<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/NCT01702636</url>
  </required_header>
  <id_info>
    <org_study_id>NTA1201</org_study_id>
    <nct_id>NCT01702636</nct_id>
  </id_info>
  <brief_title>STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial</brief_title>
  <acronym>STOP-AUST</acronym>
  <official_title>STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neuroscience Trials Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neuroscience Trials Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to test if intracerebral haemorrhage (ICH) patients who have contrast&#xD;
      extravasation on computed tomography angiography, the &quot;spot sign&quot;, have lower rates of&#xD;
      haematoma growth when treated with tranexamic acid within 4.5 hours of stroke onset, compared&#xD;
      to placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">August 14, 2019</primary_completion_date>
  <phase>Phase 2</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>ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume.</measure>
    <time_frame>24+/-3 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism)</measure>
    <time_frame>Within 90+/-7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume</measure>
    <time_frame>24+/-3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute intraventricular haematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume</measure>
    <time_frame>24+/-3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>modified Rankin Scale (mRS) score of 0-4 at 3 months</measure>
    <time_frame>90+/-7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>modified Rankin Scale (mRS) score of 0-3 at 3 months</measure>
    <time_frame>90+/-7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption</measure>
    <time_frame>90+/-7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death due to any cause by 3 months</measure>
    <time_frame>within 90+/-7 days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>ICH growth</measure>
    <time_frame>24+/-3 hours</time_frame>
    <description>Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (&lt;3 vs. &gt;3 hours); baseline ICH volume (&lt;30 vs. &gt;30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (&gt;12 vs. 8-12) and age (&lt;70 vs. &gt;70). These analyses will be hypothesis generating, as the trial is not powered for them.</description>
  </other_outcome>
  <other_outcome>
    <measure>modified Rankin Scale (mRS)</measure>
    <time_frame>90+/-7 days</time_frame>
    <description>Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (&lt;3 vs. &gt;3 hours); baseline ICH volume (&lt;30 vs. &gt;30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (&gt;12 vs. 8-12) and age (&lt;70 vs. &gt;70). These analyses will be hypothesis generating, as the trial is not powered for them.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Intracerebral Haemorrhage</condition>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Tranexamic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous placebo in 100 mL 0.9% NaCl over 10 minutes followed by 500 mL 0.9% NaCl infusion over 8 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <arm_group_label>Tranexamic Acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients presenting with an acute ICH&#xD;
&#xD;
          -  Contrast extravasation within the haemorrhage, &quot;spot sign&quot;, evaluated from the CTA&#xD;
             according to three criteria, all of which must be present:&#xD;
&#xD;
               1. Serpiginous or spot-like appearance within the margin of a parenchymal haematoma&#xD;
                  without connection to an outside vessel;&#xD;
&#xD;
               2. The density (in Hounsfield units) should be greater than that of the background&#xD;
                  haematoma (site investigators are not required to document the density); and&#xD;
&#xD;
               3. No hyperdensity at the corresponding location on non-contrast CT.&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Treatment can commence within 1 hour of initial CT and within 4.5 hours of symptom&#xD;
             onset (or in patients with unknown time of symptom onset, the time patient was last&#xD;
             known to be well)&#xD;
&#xD;
          -  Informed consent has been received in accordance to local ethics committee&#xD;
             requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Glasgow coma scale (GCS) total score of &lt;8&#xD;
&#xD;
          -  Brainstem ICH&#xD;
&#xD;
          -  ICH volume &gt;70 ml as measured by the ABC/2 method&#xD;
&#xD;
          -  ICH known or suspected by study investigator to be secondary to trauma, aneurysm,&#xD;
             vascular malformation, haemorrhagic transformation of ischaemic stroke, cerebral&#xD;
             venous thrombosis, thrombolytic therapy, tumor, or infection&#xD;
&#xD;
          -  Contrast already administered within 24 hours prior to initial CT or contraindication&#xD;
             to imaging with CT contrast agents (e.g. known or suspected iodine allergy or&#xD;
             significant renal failure)&#xD;
&#xD;
          -  Any history or current evidence suggestive of venous or arterial thrombotic events&#xD;
             within the previous 12 months, including clinical, ECG, laboratory, or imaging&#xD;
             findings. Clinically silent chance findings of old ischemia are not considered&#xD;
             exclusion.&#xD;
&#xD;
          -  Hereditary or acquired haemorrhagic diathesis or coagulation factor deficiency.&#xD;
&#xD;
          -  Use of heparin, low-molecular weight heparin, GPIIb/IIIa antagonist, or oral&#xD;
             anticoagulation (e.g. warfarin, factor Xa inhibitor, thrombin inhibitor) within the&#xD;
