<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/NCT02975076</url>
  </required_header>
  <id_info>
    <org_study_id>XH-16-037</org_study_id>
    <nct_id>NCT02975076</nct_id>
  </id_info>
  <brief_title>Sanchitongtshu Plus Asprine for Minor Ischemic Stroke or Transient Ischemic Attack: A Randomized Double-blind Study</brief_title>
  <official_title>Radix/Rhizoma Notoginseng Extract (Sanchitongtshu) Plus Asprine for Minor Ischemic Stroke or Transient Ischemic Attack: A Randomized Double-blind Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Agents of sanchi have been widely used as a complementary medicine for stroke in China.&#xD;
      Sanchitongshu is a new Chinese patent medicine extracted from sanchi which has stronger&#xD;
      anti-platelet activity than other agents of sanchi. The investigators's aim was to&#xD;
      investigate the synergistic action of aspirin combined with sanchitongshu capsule in the&#xD;
      treatment of patients with minor ischemic stroke and transient ischemic attack.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transient ischemic attack (TIA) and acute minor ischemic stroke are common and often lead to&#xD;
      disabling events. In China, there are approximately 3 million new strokes every year, and&#xD;
      approximately 30% of them are minor ischemic strokes. The incidence of TIA in China has not&#xD;
      been determined, but on the basis of the incidence in other countries, there are probably&#xD;
      more than 2 million TIAs annually in China. The risk of another stroke occurring after a TIA&#xD;
      or minor stroke is high, with approximately 10 to 20% of patients having a stroke within 3&#xD;
      months after the index event; most of these strokes occur within the first 2 days. The role&#xD;
      of antiplatelet therapy for secondary stroke prevention has been well established.&#xD;
&#xD;
      As yet, aspirin is the only antiplatelet agent that has been studied in the acute phase of&#xD;
      stroke, during which its benefit is modest. Clopidogrel in High-Risk Patients with Acute&#xD;
      Nondisabling Cerebrovascular Events (CHANCE) trial shows that among patients with high-risk&#xD;
      TIA or minor ischemic stroke who are initially seen within 24 hours after symptom onset,&#xD;
      treatment with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone for a&#xD;
      total of 90 days, is superior to aspirin alone in reducing the risk of subsequent stroke&#xD;
      events. The combination of clopidogrel with aspirin did not cause more hemorrhagic events in&#xD;
      this patient population than aspirin alone. The analytical results provided basis for the&#xD;
      synergistical effect of Aspirin and clopidogrel in inhibiting platelet aggregation. However,&#xD;
      long term use of clopidogrel bring people financial burden so that the patients have less&#xD;
      compliance of medication. Therefore, the investigators need to explore new treatment for more&#xD;
      effective, safe and economic.&#xD;
&#xD;
      Sanchi is one of the most widely used herbal medicine in China for ischemic stroke, of which&#xD;
      panax notoginseng saponins (PNS) are the main active components. Previously there were lots&#xD;
      of clinical trials on agents of PNS for ischemic stroke in China and had positive results.&#xD;
      Sanchitongshu capsule is a new Chinese patent medicine extracted from sanchi. 80% of the&#xD;
      ingredients in sanchi-tongshu capsule are panaxatriol saponins (PTS) and 60% of PTS are Rg1&#xD;
      which has strongest anti-platelet activity of all the PNS. PTS were proven by experiment and&#xD;
      phase III clinical trials to have antithrombosis effect through mechanisms of inhibiting&#xD;
      platelet aggregation, decreasing blood viscosity, strengthening activities of fibrinolysis&#xD;
      system, and promoting vascular endothelial NO releasing. More recent experimental studies&#xD;
      indicated anti-inflammatory and neuroprotective effect of PTS. Compared with other agents of&#xD;
      Sanchi, Sanchitongshu capsule contains higher purity of PTS and Rg1. Thus, Sanchitongshu&#xD;
      capsule theoretically should be vigorous in improving ischemic status after ischemic stroke.&#xD;
&#xD;
      Include, the investigators will investigate the synergistic action of aspirin combined with&#xD;
      sanchitongshu capsule in the treatment of patients with minor ischemic stroke and transient&#xD;
      ischemic attack.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Anticipated">November 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients with the180-day new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage)</measure>
