<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/NCT03838289</url>
  </required_header>
  <id_info>
    <org_study_id>cerebral vein</org_study_id>
    <nct_id>NCT03838289</nct_id>
  </id_info>
  <brief_title>Study of Cerebral Venous System in Acute Ischemic Stroke Patients Receiving Reperfusion Therapy</brief_title>
  <acronym>VAST</acronym>
  <official_title>Study of the Function of Cerebral Venous System in Acute Ischemic Stroke Patients Receiving Reperfusion Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</source>
  <oversight_info>
    <has_dmc>No</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>
      The VAST study is a single-center prospective observational study that enrolled individuals&#xD;
      with acute ischemic stroke (AIS) within 24 hours onset. The patients will receive&#xD;
      neurological examination, multimodal computed tomographic perfusion (CTP) or multimodal&#xD;
      magnetic resonance perfusion (MRP) before reperfusion therapy. The hypoperfusion volume,&#xD;
      ischemic core volume, brain edema, cerebral arterial collaterals will be evaluated on&#xD;
      baseline brain image. The status of cerebral venous system (CVs) including superficial middle&#xD;
      cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal&#xD;
      cerebral vein, Rosenthal's vein will be evaluated in phases of reconstructed imaging from&#xD;
      CTP/MRP. The investigators will explore the venous markers for prognosis of AIS patients who&#xD;
      received reperfusion therapy, and find the role of venous system in reperfusion injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stroke therapy had entered a new era since endovascular therapy was introduced in addition to&#xD;
      intravenous thrombolysis. The benefit of endovascular therapy for patients with a proven&#xD;
      proximal intracranial arterial occlusion has recently been revealed in several large&#xD;
      randomized controlled trials. However, a substantial number of patients treated with&#xD;
      reperfusion therapy did not reach functional independence in long-term follow-up, despite&#xD;
      relatively high recanalization rates. Therefore, simple and more reliable markers that&#xD;
      identify patients most likely to benefit from reperfusion therapy are needed. Accumulated&#xD;
      studies showed that arterial status such as arterial collaterals had been considered as a&#xD;
      critical predictor of outcome or determinant criteria for therapeutic selection. However,&#xD;
      other evidences denied that arterial collaterals serve as a predictors for outcome after&#xD;
      recanalization. Moreover, non-reflow phenomenon, over-reperfusion and futile recanalization&#xD;
      may lead to large infarct, brain swelling, hemorrhagic complication and neurological&#xD;
      deterioration. The traditional pathophysiological understanding on ischemic stroke can hardly&#xD;
      explain these occurrences. Recently, the importance of cerebral venous drainage, the major&#xD;
      blood reservoir and drainage system in brain, has been described for stroke evolution and&#xD;
      clinical sequelae. In this study, the aim is to investigate the roles of cerebral venous&#xD;
      dynamic status on neurological outcome after reperfusion therapy and the potential mechanisms&#xD;
      behind poor veins and adverse outcome. In this study, the investigators will prospectively&#xD;
      recruit the AIS patients over 18 years old who undergo baseline CTP/MRP and receive&#xD;
      reperfusion therapy within 24 hour after onset. Each of their perfusion imaging will be&#xD;
      reconstructed to evaluate the status of cerebral vein system. The investigators hypothesized&#xD;
      that the venous dynamic status may have effect on the ischemic-reperfusion progress, and may&#xD;
      thus has the potential to impact the stroke outcome. This study may add new implications for&#xD;
      stroke outcome prediction and future therapeutic decision-making.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prognosis</measure>
    <time_frame>90 days</time_frame>
    <description>modified Rankin Scale at 90 days:&#xD;
0 = No symptoms;&#xD;
1 = No significant disability. Able to carry out all usual activities, despite some symptoms;&#xD;
2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities;&#xD;
3 = Moderate disability. Requires some help, but able to walk unassisted;&#xD;
4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted;&#xD;
5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent;&#xD;
6 = Dead.&#xD;
A score of &gt;2 means poor outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brain edema</measure>
    <time_frame>24-hour</time_frame>
    <description>brain edema scale at 24-hour after reperfusion therapy:&#xD;
