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/NCT06037889</url>
    </required_header>
    <id_info>
      <org_study_id>BAD-RCT202201</org_study_id>
      <nct_id>NCT06037889</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Tirofiban for Patients With BAD (BRANT)</brief_title>
    <acronym>BRANT</acronym>
    <official_title>Efficacy and Safety of Tirofiban in Patients With Acute Branch Atheromatous Disease (BAD)- Related Stroke (BRANT)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Pharmaron (Chengdu) Clinical Services Co., Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Peking Union Medical College 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>
        Branch atheromatous disease (BAD)-related stroke, characterized by subcortical single&#xD;
        infarcts without severe stenosis of the large artery, but with a clear atherosclerotic&#xD;
        mechanism, is now regarded as a separate stroke type. BAD is associated with early&#xD;
        neurological deterioration and poor prognosis, but is lack of effective therapy. The goal of&#xD;
        this randomized controlled trial is to test the efficacy and safety of intravenous tirofiban&#xD;
        in patients with acute ischemic stroke caused by branch atheromatous disease. The main&#xD;
        question it aims to answer is: Compared with standard antiplatelet therapy based on current&#xD;
        stroke guideline, whether tirofiban used in acute phase of BAD could improve the proportion&#xD;
        of excellent functional outcome (modified Rankin Scale: 0-1) at 90 days. Researcher will also&#xD;
        compare the rate of major bleeding between treatment and control groups.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        BRANT study is a multicenter, randomized, open label, blinded endpoint, Parallel controlled&#xD;
        trial with the primary null hypothesis that, in patients with acute BAD-related stroke, there&#xD;
        is no difference in the proportion of excellent outcome in those treated with intravenous&#xD;
        Tirofiban compared with those treated with standard antiplatelet therapy based on guideline&#xD;
        when subjects are randomized within 48 hours of stroke onset.&#xD;
  &#xD;
        The primary objective is to determine whether intravenous tirofiban (a loading dose of&#xD;
        0.4ug/kg/min*30min followed by a maintenance dose of 0.1ug/kg/min*47.5h) is effective in&#xD;
        increasing the proportion of excellent functional outcome (mR: 0-1) at 90 days, when&#xD;
        initiated within 48 hours of onset. The active comparator is standard antiplatelet therapy&#xD;
        based on guideline [ie, 1) aspirin 150-300 mg qd, OR 2) aspirin 100 mg qd plus clopidogrel 75&#xD;
        mg qd] for 48 hours.&#xD;
  &#xD;
        Patients with acute BAD-related stroke between 18 and 75 years old, who can be randomized&#xD;
        within 48 hours of onset, and meet the BAD Diagnostic Imaging Criteria, will be enrolled. All&#xD;
        patients will conduct MRI before randomization.&#xD;
  &#xD;
        Subjects will be randomized 1:1 (Tirofiban: Standard antiplatelet therapy). The subjects'&#xD;
        eligibility will be assessed by site investigator prior to accessing the Randomization&#xD;
        Module, which is generated via the dynamic block randomization method. Only certified and&#xD;
        trained personnel can access the randomization website, who will get the information of&#xD;
        treatment (ie, Tirofiban or standard antiplatelet therapy) after the subject has be&#xD;
        determined eligible.&#xD;
  &#xD;
        The treatment period is 48 hours for both study groups. A total of 516 eligible patients will&#xD;
        be enrolled. Each participant will be followed for 90 days from randomization. The primary&#xD;
        outcome will be assessed by well-trained senior neurologists blinded to the treatment. All&#xD;
        the clinical and safety events will be re-examined by the Clinical Event Committee (CEC), who&#xD;
        are blinded during all procedures.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2025</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>
      <intervention_model_description>multi-center, randomized, open label, blinded endpoint, parallel controlled trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Our study is an open label, blinded endpoint trail. The primary outcome should be measured in a blinded manner, and the qualified evaluator is defined as: 1) Attending neurologists or above; 2) Complete the training for mRS score before the initiation of patient enrollment; 3) Blind to the antiplatelet treatment of the participants; and 4) Sign the evaluation when it is completed, and inform the other investigators of the results. All the clinical and safety events will be re-examined by the independent Clinical Event Committee (CEC), who are blinded during all procedures.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Excellent functional outcome</measure>
      <time_frame>90 days</time_frame>
      <description>Primary efficacy outcome: Excellent functional outcome is defined as modified Rankin Scale score: 0-1.&#xD;
  Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Death.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Proportion of major bleeding</measure>
      <time_frame>90 days</time_frame>