    <time_frame>180 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with the 180-day new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as a cluster and evaluated individually</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 180 days follow-up</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 180 days follow-up)</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Further efficacy exploratory analysis:Impairment (changes in Barthel Index at 180 days follow-up)</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Further efficacy exploratory analysis: stroke impact scale</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy endpoint will also be analyzed stratified by etiological subtypes</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>death from any cause</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 180 days</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Intracranial hemorrhage events at 180 days</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Stroke, Acute</condition>
  <condition>Ischemic Attack, Transient</condition>
  <arm_group>
    <arm_group_label>Sanchitongshu &amp; placebo of lopidogrel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>sanchitongshu 1 capsule each time ,three times a day and Aspirin 75mg for 90 days ; placebo of clopidogrel 75mg daily for 21 days after randomization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo of Sanchitongshu &amp; lopidogrel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo of sanchitongshu1 capsule each time ,three times a day and Aspirin 75mg for 90 days;clopidogrel 75mg per day for 21 days after randomization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sanchitongshu</intervention_name>
    <description>The study drugs were manufactured according to Good Manufacturing Practice (GMP) by the Pharmaceutical Factory of Chengdu Huasun Group Inc. Ltd. and presented in the form capsules. Every Sanchitongshu capsule weighed 200 mg, contained 100 mg of panaxatriol saponin (PTS) and 100 mg inactive excipient (starch). PTS comprised of dried extracts from roots of Radix Notoginseng, and had been standardised with respect to Ginsenoside Rg1 (50%), Ginsenoside Re (6%), Notoginsenoside R1 (11%). The amounts of the active ingredients were determined by analytical RP-HPLC using an acetonitrile-water gradient system as mobile hase. The peaks were detected by UV-DAD.</description>
    <arm_group_label>Sanchitongshu &amp; placebo of lopidogrel</arm_group_label>
    <other_name>Radix/Rhizoma Notoginseng extract</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo of Sanchitongshu</intervention_name>
    <description>The Sanchitongshu placebo capsule contained dark brown muscovado sugar and the same inactive excipient (starch).</description>
    <arm_group_label>placebo of Sanchitongshu &amp; lopidogrel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <arm_group_label>Sanchitongshu &amp; placebo of lopidogrel</arm_group_label>
    <arm_group_label>placebo of Sanchitongshu &amp; lopidogrel</arm_group_label>
    <other_name>Aspirin Enteric-coated Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <arm_group_label>placebo of Sanchitongshu &amp; lopidogrel</arm_group_label>
    <other_name>Clopidogrel Bisulfate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo of clopidogrel</intervention_name>
    <arm_group_label>Sanchitongshu &amp; placebo of lopidogrel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age of 40 years to 80 years&#xD;
&#xD;
          2. diagnosis of an acute minor ischemic stroke or transient ischemic attack; and ability&#xD;
             to start the study drug within 24 hours after symptom onset, which was defined as the&#xD;
             point at which the patient reported no longer being in a normal condition. Acute minor&#xD;
             stroke was defined by a score of 3 or less at the time of randomization on the&#xD;
             National Institutes of Health Stroke Scale(NIHSS). TIA was defined as focal brain&#xD;
             ischemia with resolution of symptoms within 24 hours after onset plus a&#xD;
             moderate-to-high risk of stroke recurrence(defined as a score≥4 at the time of&#xD;
             randomization on the ABCD2). All patients were confirmed by brain CT or MRI.&#xD;
&#xD;
          3. Patients had ability to accept the medicine and rules of the research.&#xD;
&#xD;
          4. Patients had no serious complications and had normal renal function and liver&#xD;
             function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. age younger than 40 and older than 80&#xD;
&#xD;
          2. Patients need thrombolysis&#xD;
&#xD;
          3. hemorrhage; other conditions, such as vascular malformation, tumor, abcess, or other&#xD;
             major nonischemic brain disease&#xD;
&#xD;
          4. isolated sensory symptoms(e.g., numbness), isolated visual changes, or isolated&#xD;
             dizziness or vertigo without evidence of acute infarction on baseline CT or MRI of the&#xD;
             head&#xD;
&#xD;
          5. a score of more than 2 on the modified Rankin scale(scores ranges from 0(no symptoms)&#xD;
             to 6(death))immediately before the occurrence of the index ischemic stroke or TIA,&#xD;
             indicating moderate disability or worse at baseline&#xD;
&#xD;
          6. TIA or minor stroke caused by angiography or surgery&#xD;
&#xD;
          7. a clear indication for anticoagulation therapy(presumed cardiac source of embolus,&#xD;
             such as atrial fibrillation or prosthetic cardio valve)&#xD;
&#xD;
