pregnancy or lactation.&#xD;
&#xD;
         14. History of severe CNS damage (e.g. tumor, arterial aneurysm or CNS surgery)&#xD;
&#xD;
         15. Hemorrhagic retinopathy, e.g. diabetes (hemorrhages suggested by optic impairment) or&#xD;
             other hemorrhagic ocular lesions.&#xD;
&#xD;
         16. Bacterial endocarditis or pericarditis.&#xD;
&#xD;
         17. Prolonged or traumatic CPR (&gt;2min), puncture in nonstress vessels within past 10 days,&#xD;
             such as subclavian vein puncture.&#xD;
&#xD;
         18. Acute pancreatitis.&#xD;
&#xD;
         19. Confirmed ulcerative gastric or intestinal problems within 3 months.&#xD;
&#xD;
         20. Arterial aneurysm or arteriovenous malformation.&#xD;
&#xD;
         21. Any tumor that increase risk of hemorrhage.&#xD;
&#xD;
         22. Severe hepatic diseases, like hepatic failure, liver cirrhosis, portal hypertension,&#xD;
             esophageal varices or active hepatitis.&#xD;
&#xD;
         23. Major surgery, severe trauma or craniocerebral trauma within past 10 days.&#xD;
&#xD;
         24. Allergy to any components of urokinase.&#xD;
&#xD;
        4.Severe, fatal diseases with less than 3 month expected survival.&#xD;
&#xD;
        5.Intended to receive standard rt-PA thrombolysis or intravascular therapy.&#xD;
&#xD;
        6.Already participating in other studies that conflict to this study.&#xD;
&#xD;
        7.Unable to accomplish the follow-up.&#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>Bo Song, MD;PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital of Zhengzhou University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yongli Tao, MD;PhD</last_name>
    <phone>+86-371-66278068</phone>
    <email>tyl2112@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yafang Xu, MD</last_name>
    <phone>+86-371-66278067</phone>
    <email>yafangxu321@163.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol. 2007 May;6(5):456-64. doi: 10.1016/S1474-4422(07)70004-2.</citation>
    <PMID>17434100</PMID>
  </reference>
  <reference>
    <citation>Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J, Zeng Z, Wu Y. Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, Part i: morbidity and mortality monitoring. Circulation. 2001 Jan 23;103(3):462-8. doi: 10.1161/01.cir.103.3.462.</citation>
    <PMID>11157701</PMID>
  </reference>
  <reference>
    <citation>Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011 Dec;42(12):3651-4. doi: 10.1161/STROKEAHA.111.635755. Epub 2011 Nov 3.</citation>
    <PMID>22052510</PMID>
  </reference>
  <reference>
    <citation>Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF, Schwamm LH. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke. 2011 Nov;42(11):3110-5. doi: 10.1161/STROKEAHA.111.613208. Epub 2011 Sep 8.</citation>
    <PMID>21903949</PMID>
  </reference>
  <reference>
    <citation>Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001 Apr 24;56(8):1015-20. doi: 10.1212/wnl.56.8.1015.</citation>
    <PMID>11320171</PMID>
  </reference>
  <reference>
    <citation>Nedeltchev K, Schwegler B, Haefeli T, Brekenfeld C, Gralla J, Fischer U, Arnold M, Remonda L, Schroth G, Mattle HP. Outcome of stroke with mild or rapidly improving symptoms. Stroke. 2007 Sep;38(9):2531-5. doi: 10.1161/STROKEAHA.107.482554. Epub 2007 Aug 2.</citation>
    <PMID>17673713</PMID>
  </reference>
  <reference>
    <citation>Smith EE, Abdullah AR, Petkovska I, Rosenthal E, Koroshetz WJ, Schwamm LH. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005 Nov;36(11):2497-9. doi: 10.1161/01.STR.0000185798.78817.f3. Epub 2005 Oct 6.</citation>
    <PMID>16210552</PMID>
  </reference>
  <reference>
    <citation>Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.</citation>
    <PMID>25677596</PMID>
  </reference>
  <reference>
    <citation>Khatri P, Tayama D, Cohen G, Lindley RI, Wardlaw JM, Yeatts SD, Broderick JP, Sandercock P; PRISMS and IST-3 Collaborative Groups. Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis. Stroke. 2015 Aug;46(8):2325-7. doi: 10.1161/STROKEAHA.115.009951. Epub 2015 Jun 23.</citation>
    <PMID>26106113</PMID>
  </reference>
  <reference>
    <citation>National Institute of Neurological Disorders Stroke rt-PA Stroke Study Group. Recombinant tissue plasminogen activator for minor strokes: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005 Sep;46(3):243-52. doi: 10.1016/j.annemergmed.2005.02.013.</citation>
    <PMID>16126134</PMID>
  </reference>
  <reference>
    <citation>Khatri P, Kleindorfer DO, Yeatts SD, Saver JL, Levine SR, Lyden PD, Moomaw CJ, Palesch YY, Jauch EC, Broderick JP. Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials. Stroke. 2010 Nov;41(11):2581-6. doi: 10.1161/STROKEAHA.110.593632. Epub 2010 Sep 2.</citation>
    <PMID>20814000</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The First Affiliated Hospital of Zhengzhou University</investigator_affiliation>
    <investigator_full_name>Bo Song</investigator_full_name>
    <investigator_title>Chief of neurology department</investigator_title>
  </responsible_party>
  <keyword>Thrombolysis</keyword>
  <keyword>Urokinase</keyword>
  <keyword>Ischemic stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Clopidogrel</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/NCT04420351
org study id: 2017YFC1308202
nct id: NCT04420351
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This trial will enroll patients that have been diagnosed with minor stroke, which has
      occurred within the past 6 hours. TRUST is a prospective multicenter, randomized,
      blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for
      patients with minor stroke.