      <description>Primary safety outcome: Participants with major bleeding defined by the PLATO criteria, confirmed by the Clinical Event Committee.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Excellent functional outcome</measure>
      <time_frame>7 days</time_frame>
      <description>modified Rankin Scale score: 0-1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Early neurological deterioration</measure>
      <time_frame>7 days of randomization</time_frame>
      <description>The presence of END is determined by an increase of ≥ 4 points in the NIHSS or an increase of ≥2 points in the NIHSS motor score. In addition, NIHSS motor score refers to bilateral upper and lower extremity mobility scores. The baseline NIHSS score for the calculation of END is the first clinician-evaluated and recorded NIHSS score after onset. The time frame for post-randomization END is within 7 days of randomization.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NIHSS score</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Barthel index score</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>The Barthel Index (BI) is tool to measure the extent to which somebody can function independently and has mobility in activities of daily living (ADL), including 10 aspects: feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. Higher score indicates better performance in activities of daily living.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ischemic stroke</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>Number of participants with new-onset ischemic stroke, confirmed by senior neurologists and the Clinical Event Committee.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stroke</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>Number of participants with new-onset ischemic or hemorrhagic stroke, confirmed by senior neurologists and the Clinical Event Committee.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TIA</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>Number of participants with new-onset transient ischemic attack (TIA), confirmed by senior neurologists and the Clinical Event Committee.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite endpoint</measure>
      <time_frame>7 days and 90 days</time_frame>
      <description>Number of participants with new-onset stroke, myocardial Infarction, or all-cause death, confirmed by the Clinical Event Committee.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of Major bleeding</measure>
      <time_frame>7 days</time_frame>
      <description>Proportion of major bleeding defined by the PLATO criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serious adverse events</measure>
      <time_frame>7 and 90 days</time_frame>
      <description>Serious adverse events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>7 and 90 days</time_frame>
      <description>Adverse events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause death</measure>
      <time_frame>7 and 90 days</time_frame>
      <description>All-cause death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in hemoglobin</measure>
      <time_frame>48 hours</time_frame>
      <description>Blood test of the count of hemoglobin, g/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the count of red blood cell</measure>
      <time_frame>48 hours</time_frame>
      <description>Blood test of the count of red blood cell, 10^12/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the count of white blood cell</measure>
      <time_frame>48 hours</time_frame>
      <description>Blood test of the count of white blood cell, 10^9/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the count of platelets</measure>
      <time_frame>48 hours</time_frame>
      <description>Blood test of the count of platelets, 10^9/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in alanine transaminase</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for alanine transaminase</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in aspartate aminotransferase</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for aspartate aminotransferase</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in direct bilirubin</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for the concentration of direct bilirubin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in indirect bilirubin</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for the concentration of indirect bilirubin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in concentration of Na</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for the concentration of sodium, mmol/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the concentration of K</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for the concentration of potassium, mmol/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the concentration of creatinine</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for creatinine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the concentration of albumin</measure>
      <time_frame>48 hours</time_frame>
      <description>Serum biochemical test for albumin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the urinary occult blood</measure>
      <time_frame>48 hours</time_frame>
      <description>The test of urine blood (BLD). Negative or positive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in the fecal occult blood</measure>
