<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/NCT03790800</url>
  </required_header>
  <id_info>
    <org_study_id>INTERACT4</org_study_id>
    <nct_id>NCT03790800</nct_id>
  </id_info>
  <brief_title>Intensive Ambulance-delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial</brief_title>
  <acronym>INTERACT4</acronym>
  <official_title>Intensive Ambulance-delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The George Institute for Global Health, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai East Hospital, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Chengdu Medical College, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The George Institute for Global Health, China</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>
      A multicentre, ambulance-delivered, prospective, randomized, open-label, blinded endpoint&#xD;
      (PROBE) study to assess the effects of hyperacute intensive blood pressure (BP) lowering&#xD;
      initiated in ambulance setting on (i) functional outcome in patients with acute stroke (ii)&#xD;
      safety in patients with confirmed acute stroke and other conditions that were initially&#xD;
      suspected as acute stroke (i.e. stroke mimic).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As an investigator initiated and conducted, multicentre, ambulance-delivered, prospective,&#xD;
      randomised, open-label, blinded outcome (PROBE) study. INTERACT4 aims to evaluate the effects&#xD;
      of functional outcome according to an ordinal analysis of the full range of scores on the&#xD;
      mRS, the safety in all randomised patients; reperfusion treatment (thrombolysis and/or&#xD;
      thrombectomy) related symptomatic ICH (sICH, according to standard definitions), infarct&#xD;
      size, the time to and overall rate of reperfusion treatment in AIS patients; hematoma volume&#xD;
      and early expansion in ICH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 20, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>central randomization with stratification</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Outcome assessor is independent of the treatment team</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>level of physical function</measure>
    <time_frame>Day 90</time_frame>
    <description>Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>number of patients with serious adverse events</measure>
    <time_frame>Day 90</time_frame>
    <description>total number of serious adverse events reported during follow-up, according to standard definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of patients with any intracranial hemorrhage</measure>
    <time_frame>Day 7</time_frame>
    <description>reperfusion treatment (thrombolysis/thrombectomy) related symptomatic intracerebral number of cases of intracranial hemorrhage, according to standard definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>size of cerebral infarction</measure>
    <time_frame>Day 2</time_frame>
    <description>overall size of cerebral infarction on MRI within 2 days in cases of ischaemic stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of patients who receive reperfusion treatment</measure>
    <time_frame>Day 0</time_frame>
    <description>total number of cases of reperfusion (thrombolysis and/or thrombectomy) in ischemic stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to use of reperfusion treatment</measure>
    <time_frame>Day 0</time_frame>
    <description>time from symptom onset to reperfusion treatment in patients with ischemic stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>size of hematoma volume</measure>
    <time_frame>Day 1</time_frame>
    <description>change in volume of hematoma from baseline to 24 hours, measured on brain imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>size of hematoma volume</measure>
    <time_frame>Day 0</time_frame>
    <description>volume of hematoma at baseline measured on brain imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>death or major disability</measure>
    <time_frame>Day 90</time_frame>
    <description>Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.&#xD;
mRS(3-6)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disability</measure>
    <time_frame>Day 90</time_frame>
    <description>Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>death or dependency measured by a shift in NIHSS</measure>
    <time_frame>day 1 and day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life</measure>
    <time_frame>day 90</time_frame>
    <description>according to the EQ-5D</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">2320</enrollment>
  <condition>Stroke, Acute</condition>
  <condition>Cerebrovascular Disorders</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>If systolic blood pressure&gt;180:IV Urapidil 25mg If systolic blood pressure&gt;150 (or 5 mins after first bolus) : IV Urapidil 25mg and to maintain this level after admission to hospital in those with confirmed acute stroke for the next 7 days (or hospital discharge if earlier)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>To receive blood pressure management according to standard local guidelines which recommend blood pressure lowering in hospital if systolic level is &gt;220mmHg. This level will be considered by ambulance staff as a threshold for treatment if considered clinically important.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>urapidil</intervention_name>
    <description>A standard treatment regime based on intravenous (IV) bolus of 25mg urapidil administered over 1 minute. For those patients initial systolic blood pressure 180, another 25mg urapidil bolus will be given if the systolic blood pressure level persists &gt;150 after 5 minutes.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Intensive BP lowing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age ≥18 years;&#xD;
&#xD;
          2. Acute syndrome that is due to presumed acute stroke, defined as FAST（Face, Arm,&#xD;
             Speech, Time） scores of ≥2 with an arm motor deficit and time ≤2 hours from last seen&#xD;
             well;&#xD;
&#xD;
          3. Systolic BP ≥150&#xD;
&#xD;
          4. Able to provide brief informed consent (if a waver of consent is not approved by the&#xD;
             ethics committee)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Coma - no response to tactile stimuli or verbal stimuli;&#xD;
&#xD;
          2. Severe co-morbid disease (e.g. cancer, chronic airflow disease, severe dementia,severe&#xD;
             heart failure,pre-stroke disability[needed help]);&#xD;
&#xD;
          3. History of epilepsy or seizure at onset;&#xD;
&#xD;
          4. History of recent head injury (&lt;7 days);&#xD;
&#xD;
          5. Hypoglycemia(glucose&lt;2.8mmol/L)&#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_official>
    <last_name>Craig Anderson</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute for Global Health, China</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gang Li</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital, China</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jie Yang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, China</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yapeng Lin</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affliated Hospital of Chengdu Medical College, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lily Song</last_name>
    <phone>+86 13916466400</phone>
    <email>lsong@georgeinstitute.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The George Institute for Global Health</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100088</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200123</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gang Li, MD</last_name>
      <phone>+86 18017187086</phone>
      <email>ligang@tongji.edu.cn</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital, China</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Yang</last_name>
      <phone>+86 13678130516</phone>
      <email>yangjie1126@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The First Affliated Hospital of Chengdu Medical College</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610500</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yapeng Lin</last_name>
      <phone>+86 13540389801</phone>
      <email>1009549973@qq.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The George Institute for Global Health, China</investigator_affiliation>
    <investigator_full_name>Craig Anderson</investigator_full_name>
    <investigator_title>Director, Global Brain Health program</investigator_title>
  </responsible_party>
  <keyword>stroke</keyword>
  <keyword>blood pressure control</keyword>
  <keyword>hypertension</keyword>
  <keyword>clinical trial</keyword>
  <keyword>ambulances</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Cerebrovascular Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urapidil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be shared with bona fide researchers after 1 year following conclusion of the study, based on a submitted protocol to the research office of The George Institute for Global Health, Sydney Australia</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>1 year after conclusion of the study</ipd_time_frame>
    <ipd_access_criteria>genuine researcher with supporting institution protocol review and approval by the research office of The George Institute</ipd_access_criteria>
    <ipd_url>http://georgeinstitute.org.au</ipd_url>
  </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/NCT03790800
org study id: INTERACT4
nct id: NCT03790800
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A multicentre, ambulance-delivered, prospective, randomized, open-label, blinded endpoint
      (PROBE) study to assess the effects of hyperacute intensive blood pressure (BP) lowering
      initiated in ambulance setting on (i) functional outcome in patients with acute stroke (ii)
      safety in patients with confirmed acute stroke and other conditions that were initially
      suspected as acute stroke (i.e. stroke mimic).
