<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/NCT04475328</url>
  </required_header>
  <id_info>
    <org_study_id>PUMCH-AGNH2020</org_study_id>
    <nct_id>NCT04475328</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of AngongNiuhuang Pill in Patients With Acute Ischemic Stroke (ANGONG TRIAL)</brief_title>
  <official_title>Efficacy and Safety of AngongNiuhuang Pill in Patients With Acute Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      AngongNiuhuang pill has obvious effects on the cardiovascular and cerebrovascular diseases.&#xD;
      Pharmacological experiments confirmed that AngongNiuhuang pill can protect blood-brain&#xD;
      barrier, inhibit capillary permeability, improve the tolerance of cerebral ischemia and&#xD;
      hypoxia, reduce oxidative stress injury, thus protecting brain tissue. Clinical studies have&#xD;
      also confirmed that AngongNiuhuang pill can increase the GCS score, reduce coma, improve&#xD;
      nerve function defect and promote nerve function recovery. The primary purpose of this trial&#xD;
      was to evaluate the difference in the volume of cerebral infarction and cerebral edema&#xD;
      between Angong Niuhuang pill and placebo in patients with ischemic stroke at 14 days compared&#xD;
      with the baseline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial is a prospective, randomized, double-blinded, placebo parallel controlled,&#xD;
      multicenter trial. Patients who met the inclusion and exclusion criteria will be randomized&#xD;
      1:1 into two groups after offering informed content: 1) one group will receive AngongNiuhuang&#xD;
      pill 1pill qd/day for 5-day; 2) the other group will receive Placebo of AngongNiuhuang pill&#xD;
      1pill qd/day for 5-day. The primary purpose of this trial was to evaluate the difference in&#xD;
      the volume of cerebral infarction and cerebral edema between Angong Niuhuang pill and placebo&#xD;
      in patients with ischemic stroke at 14 days compared with the baseline. The study was&#xD;
      consisted of six visits, including the day of randomization, 2 days, 3-6 days, 7 days (the&#xD;
      endap time of the therapy), 14 days, and 90 days (the endap time of the follow-up).&#xD;
      Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment&#xD;
      neurological function rating scale will be recorded during the program. The period of the&#xD;
      trial is from August 2020 to October 2021, and 120 subjects are planned to be recruited from&#xD;
      10 centers in China. All the related investigative organizations and individuals will obey&#xD;
      the Declaration of Helsinki and Chinese Guard-cell protoplast (GCP) standard. A Data and&#xD;
      Safety Monitoring Board (DSMB) will regularly monitor safety during the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Actual">July 30, 2022</completion_date>
  <primary_completion_date type="Actual">May 1, 2022</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>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral infarction volume</measure>
    <time_frame>14 days</time_frame>
    <description>Changes in cerebral infarction volume on Day 14 of the treatment from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cerebral edema volume</measure>
    <time_frame>14 days</time_frame>
    <description>Changes in cerebral edema volume on Day 14 of the treatment from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The proportion of the patients with Severity Adverse Events within 90 days of the treatment.</measure>
    <time_frame>90 days</time_frame>
    <description>Severity Adverse Events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cerebral infarction volume</measure>
    <time_frame>90 days</time_frame>
    <description>Changes in cerebral infarction volume on Day 90 of the treatment from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cerebral edema volume</measure>
    <time_frame>90 days</time_frame>
    <description>Changes in cerebral edema volume on Day 90 of the treatment from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with Modified Rankin Scale (mRS) score ≤ 2 point on the Day 14 and 90 of treatment.</measure>
    <time_frame>14 days, 90 days</time_frame>
    <description>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 - Dead. The mRS scores between 3 to 6 points are considered to be poor functional outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in NIHSS score on Day 14 and 90 of the treatment from baseline.</measure>
    <time_frame>14 days, 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>Changes in Glasgow Coma Score (GCS) on the Day 7 and 14 of the treatment from baseline.</measure>
    <time_frame>7 days, 14 days</time_frame>
    <description>We will use the GCS score to evaluate the degree of coma. The GCS have three domain items (open-eye response, speech response, and movement). The maximum possible score is 15, with the minimum score being a 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of biomarker (hs-CRP)</measure>
    <time_frame>7 days</time_frame>
    <description>Evaluation of the change in hs-CRP on Day 7 of the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of biomarker (MMP-9)</measure>
    <time_frame>7 days</time_frame>
    <description>Evaluation of the change in MMP-9 on Day 7 of the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of biomarker (S-100B)</measure>
    <time_frame>7 days</time_frame>
    <description>Evaluation of the change in S-100B on Day 7 of the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of biomarker (NSE)</measure>
    <time_frame>7 days</time_frame>
    <description>Evaluation of the change in NSE on Day 7 of the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of the patients with Severity Adverse Events within 7 days of the treatment.</measure>
    <time_frame>7 days</time_frame>
    <description>Severity Adverse Events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in toxicology index including mercury and arsenic on Day 7 of the treatment.</measure>
    <time_frame>7 days</time_frame>