      <time_frame>48 hours</time_frame>
      <description>The test of occult blood (Occult blood, OB). Negative or positive</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">516</enrollment>
    <condition>Branch Atheromatous Disease</condition>
    <arm_group>
      <arm_group_label>Tirofiban group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Intravenous tirofiban will be administered immediately after randomization for a total duration of 48h with a loading dose of 0.4ug/kg/min*30min, followed by a maintenance dose of 0.1ug/kg/min*47.5h.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard antiplatelet therapy group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Standard antiplatelet therapy based on Chinese stroke guideline will be administered after randomization for a total duration of 48h, as the two following types: 1) aspirin 150-300 mg qd, or 2) aspirin 100 mg qd plus clopidogrel 75 mg qd. The time for administration of antiplatelet drugs will be determined by the doctor in conjunction with the participants' use of antiplatelet or anticoagulant medication in the 24h prior to randomization, but the drug should be given as soon as possible after randomization.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tirofiban</intervention_name>
      <description>Tirofiban, a GPIIb/IIIa receptor inhibitor. Intravenous administration.</description>
      <arm_group_label>Tirofiban group</arm_group_label>
      <other_name>Tirofiban Hydrochloride and Sodium Chloride Injection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Aspirin tablet</intervention_name>
      <description>Aspirin. Oral administration.</description>
      <arm_group_label>Standard antiplatelet therapy group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Clopidogrel tablet</intervention_name>
      <description>Clopidogrel. Oral administration.</description>
      <arm_group_label>Standard antiplatelet therapy group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age: 18-75 years old&#xD;
  &#xD;
            2. Acute ischemic stroke&#xD;
  &#xD;
            3. Time from onset to randomization ≤48h; if onset time is unknown, time from last known&#xD;
               well to randomization ≤48h&#xD;
  &#xD;
            4. Meet the following BAD Diagnostic Imaging Criteria&#xD;
  &#xD;
               4.1. DWI infarcts: single (isolated) deep (subcortical) infarcts;&#xD;
  &#xD;
               4.2. The culprit arteries are either Lenticulostriate artery (LSA) or Paramedian&#xD;
               pontine artery (PPA), and the infarct lesion on DWI conforms to one of the following&#xD;
               characteristics (A/B): A. LSA: 1) &quot;Comma-like&quot; infarct lesions with &quot;Fan-shaped&quot;&#xD;
               extension from bottom to top in the coronary position; or 2) ≥ 3 layers (layer&#xD;
               thickness 5-7 mm) on axial DWI brain images; B. PPA: The infarct lesion extends from&#xD;
               the deep pons to the ventral pons on the axial DWI brain images;&#xD;
  &#xD;
               4.3. No more than 50% stenosis on the parent artery of the criminal artery (i.e.&#xD;
               corresponding basilar or middle cerebral artery) (Confirmed by magnetic resonance&#xD;
               angiography [MRA] or computed tomography angiography [CTA] or digital substraction&#xD;
               angiography [DSA]).&#xD;
  &#xD;
            5. Singed informed consent by the patient or legally authorized representatives.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Transient ischemic attack (TIA)&#xD;
  &#xD;
            2. Intracranial hemorrhagic diseases, vascular malformations, aneurysms, brain abscesses,&#xD;
               malignant space-occupying lesions, or other non-ischemic intracranial lesions detected&#xD;
               by baseline CT/MRI, or MRA/CTA/DSA;&#xD;
  &#xD;
            3. Presence of ≥50% stenosis in extracranial artery in tandem relationship ipsilateral to&#xD;
               the lesion;&#xD;
  &#xD;
            4. Cardiogenic embolism: atrial fibrillation, myocardial infarction, heart valve disease,&#xD;
               dilated cardiomyopathy, infective endocarditis, atrioventricular block disease, heart&#xD;
               rate less than 50 beats per minute&#xD;
  &#xD;
            5. Have received or plan to receive endovascular therapy or thrombolysis after onset;&#xD;
  &#xD;
            6. Stroke of other clear causes, e.g., moyamoya disease, arterial entrapment, vasculitis,&#xD;
               etc.&#xD;
  &#xD;
            7. modified Rankin Scale ≥2 before onset&#xD;
  &#xD;
            8. Use of tirofiban within 1 week before or after onset&#xD;
  &#xD;
            9. Low platelets (&lt;100×10^9 /L), or Prothrombin time &gt;1.3 times of the upper normal&#xD;
               limit, or INR &gt;1.5, or other systemic hemorrhagic tendencies such as hematologic&#xD;
               disorders&#xD;
  &#xD;
           10. Elevation of ALT or AST more than 1.5 times the upper normal limit;&#xD;
  &#xD;
           11. Glomerular filtration rate &lt;60 ml/min/1.73m^2&#xD;
  &#xD;
           12. Known malignant tumors&#xD;
  &#xD;
           13. History of trauma or major surgical intervention within 6 weeks prior to onset&#xD;
  &#xD;
           14. History of intracranial hemorrhage&#xD;
  &#xD;
           15. Active or recent history(within 30 days prior to onset) of clinical bleeding (e.g.,&#xD;