China is currently faced with the heaviest stroke burden due to the tremendous population and
      susceptibility to cerebrovascular disease. As has been assessed, deaths caused by
      cerebrovascular disease are three times of cardiovascular disease. Within whole population
      with cerebrovascular disease, minor stoke have taken a significant part of the disease
      burden. Thus the population with minor stoke is one of the most important parts in efficient
      prevention of cerebrovascular disease. According to phase I and II data from national stoke
      registration in China, 35.25% to 42.23% cases were minor ischemic strokes. However, in
      clinical practice, the minor ischemic stroke patients are likely to be ignored and some might
      have poor prognosis. As has been demonstrated by a number of studies, up to one third of the
      acute non-disabling ischemic stroke without in-time thrombolysis may suffer from disabling or
      death at 90-day follow-up.

      Several studies have demonstrated the potential benefits of thrombolysis compared usually
      with placebo, including the Third International Stroke Trail ( IST-3, rt-PA to placebo,
      patients within 3 hours after attack, with blood pressure lower than 185/110mmHg and
      NIHSS≤5)，National Institute of Neurological Disorders and Stroke rt-PA Stroke Study（ NINDS,
      rt-PA to placebo, patients with mild ischemic stroke recognized by 5 different definitions）.

      Urokinase is a kind of non-selective plasminogen activator, urokinase acted as effective
      catalyzer in the transferring of both free and protein-binding plasminogen to plasmin, thus
      inducing thrombolysis. As one of the widely used medication for intravenous thrombolysis in
      China, urokinase has been suggested the the efficacy and safety for ischemic stroke. With
      easier availability and lower price, urokinase has provided a promising alternation to
      patients who need thrombolysis in China, especially in less developed areas. The Chinese
      guideline for diagnosis and treatment of acute ischemic stroke 2018 has recommended urokinase
      as an alternation in the treatment of acute ischemic stroke within 6-hour time window as
      well, if rt-PA is not available or affordable. However, randomized and multicenter clinical
      trial of urokinase thrombolysis for minor stroke is still vacant, which couldn't provide more
      persuasive evidence.

      TRUST is a prospective multicenter, randomized, single-blind evaluation study to evaluate the
      efficacy and safety of Urokinase Thrombolysis for patients with minor stroke. The trail will
      enroll a total of 1002 minor stroke patients within a 6 hour time window with a NIHSS score
      ≤5 at the time of randomization. Randomization will be 1:1 to Urokinase Thrombolysis
      (experimental) or Antiplatelet agents (control). Patients will receive 1 million units
      urokinase dissolved by 100ml saline through intravenous infusion within 30min or oral
      antiplatelet agents. All patients will undergo CT or MRI before treatment and will undergo
      the second CT within 36 hours after treatment. Patients will be followed up at 36h, 7d and 90
      days. The primary outcome measures including the proportion of patients with a modified
      Rankin Scale(mRS) of 0 or 1 at 90-day follow-up and the patients with symptomatic
      intracranial hemorrhage within 36 hours. Secondary outcome measures cover new vascular
      events, the Progress of MRS score, Neurological impairment, Daily function evaluations,
      Quality of life assessments, Overall mortality and Adverse events and severe adverse events
      within 90 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up
time frame: 90 Days
description: mRS has 0-6 points, the higher the worse outcome.
measure: Proportion of patients with symptomatic intracranial hemorrhage within 36 hours
time frame: 36 hours
description: Symptomatic intracranial haemorrhage within 36 hours
measure: Proportion of patients with new vascular events
time frame: 90 days
description: Proportion of patients with new vascular events within 90 days(Ischemic stroke / hemorrhagic stroke / TIA / myocardial infarction / vascular death)
measure: MRS score
time frame: 90 days
description: To evaluate the progress of MRS score
measure: The ratio of patients with MRS 0-1 during the last visit in two groups
time frame: 90 days
description: mRS has 0-6 points, the higher the worse outcome.
