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/NCT05976152</url>
    </required_header>
    <id_info>
      <org_study_id>Be-CLEVER</org_study_id>
      <nct_id>NCT05976152</nct_id>
    </id_info>
    <brief_title>Effect of Butyphthalide on Cognitive Level Change After Cerebral Vascular Event-a Randomized Control Trial (Be-CLEVER)</brief_title>
    <acronym>Be-CLEVER</acronym>
    <official_title>Effect of Butyphthalide on Cognitive Level Change After Cerebral Vascular Event-a Randomized Control Trial (Be-CLEVER)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan 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>
        Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome characterized by&#xD;
        cognitive impairment that occurs after a stroke event and persists for at least 6 months. Due&#xD;
        to the early recovery of conditions such as delirium and transient cognitive impairment after&#xD;
        stroke, the diagnosis of PSCI often requires cognitive assessment at 3 to 6 months&#xD;
        post-stroke to determine the severity of cognitive impairment. It can be classified according&#xD;
        to the severity of cognitive impairment as post-stroke cognitive impairment no dementia&#xD;
        (PSCIND) and post-stroke dementia (PSD). Recent large international cohort studies have&#xD;
        reported an incidence rate of PSCI ranging from 24% to 53.4%, and patients with PSCI have a&#xD;
        significantly higher mortality rate compared to those without cognitive impairment.&#xD;
        Guidelines such as American Heart Association/American Society of Anesthesiologists (AHA/ASA)&#xD;
        and the Chinese &quot;Expert Consensus on the Management of Post-Stroke Cognitive Impairment&quot;&#xD;
        propose integrating cognitive impairment and stroke intervention strategies. Early&#xD;
        comprehensive intervention and treatment for high-risk individuals after stroke, aiming to&#xD;
        delay or prevent the progression from PSCIND to PSD, are the primary goals in the current&#xD;
        treatment of PSCI. However, there is currently a lack of large randomized controlled trials&#xD;
        (RCTs) for PSCI, and research is still needed to determine whether cognitive-enhancing drugs&#xD;
        can reduce the risk of PSCI occurrence and improve outcomes and prognosis for PSCI patients.&#xD;
        A randomized, double-blind, multicenter clinical study involving 281 non-dementia vascular&#xD;
        cognitive impairment (VCI) patients showed that the overall cognitive scores of patients&#xD;
        treated with donepezil for 6 months significantly improved compared to the placebo group.&#xD;
  &#xD;
        The aim of this study is to evaluate the effectiveness of donepezil in the treatment of&#xD;
        post-stroke cognitive impairment. It will be a multicenter, randomized, double-blind,&#xD;
        placebo-controlled trial with a 48-week treatment duration. The study will observe the&#xD;
        difference in PSCI incidence rate between the donepezil treatment group and the conventional&#xD;
        stroke treatment group at 24 weeks and evaluate the improvement in post-stroke cognitive&#xD;
        impairment after 6 months of donepezil treatment compared to conventional treatment.&#xD;
  &#xD;
        This study will be conducted in two stages: the first stage (0-6 months) aims to assess&#xD;
        whether donepezil can reduce the risk of PSCI occurrence and will be a multicenter,&#xD;
        randomized, double-blind, placebo-controlled study. The second stage (7-12 months) aims to&#xD;
        evaluate whether donepezil can improve the prognosis of PSCI patients and will also be a&#xD;
        multicenter, randomized, double-blind, placebo-controlled study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>PSCI incidence</measure>
      <time_frame>24 weeks (first stage)</time_frame>
      <description>Compared with routine stroke treatment, the difference of the PSCI incidence at 24 weeks with butylphthalide treatment.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>vadas-cog score</measure>
      <time_frame>6 months (Second stage)</time_frame>
      <description>Compared with routine treatment, improvement of vadas-cog scores at 6 months with butylphthalide treatment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes of Montreal Cognitive Assessment (MoCA) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Montreal Cognitive Assessment (MoCA) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Mini-Mental State Examination (MMSE) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Mini-Mental State Examination (MMSE) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Hamilton Anxiety Scale (HAMA) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Hamilton Anxiety Scale (HAMA) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Hamilton Depression Scale (HAMD) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Hamilton Depression Scale (HAMD) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Clinical Dementia Rating (CDR) at 6 months compared with baseline</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Changes of Clinical Dementia Rating (CDR) at 6 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of infarct volume by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.</measure>