    <description>toxicology index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of the patients with Adverse Events within 7 and 90 days of the treatment.</measure>
    <time_frame>7 days, 90 days</time_frame>
    <description>Adverse Events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of the patients with All-cause mortality within 7 and 90 days of the treatment.</measure>
    <time_frame>7 days, 90 days</time_frame>
    <description>All-cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of the patients with Combined vascular events within 7 and 90 days of the treatment.</measure>
    <time_frame>7 days, 90 days</time_frame>
    <description>Combined vascular events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>AngongNiuhuang</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drugs : AngongNiuhuang pill. The other treatments will provided according to guidelines for standard treatment of acute ischemic stroke.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo of AngongNiuhuang</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drugs : Placebo of AngongNiuhuang pill. The other treatments will provided according to guidelines for standard treatment of acute ischemic stroke.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AngongNiuhuang pill</intervention_name>
    <description>This group will receive AngongNiuhuang pill 1pill qd/day for 5-day.</description>
    <arm_group_label>AngongNiuhuang</arm_group_label>
    <other_name>Angong Niuhuang Wan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo of AngongNiuhuang pill</intervention_name>
    <description>This group will receive placebo of AngongNiuhuang pill 1pill qd/day for 5-day.</description>
    <arm_group_label>Placebo of AngongNiuhuang</arm_group_label>
    <other_name>Placebo of Angong Niuhuang Wan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard treatment</intervention_name>
    <description>The other treatments according to guidelines for standard treatment of acute ischemic stroke</description>
    <arm_group_label>AngongNiuhuang</arm_group_label>
    <arm_group_label>Placebo of AngongNiuhuang</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female participates aged 40-80 years.&#xD;
&#xD;
          2. Diagnosis with acute ischemic stroke.&#xD;
&#xD;
          3. Diagnosis with acute cerebral infarctions of internal carotid artery system.&#xD;
&#xD;
          4. 10≤ Baseline NIHSS &lt;20.&#xD;
&#xD;
          5. Time of onset ≤36h.&#xD;
&#xD;
          6. Provision of informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Not suitable for taking this medicine according to the judgement of consulting&#xD;
             traditional Chinese medical doctor.&#xD;
&#xD;
          2. Suffering from intracranial tumors, encephalitis, subarachnoid hemorrhage and other&#xD;
             brain organic diseases.&#xD;
&#xD;
          3. Patients with hemorrhagic transformation after cerebral infarction.&#xD;
&#xD;
          4. Received or planned to receive endovascular treatment, including thrombectomy, ultra&#xD;
             early thrombectomy and stenting.&#xD;
&#xD;
          5. Received or planned to receive decompression craniectomy.&#xD;
&#xD;
          6. With mRS score &gt;1 before onset of this episode.&#xD;
&#xD;
          7. Participates who cannot tolerate the MRI scans, such as Using a pacemaker or automatic&#xD;
             defibrillator or having claustrophobia.&#xD;
&#xD;
          8. With thrombocytopenia (&lt;100 x10^9/L), hematologic diseases or other systemic bleeding&#xD;
             tendency.&#xD;
&#xD;
          9. With Alanine transaminase or Aspartate aminotransferase &gt;1.5 times than normal upper&#xD;
             limit or Creatinine &gt;1.5 times than normal upper limit.&#xD;
&#xD;
         10. Allergic to ingredients of AngongNiuhuang pill.&#xD;
&#xD;
         11. Received AngongNiuhuang pill within 1 month.&#xD;
&#xD;
         12. Participates who plan to become pregnant within 3 months, or women of childbearing age&#xD;
             with negative pregnancy test but refuse to accept contraception; during pregnancy or&#xD;
             lactation.&#xD;
&#xD;
         13. Participates in other clinical trials within 30 days before randomization or currently&#xD;
             involved in other clinical trails.&#xD;
&#xD;
         14. Participates with a life expectancy less than 3 months.&#xD;
&#xD;
         15. Incapable to follow this study due to mental illness, cognitive or emotional&#xD;
             disorders.&#xD;
&#xD;
         16. Participates are not eligible for this clinical trial as evaluated by the&#xD;
             investigators.&#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>Bin Peng, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hosptial, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Neurology,Peking Union Medical College Hospital,Shuaifuyuan 1,Dong Cheng District. Beijing</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Bin Peng</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Acute Ischemic Stroke</keyword>
  <keyword>AngongNiuhuang Pill</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>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_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/NCT04475328
org study id: PUMCH-AGNH2020
nct id: NCT04475328
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
AngongNiuhuang pill has obvious effects on the cardiovascular and cerebrovascular diseases.
      Pharmacological experiments confirmed that AngongNiuhuang pill can protect blood-brain
      barrier, inhibit capillary permeability, improve the tolerance of cerebral ischemia and
      hypoxia, reduce oxidative stress injury, thus protecting brain tissue. Clinical studies have
      also confirmed that AngongNiuhuang pill can increase the GCS score, reduce coma, improve
      nerve function defect and promote nerve function recovery. The primary purpose of this trial
      was to evaluate the difference in the volume of cerebral infarction and cerebral edema
      between Angong Niuhuang pill and placebo in patients with ischemic stroke at 14 days compared
      with the baseline.