measure: Changes in National Institutes of Health Stroke Scale(NIHSS) score
time frame: 90 days
description: Neurological impairment in two groups (changes in NIHSS score at 90-day follow-up). NIHSS has 0-42 points, the higher the worse outcome.
measure: Barthel index (BI) score
time frame: 90 days
description: Daily function evaluations(BI score at 90 days). BI has 0-100 points,the higher the bettter outcome.
measure: Quality of life assessments
time frame: 90 days
description: EuroQol five dimensional questionnaire (EQ-5D scale).
measure: Overall mortality
time frame: 90 days
description: Overall mortality within 90 days
measure: Adverse events and severe adverse events
time frame: 90 days
description: Adverse events and severe adverse events in two groups during 90 days
arm group label: Urokinase thrombolysis
arm group type: Experimental
description: The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.
arm group label: Antiplatelet treatment
arm group type: Other
description: The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018
intervention type: Drug
intervention name: Urokinase thrombolysis
description: The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.
arm group label: Urokinase thrombolysis
other name: Urokinase
intervention type: Drug
intervention name: Aspirin;Clopidogrel
description: The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018.
arm group label: Antiplatelet treatment
other name: Antiplatelet treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bo Song, MD;PhD
role: Principal Investigator
affiliation: The First Affiliated Hospital of Zhengzhou University
last name: Yongli Tao, MD;PhD
phone: +86-371-66278068
email: tyl2112@126.com
last name: Yafang Xu, MD
phone: +86-371-66278067
email: yafangxu321@163.com
citation: Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol. 2007 May;6(5):456-64. doi: 10.1016/S1474-4422(07)70004-2.
PMID: 17434100
citation: Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J, Zeng Z, Wu Y. Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, Part i: morbidity and mortality monitoring. Circulation. 2001 Jan 23;103(3):462-8. doi: 10.1161/01.cir.103.3.462.
PMID: 11157701
citation: Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011 Dec;42(12):3651-4. doi: 10.1161/STROKEAHA.111.635755. Epub 2011 Nov 3.
PMID: 22052510
citation: Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF, Schwamm LH. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke. 2011 Nov;42(11):3110-5. doi: 10.1161/STROKEAHA.111.613208. Epub 2011 Sep 8.
PMID: 21903949
citation: Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001 Apr 24;56(8):1015-20. doi: 10.1212/wnl.56.8.1015.
PMID: 11320171
citation: Nedeltchev K, Schwegler B, Haefeli T, Brekenfeld C, Gralla J, Fischer U, Arnold M, Remonda L, Schroth G, Mattle HP. Outcome of stroke with mild or rapidly improving symptoms. Stroke. 2007 Sep;38(9):2531-5. doi: 10.1161/STROKEAHA.107.482554. Epub 2007 Aug 2.
PMID: 17673713
citation: Smith EE, Abdullah AR, Petkovska I, Rosenthal E, Koroshetz WJ, Schwamm LH. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005 Nov;36(11):2497-9. doi: 10.1161/01.STR.0000185798.78817.f3. Epub 2005 Oct 6.
PMID: 16210552
citation: Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.
PMID: 25677596
citation: Khatri P, Tayama D, Cohen G, Lindley RI, Wardlaw JM, Yeatts SD, Broderick JP, Sandercock P; PRISMS and IST-3 Collaborative Groups. Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis. Stroke. 2015 Aug;46(8):2325-7. doi: 10.1161/STROKEAHA.115.009951. Epub 2015 Jun 23.
PMID: 26106113
citation: National Institute of Neurological Disorders Stroke rt-PA Stroke Study Group. Recombinant tissue plasminogen activator for minor strokes: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005 Sep;46(3):243-52. doi: 10.1016/j.annemergmed.2005.02.013.
PMID: 16126134
citation: Khatri P, Kleindorfer DO, Yeatts SD, Saver JL, Levine SR, Lyden PD, Moomaw CJ, Palesch YY, Jauch EC, Broderick JP. Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials. Stroke. 2010 Nov;41(11):2581-6. doi: 10.1161/STROKEAHA.110.593632. Epub 2010 Sep 2.
PMID: 20814000
responsible party type: Principal Investigator
investigator affiliation: The First Affiliated Hospital of Zhengzhou University
investigator full name: Bo Song
investigator title: Chief of neurology department
mesh term: Stroke
mesh term: Aspirin
mesh term: Clopidogrel
sharing ipd: No