      <time_frame>24 weeks (first stage)</time_frame>
      <description>Changes of infarct volume by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of infarct location by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.</measure>
      <time_frame>24 weeks (first stage)</time_frame>
      <description>Changes of infarct location by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>stroke recurrence</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>Difference in stroke recurrence rate of butylphthalein treatment compared with routine stroke treatment at 6 months</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of modified Rankin Scale score (mRS) at 6 months compared with baseline.</measure>
      <time_frame>6 months (first stage)</time_frame>
      <description>The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Montreal Cognitive Assessment (MoCA) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Montreal Cognitive Assessment (MoCA) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Mini-Mental State Examination (MMSE) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Mini-Mental State Examination (MMSE) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes cognitive domain level by Symbol Digit Modalities Test at 12 months compared with baselinel</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes cognitive domain level by Symbol Digit Modalities Test at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes cognitive domain level by Trail Making Test at 12 months compared with baseline.</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes cognitive domain level by Trail Making Test at 12 months compared with baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Hamilton Anxiety Scale (HAMA) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Hamilton Anxiety Scale (HAMA) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Hamilton Depression Scale (HAMD) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Hamilton Depression Scale (HAMD) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of Clinical Dementia Rating (CDR) at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of Clinical Dementia Rating (CDR) at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 12 months compared with baseline</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 12 months compared with baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>stroke recurrence</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>Difference in stroke recurrence rate of butylphthalein treatment compared with routine stroke treatment at 12 months</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of mRS at 12 months compared with baseline.</measure>
      <time_frame>12 months (second stage)</time_frame>
      <description>The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 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</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events [Safety]</measure>
      <time_frame>3 months, 6 months, 9 months and 12 months</time_frame>
      <description>Incidence of Treatment-Emergent Adverse Events [Safety]</description>
    </other_outcome>
    <other_outcome>
      <measure>Dropout rates and reasons [Safety]</measure>
      <time_frame>3 months, 6 months, 9 months and 12 months</time_frame>
      <description>Dropout rates and reasons [Safety]</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">3200</enrollment>
    <condition>Stroke</condition>
    <condition>Post-stroke Cognitive Impairment (PSCI)</condition>
    <arm_group>
      <arm_group_label>dl-3-butylphthalide</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Routine treatment and dl-3-butylphthalide</description>
    </arm_group>
    <arm_group>
      <arm_group_label>dl-3-butylphthalide Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Routine treatment and dl-3-butylphthalide Placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>dl-3-butylphthalide</intervention_name>
      <description>First stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs.&#xD;
  Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Butylphthalide group:&#xD;
  Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.</description>
      <arm_group_label>dl-3-butylphthalide</arm_group_label>
      <arm_group_label>dl-3-butylphthalide Placebo</arm_group_label>
      <other_name>DL-3-n-butylphthalide (NBP)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>dl-3-butylphthalide placebo</intervention_name>
      <description>First stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs.&#xD;
  Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.&#xD;
  Butylphthalide group:&#xD;
  Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.</description>
      <arm_group_label>dl-3-butylphthalide</arm_group_label>
      <arm_group_label>dl-3-butylphthalide Placebo</arm_group_label>