          8. anticipated requirement for long-term nonstudy antiplatelet drugs or for non steroidal&#xD;
             antiinflammatory drugs affecting platelet function&#xD;
&#xD;
          9. accompanied with severe disorders of heart, liver, and kidney&#xD;
&#xD;
         10. severe noncardiovascular coexisting condition, with a life expectancy of less than 3&#xD;
             months.&#xD;
&#xD;
         11. history of hemorrhage or bleeding tendency of other system( such as thrombocytopenic&#xD;
             purpura)&#xD;
&#xD;
         12. gastrointestinal bleeding or major surgery within the previous 3 months&#xD;
&#xD;
         13. planned or probable revascularization(any angioplasty or vascular surgery)within 3&#xD;
             months after.Operation or Interventional Therapy require discontinuation of study drug&#xD;
&#xD;
         14. Aspirin, clopidogrel or notoginseng allergy&#xD;
&#xD;
         15. a history of alcoholism or drug abuse in past 12 months&#xD;
&#xD;
         16. pregnant and lactating women, or women of childbearing age without taking any&#xD;
             effective contraceptive measures&#xD;
&#xD;
         17. patients have other serious disease or abnormal laboratory results that is unfavorable&#xD;
             to join the research&#xD;
&#xD;
         18. patients receiving other investigational drugs or devices&#xD;
&#xD;
         19. incomprehension of the character and category of the research and unable to follow the&#xD;
             research plan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xinhua Hospital</last_name>
    <role>Study Director</role>
    <affiliation>Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiaorong Wang, Master</last_name>
    <phone>13621712767</phone>
    <email>wangxr_mail@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Fei Lu</last_name>
    <phone>021-25076146</phone>
    <email>xinhuakeyan@163.com</email>
  </overall_contact_backup>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>November 22, 2016</last_update_submitted>
  <last_update_submitted_qc>November 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sanchitongshu</keyword>
  <keyword>Acute Minor Stroke</keyword>
  <keyword>Transient Ischemic Attack</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>
    <mesh_term>Ischemic Attack, Transient</mesh_term>
    <mesh_term>Ischemia</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>Yes</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/NCT02975076
org study id: XH-16-037
nct id: NCT02975076
lead sponsor: 
has dmc: No
Agents of sanchi have been widely used as a complementary medicine for stroke in China.
      Sanchitongshu is a new Chinese patent medicine extracted from sanchi which has stronger
      anti-platelet activity than other agents of sanchi. The investigators's aim was to
      investigate the synergistic action of aspirin combined with sanchitongshu capsule in the
      treatment of patients with minor ischemic stroke and transient ischemic attack.
Transient ischemic attack (TIA) and acute minor ischemic stroke are common and often lead to
      disabling events. In China, there are approximately 3 million new strokes every year, and
      approximately 30% of them are minor ischemic strokes. The incidence of TIA in China has not
      been determined, but on the basis of the incidence in other countries, there are probably
      more than 2 million TIAs annually in China. The risk of another stroke occurring after a TIA
      or minor stroke is high, with approximately 10 to 20% of patients having a stroke within 3
      months after the index event; most of these strokes occur within the first 2 days. The role
      of antiplatelet therapy for secondary stroke prevention has been well established.

      As yet, aspirin is the only antiplatelet agent that has been studied in the acute phase of
      stroke, during which its benefit is modest. Clopidogrel in High-Risk Patients with Acute
      Nondisabling Cerebrovascular Events (CHANCE) trial shows that among patients with high-risk
      TIA or minor ischemic stroke who are initially seen within 24 hours after symptom onset,
      treatment with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone for a
      total of 90 days, is superior to aspirin alone in reducing the risk of subsequent stroke
      events. The combination of clopidogrel with aspirin did not cause more hemorrhagic events in
      this patient population than aspirin alone. The analytical results provided basis for the
      synergistical effect of Aspirin and clopidogrel in inhibiting platelet aggregation. However,
      long term use of clopidogrel bring people financial burden so that the patients have less
      compliance of medication. Therefore, the investigators need to explore new treatment for more
      effective, safe and economic.

      Sanchi is one of the most widely used herbal medicine in China for ischemic stroke, of which
      panax notoginseng saponins (PNS) are the main active components. Previously there were lots
      of clinical trials on agents of PNS for ischemic stroke in China and had positive results.