               gastrointestinal bleeding)&#xD;
  &#xD;
           16. Malignant hypertension (systolic blood pressure &gt;200 mmHg, or diastolic blood pressure&#xD;
               &gt;120 mmHg)&#xD;
  &#xD;
           17. Life expectancy ≤ 6 months&#xD;
  &#xD;
           18. Contraindications of 3 T MRI examination&#xD;
  &#xD;
           19. Pregnant or lactating women&#xD;
  &#xD;
           20. Have participated in another clinical trial within 3 months prior to the date of&#xD;
               informed consent, or are participating in another clinical trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jun Ni, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>The office for BRANT study</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shengde Li, MD</last_name>
      <phone>86 17896002828</phone>
      <email>lishengde.medicine@qq.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Yuhui Sha</last_name>
      <phone>86 18810678122</phone>
      <email>shayh2016@126.com</email>
    </overall_contact_backup>
    <link>
      <url>http://www.wanfangdata.com.cn/details/detail.do?_type=perio&amp;id=zgzzzz202012015</url>
      <description>Zhou LX, Ni J.Advances in Branch Atheromatous Disease. Chinese Stroke Journal 2020;15:1342- 1351</description>
    </link>
    <link>
      <url>http://www.wanfangdata.com.cn/details/detail.do?_type=perio&amp;id=zgzzzz201910013</url>
      <description>Chinese Stroke Association. Expert consensus on the clinical application of tirofiban in atherosclerotic cerebrovascular disease. Chinese Stroke Journal 2019;14:1034- 1044</description>
    </link>
    <link>
      <url>http://www.wanfangdata.com.cn/details/detail.do?_type=perio&amp;id=zhsjk201809005</url>
      <description>Chinese Society of Neurology, Cerebrovascular disease group of Chinese Society of Neurology. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. Chin J Neurol. 2018;51 9:666-82</description>
    </link>
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    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 13, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Branch atheromatous disease</keyword>
    <keyword>Tirofiban</keyword>
    <keyword>Stroke</keyword>
    <keyword>Treatment Outcome</keyword>
    <keyword>Magnetic Resonance Imaging</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Plaque, Atherosclerotic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Aspirin</mesh_term>
      <mesh_term>Tirofiban</mesh_term>
      <mesh_term>Clopidogrel</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06037889
  org study id: BAD-RCT202201
  nct id: NCT06037889
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Branch atheromatous disease (BAD)-related stroke, characterized by subcortical single
        infarcts without severe stenosis of the large artery, but with a clear atherosclerotic
        mechanism, is now regarded as a separate stroke type. BAD is associated with early
        neurological deterioration and poor prognosis, but is lack of effective therapy. The goal of
        this randomized controlled trial is to test the efficacy and safety of intravenous tirofiban
        in patients with acute ischemic stroke caused by branch atheromatous disease. The main
        question it aims to answer is: Compared with standard antiplatelet therapy based on current
        stroke guideline, whether tirofiban used in acute phase of BAD could improve the proportion
        of excellent functional outcome (modified Rankin Scale: 0-1) at 90 days. Researcher will also
        compare the rate of major bleeding between treatment and control groups.
  BRANT study is a multicenter, randomized, open label, blinded endpoint, Parallel controlled
        trial with the primary null hypothesis that, in patients with acute BAD-related stroke, there
        is no difference in the proportion of excellent outcome in those treated with intravenous
        Tirofiban compared with those treated with standard antiplatelet therapy based on guideline
        when subjects are randomized within 48 hours of stroke onset.
  
        The primary objective is to determine whether intravenous tirofiban (a loading dose of
        0.4ug/kg/min*30min followed by a maintenance dose of 0.1ug/kg/min*47.5h) is effective in
        increasing the proportion of excellent functional outcome (mR: 0-1) at 90 days, when
        initiated within 48 hours of onset. The active comparator is standard antiplatelet therapy
        based on guideline [ie, 1) aspirin 150-300 mg qd, OR 2) aspirin 100 mg qd plus clopidogrel 75
        mg qd] for 48 hours.
  
        Patients with acute BAD-related stroke between 18 and 75 years old, who can be randomized
        within 48 hours of onset, and meet the BAD Diagnostic Imaging Criteria, will be enrolled. All
        patients will conduct MRI before randomization.
  
        Subjects will be randomized 1:1 (Tirofiban: Standard antiplatelet therapy). The subjects'
        eligibility will be assessed by site investigator prior to accessing the Randomization
        Module, which is generated via the dynamic block randomization method. Only certified and
        trained personnel can access the randomization website, who will get the information of
        treatment (ie, Tirofiban or standard antiplatelet therapy) after the subject has be
        determined eligible.