As an investigator initiated and conducted, multicentre, ambulance-delivered, prospective,
      randomised, open-label, blinded outcome (PROBE) study. INTERACT4 aims to evaluate the effects
      of functional outcome according to an ordinal analysis of the full range of scores on the
      mRS, the safety in all randomised patients; reperfusion treatment (thrombolysis and/or
      thrombectomy) related symptomatic ICH (sICH, according to standard definitions), infarct
      size, the time to and overall rate of reperfusion treatment in AIS patients; hematoma volume
      and early expansion in ICH.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: central randomization with stratification
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Outcome assessor is independent of the treatment team
measure: level of physical function
time frame: Day 90
description: Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
measure: number of patients with serious adverse events
time frame: Day 90
description: total number of serious adverse events reported during follow-up, according to standard definitions
measure: number of patients with any intracranial hemorrhage
time frame: Day 7
description: reperfusion treatment (thrombolysis/thrombectomy) related symptomatic intracerebral number of cases of intracranial hemorrhage, according to standard definitions
measure: size of cerebral infarction
time frame: Day 2
description: overall size of cerebral infarction on MRI within 2 days in cases of ischaemic stroke
measure: number of patients who receive reperfusion treatment
time frame: Day 0
description: total number of cases of reperfusion (thrombolysis and/or thrombectomy) in ischemic stroke
measure: time to use of reperfusion treatment
time frame: Day 0
description: time from symptom onset to reperfusion treatment in patients with ischemic stroke
measure: size of hematoma volume
time frame: Day 1
description: change in volume of hematoma from baseline to 24 hours, measured on brain imaging
measure: size of hematoma volume
time frame: Day 0
description: volume of hematoma at baseline measured on brain imaging
measure: death or major disability
time frame: Day 90
description: Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
mRS(3-6)
measure: Death
time frame: Day 90
measure: Disability
time frame: Day 90
description: Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
measure: death or dependency measured by a shift in NIHSS
time frame: day 1 and day 7
measure: Health related quality of life
time frame: day 90
description: according to the EQ-5D
arm group label: Intervention group
arm group type: Experimental
description: If systolic blood pressure>180:IV Urapidil 25mg If systolic blood pressure>150 (or 5 mins after first bolus) : IV Urapidil 25mg and to maintain this level after admission to hospital in those with confirmed acute stroke for the next 7 days (or hospital discharge if earlier)
arm group label: control group
arm group type: No Intervention
description: To receive blood pressure management according to standard local guidelines which recommend blood pressure lowering in hospital if systolic level is >220mmHg. This level will be considered by ambulance staff as a threshold for treatment if considered clinically important.
intervention type: Drug
intervention name: urapidil
description: A standard treatment regime based on intravenous (IV) bolus of 25mg urapidil administered over 1 minute. For those patients initial systolic blood pressure 180, another 25mg urapidil bolus will be given if the systolic blood pressure level persists >150 after 5 minutes.
arm group label: Intervention group
other name: Intensive BP lowing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Craig Anderson
role: Principal Investigator
affiliation: The George Institute for Global Health, China
last name: Gang Li
role: Principal Investigator
affiliation: Shanghai East Hospital, China
last name: Jie Yang
role: Principal Investigator
affiliation: Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China
last name: Yapeng Lin
role: Principal Investigator
affiliation: The First Affliated Hospital of Chengdu Medical College, China
last name: Lily Song
phone: +86 13916466400
email: lsong@georgeinstitute.org.cn
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: The George Institute for Global Health, China
investigator full name: Craig Anderson
investigator title: Director, Global Brain Health program
mesh term: Stroke
mesh term: Cerebrovascular Disorders
mesh term: Urapidil
sharing ipd: Yes
ipd description: Data will be shared with bona fide researchers after 1 year following conclusion of the study, based on a submitted protocol to the research office of The George Institute for Global Health, Sydney Australia
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: 1 year after conclusion of the study
ipd access criteria: genuine researcher with supporting institution protocol review and approval by the research office of The George Institute
ipd url: http://georgeinstitute.org.au