0 = indicates no swelling;&#xD;
1 = effacement of cortical sulci;&#xD;
2 = 1+minor effacement of the ipsilateral lateral ventricle;&#xD;
3 = 1+complete effacement of the ipsilateral lateral ventricle;&#xD;
4 = 3+effacement of the third ventricle;&#xD;
5 = shift of the midline away from the side of the infarction;&#xD;
6 = 5+effacement of basal cisterns.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemorrhage transformation</measure>
    <time_frame>24-hour</time_frame>
    <description>hemorrhage transformation at 24-hour after reperfusion therapy:&#xD;
Hemorrhagic infarction 1 (HI1) was defined as small petechiae along the margins of the infarct;&#xD;
Hemorrhagic infarction 2 (HI2) as confluent petechiae within the infarcted area but no space-occupying effect;&#xD;
Parenchymal hemorrhage (PH1) as blood clots in 30% or less of the infarcted area with some slight space-occupying effect; and&#xD;
Parenchymal hemorrhage (PH2) as blood clots in more than 30% of the infarcted area with substantial space-occupying effect.&#xD;
Symptomatic intracranial hemorrhage was defined as blood at any site in the brain on the CT scan.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Stroke</condition>
  <condition>Cerebral Venous System</condition>
  <condition>Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>Individuals with absent filling of CVs</arm_group_label>
    <description>Individuals with absent filling of following CVs: superficial middle cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal cerebral vein, Rosenthal's vein</description>
  </arm_group>
  <arm_group>
    <arm_group_label>individuals without any absent filling of CVs</arm_group_label>
    <description>Individuals without any absent filling of following CVs: superficial middle cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal cerebral vein, Rosenthal's vein</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>multimodal magnetic resonance imaging or computed tomography</intervention_name>
    <description>multimodal magnetic resonance imaging including T1 Flair,T2 Flair, magnetic resonance angiography (MRA), perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), enhanced gradient echo T2 star weighted angiography (ESWAN); multimodal computed tomography including non-contrast CT, volume perfusion CT</description>
    <arm_group_label>Individuals with absent filling of CVs</arm_group_label>
    <arm_group_label>individuals without any absent filling of CVs</arm_group_label>
    <other_name>blood samples collection</other_name>
    <other_name>neurological examination</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        acute ischemic stroke patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. receive reperfusion therapy within 24 hours after onset;&#xD;
&#xD;
          2. undergo multimodal magnetic resonance computed tomography before reperfusion therapy&#xD;
             and CTP or magnetic resonance perfusion at 24 hours after reperfusion therapy;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindication to imaging with contrast agents;&#xD;
&#xD;
          2. Without provision of informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Min Lou, Ph.D</last_name>
    <phone>13958007213</phone>
    <email>loumingxc@vip.sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The second affiliated hosipital of Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Min Lou, Ph.D</last_name>
      <phone>13958007213</phone>
      <email>loumingxc@vip.sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>April 16, 2023</last_update_submitted>
  <last_update_submitted_qc>April 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Reperfusion Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03838289
org study id: cerebral vein
nct id: NCT03838289
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The VAST study is a single-center prospective observational study that enrolled individuals
      with acute ischemic stroke (AIS) within 24 hours onset. The patients will receive
      neurological examination, multimodal computed tomographic perfusion (CTP) or multimodal
      magnetic resonance perfusion (MRP) before reperfusion therapy. The hypoperfusion volume,
      ischemic core volume, brain edema, cerebral arterial collaterals will be evaluated on
      baseline brain image. The status of cerebral venous system (CVs) including superficial middle
      cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal
      cerebral vein, Rosenthal's vein will be evaluated in phases of reconstructed imaging from
      CTP/MRP. The investigators will explore the venous markers for prognosis of AIS patients who
      received reperfusion therapy, and find the role of venous system in reperfusion injury.