      <other_name>NBP placebo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          First stage:&#xD;
  &#xD;
            -  Acute ischemic stroke (AIS) symptom onset within 14 days Signs and symptoms consistent&#xD;
               with the diagnosis of an acute ischemic stroke by CT/MRI.&#xD;
  &#xD;
            -  Age &gt;= 60 years，&#xD;
  &#xD;
            -  Baseline NIHSS 3-18.&#xD;
  &#xD;
            -  Patient can complete questionnaire survey, physical examination, cranial MRI and other&#xD;
               medical examinations&#xD;
  &#xD;
            -  Patient/legally authorized representative has signed the Informed Consent Form&#xD;
  &#xD;
          Second stage:&#xD;
  &#xD;
            -  Patient with stage I diagnosis of PSCI.&#xD;
  &#xD;
            -  Patient can complete questionnaire survey, physical examination, cranial MRI and other&#xD;
               medical examinations.&#xD;
  &#xD;
            -  Patient/legally authorized representative has signed the Informed Consent Form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          First stage:&#xD;
  &#xD;
            -  Patients who had been diagnosed with dementia prior to stroke&#xD;
  &#xD;
            -  Other related factors affecting cognitive function: central nervous system infection,&#xD;
               neurodegenerative diseases, trauma, poisoning, intracranial space occupying lesions,&#xD;
               metabolic diseases, etc.&#xD;
  &#xD;
            -  Other serious central nervous system diseases: Parkinson's disease, epilepsy, multiple&#xD;
               sclerosis, motor neurone disease, immune-related encephalomyelopathy, etc.&#xD;
  &#xD;
            -  Serious mental illness: anxiety disorder, depression, delirium, schizophrenia, bipolar&#xD;
               disorder, mental retardation, which is diagnosed or controlled by medication.&#xD;
  &#xD;
            -  Uncorrectable visual and hearing impairments and inability to complete&#xD;
               neuropsychological tests&#xD;
  &#xD;
            -  Severe liver and kidney dysfunction&#xD;
  &#xD;
            -  The presence of a malignant tumor or other serious/life-threatening disease that could&#xD;
               cause the subject's death within 12 months.&#xD;
  &#xD;
            -  Current known alcohol or illicit drug abuse or dependence&#xD;
  &#xD;
            -  Patients undergoing thrombectomy, thrombolysis, carotid endarterectomy, or other&#xD;
               surgical procedures during the acute infarction.&#xD;
  &#xD;
            -  Using cholinesterase inhibitors, N-methyl-D-aspartate (NMDA) receptor antagonists, or&#xD;
               Sodium oligomannate (GV-971).&#xD;
  &#xD;
            -  Allergic to any component of butylphthalein&#xD;
  &#xD;
            -  Pregnancy or lactation, have the possibility of becoming pregnant, and who plan to&#xD;
               become pregnant&#xD;
  &#xD;
            -  Participants in other interventional clinical trials&#xD;
  &#xD;
            -  MRI contraindications (e.g., claustrophobia, hypersensitivity to contrast media, etc.)&#xD;
  &#xD;
          Second stage:&#xD;
  &#xD;
            -  Patients did not take the study drug as prescribed, or discontinued the study drug,&#xD;
               and were followed up for less than 24 weeks in the first stage.&#xD;
  &#xD;
            -  Recurrent stroke in the first stage&#xD;
  &#xD;
            -  Use drugs that may affect cognitive function&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Qiang Dong</last_name>
      <phone>+8602152887145</phone>
      <email>dong_qiang@fudan.edu.cn</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 6, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Huashan Hospital</investigator_affiliation>
      <investigator_full_name>Qiang Dong</investigator_full_name>
      <investigator_title>Director of Neurology Department, Huashan Hospital</investigator_title>
    </responsible_party>
    <keyword>stroke</keyword>
    <keyword>PSCI</keyword>
    <keyword>Butylphthalide</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>3-n-butylphthalide</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/NCT05976152
  org study id: Be-CLEVER
  nct id: NCT05976152
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome characterized by
        cognitive impairment that occurs after a stroke event and persists for at least 6 months. Due
        to the early recovery of conditions such as delirium and transient cognitive impairment after
        stroke, the diagnosis of PSCI often requires cognitive assessment at 3 to 6 months
        post-stroke to determine the severity of cognitive impairment. It can be classified according
        to the severity of cognitive impairment as post-stroke cognitive impairment no dementia
        (PSCIND) and post-stroke dementia (PSD). Recent large international cohort studies have
        reported an incidence rate of PSCI ranging from 24% to 53.4%, and patients with PSCI have a
        significantly higher mortality rate compared to those without cognitive impairment.