  
        The treatment period is 48 hours for both study groups. A total of 516 eligible patients will
        be enrolled. Each participant will be followed for 90 days from randomization. The primary
        outcome will be assessed by well-trained senior neurologists blinded to the treatment. All
        the clinical and safety events will be re-examined by the Clinical Event Committee (CEC), who
        are blinded during all procedures.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: multi-center, randomized, open label, blinded endpoint, parallel controlled trial
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Our study is an open label, blinded endpoint trail. The primary outcome should be measured in a blinded manner, and the qualified evaluator is defined as: 1) Attending neurologists or above; 2) Complete the training for mRS score before the initiation of patient enrollment; 3) Blind to the antiplatelet treatment of the participants; and 4) Sign the evaluation when it is completed, and inform the other investigators of the results. All the clinical and safety events will be re-examined by the independent Clinical Event Committee (CEC), who are blinded during all procedures.
  measure: Excellent functional outcome
  time frame: 90 days
  description: Primary efficacy outcome: Excellent functional outcome is defined as modified Rankin Scale score: 0-1.
  Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Death.
  measure: Proportion of major bleeding
  time frame: 90 days
  description: Primary safety outcome: Participants with major bleeding defined by the PLATO criteria, confirmed by the Clinical Event Committee.
  measure: Excellent functional outcome
  time frame: 7 days
  description: modified Rankin Scale score: 0-1
  measure: Early neurological deterioration
  time frame: 7 days of randomization
  description: The presence of END is determined by an increase of ≥ 4 points in the NIHSS or an increase of ≥2 points in the NIHSS motor score. In addition, NIHSS motor score refers to bilateral upper and lower extremity mobility scores. The baseline NIHSS score for the calculation of END is the first clinician-evaluated and recorded NIHSS score after onset. The time frame for post-randomization END is within 7 days of randomization.
  measure: NIHSS score
  time frame: 7 days and 90 days
  description: The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
  measure: Barthel index score
  time frame: 7 days and 90 days
  description: The Barthel Index (BI) is tool to measure the extent to which somebody can function independently and has mobility in activities of daily living (ADL), including 10 aspects: feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. Higher score indicates better performance in activities of daily living.
  measure: Ischemic stroke
  time frame: 7 days and 90 days
  description: Number of participants with new-onset ischemic stroke, confirmed by senior neurologists and the Clinical Event Committee.
  measure: Stroke
  time frame: 7 days and 90 days
  description: Number of participants with new-onset ischemic or hemorrhagic stroke, confirmed by senior neurologists and the Clinical Event Committee.
  measure: TIA
  time frame: 7 days and 90 days
  description: Number of participants with new-onset transient ischemic attack (TIA), confirmed by senior neurologists and the Clinical Event Committee.
  measure: Composite endpoint
  time frame: 7 days and 90 days
  description: Number of participants with new-onset stroke, myocardial Infarction, or all-cause death, confirmed by the Clinical Event Committee.
  measure: Proportion of Major bleeding
  time frame: 7 days
  description: Proportion of major bleeding defined by the PLATO criteria.
  measure: Serious adverse events
  time frame: 7 and 90 days
  description: Serious adverse events
  measure: Adverse events
  time frame: 7 and 90 days
  description: Adverse events
  measure: All-cause death
  time frame: 7 and 90 days
  description: All-cause death
  measure: Changes in hemoglobin
  time frame: 48 hours
  description: Blood test of the count of hemoglobin, g/L
  measure: Changes in the count of red blood cell
  time frame: 48 hours
  description: Blood test of the count of red blood cell, 10^12/L
  measure: Changes in the count of white blood cell
  time frame: 48 hours
  description: Blood test of the count of white blood cell, 10^9/L
  measure: Changes in the count of platelets
  time frame: 48 hours
  description: Blood test of the count of platelets, 10^9/L
  measure: Changes in alanine transaminase
  time frame: 48 hours
  description: Serum biochemical test for alanine transaminase
  measure: Changes in aspartate aminotransferase
  time frame: 48 hours
  description: Serum biochemical test for aspartate aminotransferase
  measure: Changes in direct bilirubin
  time frame: 48 hours
  description: Serum biochemical test for the concentration of direct bilirubin
  measure: Changes in indirect bilirubin
  time frame: 48 hours
  description: Serum biochemical test for the concentration of indirect bilirubin
  measure: Changes in concentration of Na
  time frame: 48 hours
  description: Serum biochemical test for the concentration of sodium, mmol/L
  measure: Changes in the concentration of K
  time frame: 48 hours
  description: Serum biochemical test for the concentration of potassium, mmol/L
  measure: Changes in the concentration of creatinine
  time frame: 48 hours
  description: Serum biochemical test for creatinine
  measure: Changes in the concentration of albumin
  time frame: 48 hours
  description: Serum biochemical test for albumin
  measure: Changes in the urinary occult blood
  time frame: 48 hours
  description: The test of urine blood (BLD). Negative or positive.