      Sanchitongshu capsule is a new Chinese patent medicine extracted from sanchi. 80% of the
      ingredients in sanchi-tongshu capsule are panaxatriol saponins (PTS) and 60% of PTS are Rg1
      which has strongest anti-platelet activity of all the PNS. PTS were proven by experiment and
      phase III clinical trials to have antithrombosis effect through mechanisms of inhibiting
      platelet aggregation, decreasing blood viscosity, strengthening activities of fibrinolysis
      system, and promoting vascular endothelial NO releasing. More recent experimental studies
      indicated anti-inflammatory and neuroprotective effect of PTS. Compared with other agents of
      Sanchi, Sanchitongshu capsule contains higher purity of PTS and Rg1. Thus, Sanchitongshu
      capsule theoretically should be vigorous in improving ischemic status after ischemic stroke.

      Include, the investigators will investigate the synergistic action of aspirin combined with
      sanchitongshu capsule in the treatment of patients with minor ischemic stroke and transient
      ischemic attack.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Investigator, Outcomes Assessor)
measure: Percentage of patients with the180-day new vascular events, defined as any event of the following: Any stroke (ischemic or hemorrhage)
time frame: 180 days
measure: Percentage of patients with the 180-day new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as a cluster and evaluated individually
time frame: 180 days
measure: Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 180 days follow-up
time frame: 180 days
measure: Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 180 days follow-up)
time frame: 180 days
measure: Further efficacy exploratory analysis:Impairment (changes in Barthel Index at 180 days follow-up)
time frame: 180 days
measure: Further efficacy exploratory analysis: stroke impact scale
time frame: 180 days
measure: Efficacy endpoint will also be analyzed stratified by etiological subtypes
time frame: 180 days
measure: death from any cause
time frame: 180 days
measure: Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.
time frame: 180 days
measure: Incidence symptomatic and asymptomatic intracranial hemorrhagic events at 180 days
time frame: 180 days
measure: Incidence Intracranial hemorrhage events at 180 days
time frame: 180 days
arm group label: Sanchitongshu & placebo of lopidogrel
arm group type: Experimental
description: sanchitongshu 1 capsule each time ,three times a day and Aspirin 75mg for 90 days ; placebo of clopidogrel 75mg daily for 21 days after randomization
arm group label: placebo of Sanchitongshu & lopidogrel
arm group type: Placebo Comparator
description: placebo of sanchitongshu1 capsule each time ,three times a day and Aspirin 75mg for 90 days;clopidogrel 75mg per day for 21 days after randomization
intervention type: Drug
intervention name: Sanchitongshu
description: The study drugs were manufactured according to Good Manufacturing Practice (GMP) by the Pharmaceutical Factory of Chengdu Huasun Group Inc. Ltd. and presented in the form capsules. Every Sanchitongshu capsule weighed 200 mg, contained 100 mg of panaxatriol saponin (PTS) and 100 mg inactive excipient (starch). PTS comprised of dried extracts from roots of Radix Notoginseng, and had been standardised with respect to Ginsenoside Rg1 (50%), Ginsenoside Re (6%), Notoginsenoside R1 (11%). The amounts of the active ingredients were determined by analytical RP-HPLC using an acetonitrile-water gradient system as mobile hase. The peaks were detected by UV-DAD.
arm group label: Sanchitongshu & placebo of lopidogrel
other name: Radix/Rhizoma Notoginseng extract
intervention type: Drug
intervention name: placebo of Sanchitongshu
description: The Sanchitongshu placebo capsule contained dark brown muscovado sugar and the same inactive excipient (starch).
arm group label: placebo of Sanchitongshu & lopidogrel
intervention type: Drug
intervention name: Aspirin
arm group label: Sanchitongshu & placebo of lopidogrel
arm group label: placebo of Sanchitongshu & lopidogrel
other name: Aspirin Enteric-coated Tablets
intervention type: Drug
intervention name: Clopidogrel
arm group label: placebo of Sanchitongshu & lopidogrel
other name: Clopidogrel Bisulfate
intervention type: Drug
intervention name: placebo of clopidogrel
arm group label: Sanchitongshu & placebo of lopidogrel
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Xinhua Hospital
role: Study Director
affiliation: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
last name: Xiaorong Wang, Master
phone: 13621712767
email: wangxr_mail@163.com
last name: Fei Lu
phone: 021-25076146
email: xinhuakeyan@163.com
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemic Attack, Transient
mesh term: Ischemia
mesh term: Aspirin
mesh term: Clopidogrel
sharing ipd: Yes