This trial is a prospective, randomized, double-blinded, placebo parallel controlled,
      multicenter trial. Patients who met the inclusion and exclusion criteria will be randomized
      1:1 into two groups after offering informed content: 1) one group will receive AngongNiuhuang
      pill 1pill qd/day for 5-day; 2) the other group will receive Placebo of AngongNiuhuang pill
      1pill qd/day for 5-day. The primary purpose of this trial was to evaluate the difference in
      the volume of cerebral infarction and cerebral edema between Angong Niuhuang pill and placebo
      in patients with ischemic stroke at 14 days compared with the baseline. The study was
      consisted of six visits, including the day of randomization, 2 days, 3-6 days, 7 days (the
      endap time of the therapy), 14 days, and 90 days (the endap time of the follow-up).
      Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment
      neurological function rating scale will be recorded during the program. The period of the
      trial is from August 2020 to October 2021, and 120 subjects are planned to be recruited from
      10 centers in China. All the related investigative organizations and individuals will obey
      the Declaration of Helsinki and Chinese Guard-cell protoplast (GCP) standard. A Data and
      Safety Monitoring Board (DSMB) will regularly monitor safety during the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Cerebral infarction volume
time frame: 14 days
description: Changes in cerebral infarction volume on Day 14 of the treatment from baseline.
measure: Cerebral edema volume
time frame: 14 days
description: Changes in cerebral edema volume on Day 14 of the treatment from baseline.
measure: The proportion of the patients with Severity Adverse Events within 90 days of the treatment.
time frame: 90 days
description: Severity Adverse Events
measure: Cerebral infarction volume
time frame: 90 days
description: Changes in cerebral infarction volume on Day 90 of the treatment from baseline.
measure: Cerebral edema volume
time frame: 90 days
description: Changes in cerebral edema volume on Day 90 of the treatment from baseline.
measure: The proportion of patients with Modified Rankin Scale (mRS) score ≤ 2 point on the Day 14 and 90 of treatment.
time frame: 14 days, 90 days
description: 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 - Dead. The mRS scores between 3 to 6 points are considered to be poor functional outcome.
measure: Changes in NIHSS score on Day 14 and 90 of the treatment from baseline.
time frame: 14 days, 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: Changes in Glasgow Coma Score (GCS) on the Day 7 and 14 of the treatment from baseline.
time frame: 7 days, 14 days
description: We will use the GCS score to evaluate the degree of coma. The GCS have three domain items (open-eye response, speech response, and movement). The maximum possible score is 15, with the minimum score being a 3.
measure: Changes of biomarker (hs-CRP)
time frame: 7 days
description: Evaluation of the change in hs-CRP on Day 7 of the treatment.
measure: Changes of biomarker (MMP-9)
time frame: 7 days
description: Evaluation of the change in MMP-9 on Day 7 of the treatment.
measure: Changes of biomarker (S-100B)
time frame: 7 days
description: Evaluation of the change in S-100B on Day 7 of the treatment.
measure: Changes of biomarker (NSE)
time frame: 7 days
description: Evaluation of the change in NSE on Day 7 of the treatment.
measure: The proportion of the patients with Severity Adverse Events within 7 days of the treatment.
time frame: 7 days
description: Severity Adverse Events
measure: Changes in toxicology index including mercury and arsenic on Day 7 of the treatment.
time frame: 7 days
description: toxicology index
measure: The proportion of the patients with Adverse Events within 7 and 90 days of the treatment.
time frame: 7 days, 90 days
description: Adverse Events
measure: The proportion of the patients with All-cause mortality within 7 and 90 days of the treatment.
time frame: 7 days, 90 days
description: All-cause mortality
measure: The proportion of the patients with Combined vascular events within 7 and 90 days of the treatment.
time frame: 7 days, 90 days
description: Combined vascular events
arm group label: AngongNiuhuang
arm group type: Experimental
description: Drugs : AngongNiuhuang pill. The other treatments will provided according to guidelines for standard treatment of acute ischemic stroke.
arm group label: Placebo of AngongNiuhuang
arm group type: Placebo Comparator
description: Drugs : Placebo of AngongNiuhuang pill. The other treatments will provided according to guidelines for standard treatment of acute ischemic stroke.
intervention type: Drug
intervention name: AngongNiuhuang pill
description: This group will receive AngongNiuhuang pill 1pill qd/day for 5-day.
arm group label: AngongNiuhuang
other name: Angong Niuhuang Wan
intervention type: Drug
intervention name: Placebo of AngongNiuhuang pill
description: This group will receive placebo of AngongNiuhuang pill 1pill qd/day for 5-day.
arm group label: Placebo of AngongNiuhuang
other name: Placebo of Angong Niuhuang Wan
intervention type: Other
intervention name: Standard treatment
description: The other treatments according to guidelines for standard treatment of acute ischemic stroke
arm group label: AngongNiuhuang
arm group label: Placebo of AngongNiuhuang
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bin Peng, MD
role: Principal Investigator
affiliation: Peking Union Medical College Hosptial, Chinese Academy of Medical Sciences
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Bin Peng
investigator title: Professor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
sharing ipd: No