  measure: Changes in the fecal occult blood
  time frame: 48 hours
  description: The test of occult blood (Occult blood, OB). Negative or positive
  arm group label: Tirofiban group
  arm group type: Experimental
  description: Intravenous tirofiban will be administered immediately after randomization for a total duration of 48h with a loading dose of 0.4ug/kg/min*30min, followed by a maintenance dose of 0.1ug/kg/min*47.5h.
  arm group label: Standard antiplatelet therapy group
  arm group type: Active Comparator
  description: Standard antiplatelet therapy based on Chinese stroke guideline will be administered after randomization for a total duration of 48h, as the two following types: 1) aspirin 150-300 mg qd, or 2) aspirin 100 mg qd plus clopidogrel 75 mg qd. The time for administration of antiplatelet drugs will be determined by the doctor in conjunction with the participants' use of antiplatelet or anticoagulant medication in the 24h prior to randomization, but the drug should be given as soon as possible after randomization.
  intervention type: Drug
  intervention name: Tirofiban
  description: Tirofiban, a GPIIb/IIIa receptor inhibitor. Intravenous administration.
  arm group label: Tirofiban group
  other name: Tirofiban Hydrochloride and Sodium Chloride Injection
  intervention type: Drug
  intervention name: Aspirin tablet
  description: Aspirin. Oral administration.
  arm group label: Standard antiplatelet therapy group
  intervention type: Drug
  intervention name: Clopidogrel tablet
  description: Clopidogrel. Oral administration.
  arm group label: Standard antiplatelet therapy group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jun Ni, MD
  role: Principal Investigator
  affiliation: The office for BRANT study
  last name: Shengde Li, MD
  phone: 86 17896002828
  email: lishengde.medicine@qq.com
  last name: Yuhui Sha
  phone: 86 18810678122
  email: shayh2016@126.com
  url: http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgzzzz202012015
  description: Zhou LX, Ni J.Advances in Branch Atheromatous Disease. Chinese Stroke Journal 2020;15:1342- 1351
  url: http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgzzzz201910013
  description: Chinese Stroke Association. Expert consensus on the clinical application of tirofiban in atherosclerotic cerebrovascular disease. Chinese Stroke Journal 2019;14:1034- 1044
  url: http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhsjk201809005
  description: Chinese Society of Neurology, Cerebrovascular disease group of Chinese Society of Neurology. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. Chin J Neurol. 2018;51 9:666-82
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  PMID: 33070714
  citation: Wu X, Liu Y, Nie C, Kang Z, Wang Q, Sun D, Li H, Liu Y, Mei B. Efficacy and Safety of Intravenous Thrombolysis on Acute Branch Atheromatous Disease: A Retrospective Case-Control Study. Front Neurol. 2020 Jul 7;11:581. doi: 10.3389/fneur.2020.00581. eCollection 2020.
  PMID: 32733357
  citation: Yi X, Zhou Q, Wang C, Lin J, Chai Z. Aspirin plus clopidogrel may reduce the risk of early neurologic deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles. J Neurol. 2018 Oct;265(10):2396-2403. doi: 10.1007/s00415-018-8998-1. Epub 2018 Aug 20.
  PMID: 30128710
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  PMID: 32345264
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  PMID: 31570084
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  PMID: 32459110
  citation: Pan X, Zheng D, Zheng Y, Chan PWL, Lin Y, Zou J, Zhou J, Yang J. Safety and efficacy of tirofiban combined with endovascular treatment in acute ischaemic stroke. Eur J Neurol. 2019 Aug;26(8):1105-1110. doi: 10.1111/ene.13946. Epub 2019 Mar 19.
  PMID: 30793464
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  PMID: 23060895
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  responsible party type: Sponsor
  mesh term: Plaque, Atherosclerotic
  mesh term: Aspirin
  mesh term: Tirofiban
  mesh term: Clopidogrel