        Guidelines such as American Heart Association/American Society of Anesthesiologists (AHA/ASA)
        and the Chinese "Expert Consensus on the Management of Post-Stroke Cognitive Impairment"
        propose integrating cognitive impairment and stroke intervention strategies. Early
        comprehensive intervention and treatment for high-risk individuals after stroke, aiming to
        delay or prevent the progression from PSCIND to PSD, are the primary goals in the current
        treatment of PSCI. However, there is currently a lack of large randomized controlled trials
        (RCTs) for PSCI, and research is still needed to determine whether cognitive-enhancing drugs
        can reduce the risk of PSCI occurrence and improve outcomes and prognosis for PSCI patients.
        A randomized, double-blind, multicenter clinical study involving 281 non-dementia vascular
        cognitive impairment (VCI) patients showed that the overall cognitive scores of patients
        treated with donepezil for 6 months significantly improved compared to the placebo group.
  
        The aim of this study is to evaluate the effectiveness of donepezil in the treatment of
        post-stroke cognitive impairment. It will be a multicenter, randomized, double-blind,
        placebo-controlled trial with a 48-week treatment duration. The study will observe the
        difference in PSCI incidence rate between the donepezil treatment group and the conventional
        stroke treatment group at 24 weeks and evaluate the improvement in post-stroke cognitive
        impairment after 6 months of donepezil treatment compared to conventional treatment.
  
        This study will be conducted in two stages: the first stage (0-6 months) aims to assess
        whether donepezil can reduce the risk of PSCI occurrence and will be a multicenter,
        randomized, double-blind, placebo-controlled study. The second stage (7-12 months) aims to
        evaluate whether donepezil can improve the prognosis of PSCI patients and will also be a
        multicenter, randomized, double-blind, placebo-controlled study.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: PSCI incidence
  time frame: 24 weeks (first stage)
  description: Compared with routine stroke treatment, the difference of the PSCI incidence at 24 weeks with butylphthalide treatment.
  measure: vadas-cog score
  time frame: 6 months (Second stage)
  description: Compared with routine treatment, improvement of vadas-cog scores at 6 months with butylphthalide treatment
  measure: Changes of Montreal Cognitive Assessment (MoCA) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Montreal Cognitive Assessment (MoCA) at 6 months compared with baseline
  measure: Changes of Mini-Mental State Examination (MMSE) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Mini-Mental State Examination (MMSE) at 6 months compared with baseline
  measure: Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 6 months compared with baseline
  measure: Changes of Hamilton Anxiety Scale (HAMA) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Hamilton Anxiety Scale (HAMA) at 6 months compared with baseline
  measure: Changes of Hamilton Depression Scale (HAMD) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Hamilton Depression Scale (HAMD) at 6 months compared with baseline
  measure: Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 6 months compared with baseline
  measure: Changes of Clinical Dementia Rating (CDR) at 6 months compared with baseline
  time frame: 6 months (first stage)
  description: Changes of Clinical Dementia Rating (CDR) at 6 months compared with baseline
  measure: Changes of infarct volume by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.
  time frame: 24 weeks (first stage)
  description: Changes of infarct volume by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.
  measure: Changes of infarct location by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.
  time frame: 24 weeks (first stage)
  description: Changes of infarct location by cranial magnetic resonance imaging (MRI) at 24 weeks after treatment with butylphthalein compared with routine stroke treatment.
  measure: stroke recurrence
  time frame: 6 months (first stage)
  description: Difference in stroke recurrence rate of butylphthalein treatment compared with routine stroke treatment at 6 months
  measure: Changes of modified Rankin Scale score (mRS) at 6 months compared with baseline.