Stroke therapy had entered a new era since endovascular therapy was introduced in addition to
      intravenous thrombolysis. The benefit of endovascular therapy for patients with a proven
      proximal intracranial arterial occlusion has recently been revealed in several large
      randomized controlled trials. However, a substantial number of patients treated with
      reperfusion therapy did not reach functional independence in long-term follow-up, despite
      relatively high recanalization rates. Therefore, simple and more reliable markers that
      identify patients most likely to benefit from reperfusion therapy are needed. Accumulated
      studies showed that arterial status such as arterial collaterals had been considered as a
      critical predictor of outcome or determinant criteria for therapeutic selection. However,
      other evidences denied that arterial collaterals serve as a predictors for outcome after
      recanalization. Moreover, non-reflow phenomenon, over-reperfusion and futile recanalization
      may lead to large infarct, brain swelling, hemorrhagic complication and neurological
      deterioration. The traditional pathophysiological understanding on ischemic stroke can hardly
      explain these occurrences. Recently, the importance of cerebral venous drainage, the major
      blood reservoir and drainage system in brain, has been described for stroke evolution and
      clinical sequelae. In this study, the aim is to investigate the roles of cerebral venous
      dynamic status on neurological outcome after reperfusion therapy and the potential mechanisms
      behind poor veins and adverse outcome. In this study, the investigators will prospectively
      recruit the AIS patients over 18 years old who undergo baseline CTP/MRP and receive
      reperfusion therapy within 24 hour after onset. Each of their perfusion imaging will be
      reconstructed to evaluate the status of cerebral vein system. The investigators hypothesized
      that the venous dynamic status may have effect on the ischemic-reperfusion progress, and may
      thus has the potential to impact the stroke outcome. This study may add new implications for
      stroke outcome prediction and future therapeutic decision-making.
observational model: Cohort
time perspective: Prospective
measure: Prognosis
time frame: 90 days
description: modified Rankin Scale at 90 days:
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.
A score of >2 means poor outcome.
measure: Brain edema
time frame: 24-hour
description: brain edema scale at 24-hour after reperfusion therapy:
0 = indicates no swelling;
1 = effacement of cortical sulci;
2 = 1+minor effacement of the ipsilateral lateral ventricle;
3 = 1+complete effacement of the ipsilateral lateral ventricle;
4 = 3+effacement of the third ventricle;
5 = shift of the midline away from the side of the infarction;
6 = 5+effacement of basal cisterns.
measure: Hemorrhage transformation
time frame: 24-hour
description: hemorrhage transformation at 24-hour after reperfusion therapy:
Hemorrhagic infarction 1 (HI1) was defined as small petechiae along the margins of the infarct;
Hemorrhagic infarction 2 (HI2) as confluent petechiae within the infarcted area but no space-occupying effect;
Parenchymal hemorrhage (PH1) as blood clots in 30% or less of the infarcted area with some slight space-occupying effect; and
Parenchymal hemorrhage (PH2) as blood clots in more than 30% of the infarcted area with substantial space-occupying effect.
Symptomatic intracranial hemorrhage was defined as blood at any site in the brain on the CT scan.
arm group label: Individuals with absent filling of CVs
description: Individuals with absent filling of following CVs: superficial middle cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal cerebral vein, Rosenthal's vein
arm group label: individuals without any absent filling of CVs
description: Individuals without any absent filling of following CVs: superficial middle cerebral vein, vein of Labbe, vein of Trolard, Sphenoid sinus, thalamostriate vein, Internal cerebral vein, Rosenthal's vein
intervention type: Radiation
intervention name: multimodal magnetic resonance imaging or computed tomography
description: multimodal magnetic resonance imaging including T1 Flair,T2 Flair, magnetic resonance angiography (MRA), perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), enhanced gradient echo T2 star weighted angiography (ESWAN); multimodal computed tomography including non-contrast CT, volume perfusion CT
arm group label: Individuals with absent filling of CVs
arm group label: individuals without any absent filling of CVs
other name: blood samples collection
other name: neurological examination
blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Min Lou, Ph.D
phone: 13958007213
email: loumingxc@vip.sina.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Reperfusion Injury
sharing ipd: Undecided