  time frame: 6 months (first stage)
  description: The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 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
  measure: Changes of Montreal Cognitive Assessment (MoCA) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Montreal Cognitive Assessment (MoCA) at 12 months compared with baseline
  measure: Changes of Mini-Mental State Examination (MMSE) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Mini-Mental State Examination (MMSE) at 12 months compared with baseline
  measure: Changes cognitive domain level by Symbol Digit Modalities Test at 12 months compared with baselinel
  time frame: 12 months (second stage)
  description: Changes cognitive domain level by Symbol Digit Modalities Test at 12 months compared with baseline
  measure: Changes cognitive domain level by Trail Making Test at 12 months compared with baseline.
  time frame: 12 months (second stage)
  description: Changes cognitive domain level by Trail Making Test at 12 months compared with baseline.
  measure: Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Neuropsychiatric Inventory Questionnaire (NPI-Q) at 12 months compared with baseline
  measure: Changes of Hamilton Anxiety Scale (HAMA) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Hamilton Anxiety Scale (HAMA) at 12 months compared with baseline
  measure: Changes of Hamilton Depression Scale (HAMD) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Hamilton Depression Scale (HAMD) at 12 months compared with baseline
  measure: Changes of Clinical Dementia Rating (CDR) at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of Clinical Dementia Rating (CDR) at 12 months compared with baseline
  measure: Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 12 months compared with baseline
  time frame: 12 months (second stage)
  description: Changes of 23-item version of Alzheimer's Disease Cooperative Study- activities of daily living scale (ADCS-ADL23) for activities of daily living at 12 months compared with baseline
  measure: stroke recurrence
  time frame: 12 months (second stage)
  description: Difference in stroke recurrence rate of butylphthalein treatment compared with routine stroke treatment at 12 months
  measure: Changes of mRS at 12 months compared with baseline.
  time frame: 12 months (second stage)
  description: The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 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
  measure: Incidence of Treatment-Emergent Adverse Events [Safety]
  time frame: 3 months, 6 months, 9 months and 12 months
  description: Incidence of Treatment-Emergent Adverse Events [Safety]
  measure: Dropout rates and reasons [Safety]
  time frame: 3 months, 6 months, 9 months and 12 months
  description: Dropout rates and reasons [Safety]
  arm group label: dl-3-butylphthalide
  arm group type: Experimental
  description: Routine treatment and dl-3-butylphthalide
  arm group label: dl-3-butylphthalide Placebo
  arm group type: Placebo Comparator
  description: Routine treatment and dl-3-butylphthalide Placebo
  intervention type: Drug
  intervention name: dl-3-butylphthalide
  description: First stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs.
  Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Butylphthalide group:
  Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  arm group label: dl-3-butylphthalide
  arm group label: dl-3-butylphthalide Placebo
  other name: DL-3-n-butylphthalide (NBP)
  intervention type: Drug
  intervention name: dl-3-butylphthalide placebo
  description: First stage： Routine stroke treatment: hypoglycemic, antihypertensive, antiplatelet, anticoagulant and other conventional cerebrovascular disease treatment drugs.
  Placebo group: routine stroke treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Butylphthalide group: routine stroke treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Second stage： 14d washout period after first stage. Routine PSCI treatment: 5-10 mg Donepezil, qd. Placebo group: Routine PSCI treatment + oral Butylphthalide Placebo Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  Butylphthalide group:
  Routine PSCI treatment + oral Butylphthalide Soft Capsules, 2 capsules/time, tid, an empty stomach for 6 months.
  arm group label: dl-3-butylphthalide
  arm group label: dl-3-butylphthalide Placebo
  other name: NBP placebo
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Qiang Dong
  phone: +8602152887145
  email: dong_qiang@fudan.edu.cn
  responsible party type: Principal Investigator
  investigator affiliation: Huashan Hospital
  investigator full name: Qiang Dong
  investigator title: Director of Neurology Department, Huashan Hospital
  mesh term: Stroke
  mesh term: 3-n-butylphthalide