             previous 14 days, irrespective of laboratory values&#xD;
&#xD;
          -  Pregnancy (women of childbearing potential must be tested)&#xD;
&#xD;
          -  Planned surgery for ICH within 24 hours&#xD;
&#xD;
          -  Concurrent or planned treatment with haemostatic agents (e.g. prothrombin complex&#xD;
             concentrate, vitamin K, fresh frozen plasma, or platelet transfusion)&#xD;
&#xD;
          -  Participation in any investigational study in the last 30 days&#xD;
&#xD;
          -  Known terminal illness or planned withdrawal of care or comfort care measures.&#xD;
&#xD;
          -  Any condition that, in the judgment of the investigator could impose hazards to the&#xD;
             patient if study therapy is initiated or affect the participation of the patient in&#xD;
             the study.&#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>Atte Meretoja, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Florey Institute of Neuroscience and Mental Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Geoffrey A Donnan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Florey Institute of Neuroscience and Mental Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephen M Davis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Melbourne Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gosford Hospital</name>
      <address>
        <city>Kanwal</city>
        <state>New South Wales</state>
        <zip>2259</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>Newcastle</city>
        <state>New South Wales</state>
        <zip>2310</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Box Hill Hospital</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Hospital</name>
      <address>
        <city>Footscray</city>
        <state>Victoria</state>
        <zip>3011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsinki University Central Hospital</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Finland</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>February 24, 2020</last_update_submitted>
  <last_update_submitted_qc>February 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intracerebral Hemorrhage</keyword>
  <keyword>ICH</keyword>
  <keyword>Stroke</keyword>
  <keyword>Cerebrovascular Disorders</keyword>
  <keyword>Brain Diseases</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Nervous System Diseases</keyword>
  <keyword>Vascular Diseases</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Tranexamic Acid</keyword>
  <keyword>Antifibrinolytic Agents</keyword>
  <keyword>Fibrin Modulating Agents</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Cardiovascular Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Hematologic Agents</keyword>
  <keyword>Hemostatics</keyword>
  <keyword>Contrast Media</keyword>
  <keyword>Angiography</keyword>
  <keyword>Cerebral Angiography</keyword>
  <keyword>Tomography, X-Ray Computed</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tranexamic Acid</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01702636
org study id: NTA1201
nct id: NCT01702636
lead sponsor: 
has dmc: Yes
The aim of the study is to test if intracerebral haemorrhage (ICH) patients who have contrast
      extravasation on computed tomography angiography, the "spot sign", have lower rates of
      haematoma growth when treated with tranexamic acid within 4.5 hours of stroke onset, compared
      to placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ICH growth by 24±3 hours as defined by either 33% or 6 ml increase from baseline, adjusted for baseline ICH volume.
time frame: 24+/-3 hours
measure: Major thromboembolic events (myocardial infarction, ischaemic stroke, pulmonary embolism)
time frame: Within 90+/-7 days
measure: Absolute ICH growth volume by 24±3 hours, adjusted for baseline ICH volume
time frame: 24+/-3 hours
measure: Absolute intraventricular haematoma (IVH) growth volume by 24±3 hours, adjusted for baseline IVH volume
time frame: 24+/-3 hours
measure: modified Rankin Scale (mRS) score of 0-4 at 3 months
time frame: 90+/-7 days
measure: modified Rankin Scale (mRS) score of 0-3 at 3 months
time frame: 90+/-7 days
measure: Categorical shift in mRS at 3 months, subject to the validity of proportional odds assumption
time frame: 90+/-7 days
measure: Death due to any cause by 3 months
time frame: within 90+/-7 days
measure: ICH growth
time frame: 24+/-3 hours
description: Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (<3 vs. >3 hours); baseline ICH volume (<30 vs. >30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (>12 vs. 8-12) and age (<70 vs. >70). These analyses will be hypothesis generating, as the trial is not powered for them.
measure: modified Rankin Scale (mRS)
time frame: 90+/-7 days
description: Exploratory analyses will be run with adjustments for baseline variables such as age, Glasgow Coma Scale (GCS), presence of IVH, and ICH location, and in the following subgroups: onset-to-treatment time (<3 vs. >3 hours); baseline ICH volume (<30 vs. >30 ml); anatomical location (deep, lobar, or cerebellar); IVH (absent vs. present); GCS (>12 vs. 8-12) and age (<70 vs. >70). These analyses will be hypothesis generating, as the trial is not powered for them.
arm group label: Tranexamic Acid
arm group type: Active Comparator
description: Intravenous tranexamic acid 1000 mg in 100 mL 0.9% NaCl over 10 minutes followed by 1000 mg in 500 mL 0.9% NaCl infusion over 8 hours.
arm group label: Placebo
arm group type: Placebo Comparator
description: Intravenous placebo in 100 mL 0.9% NaCl over 10 minutes followed by 500 mL 0.9% NaCl infusion over 8 hours.
intervention type: Drug
intervention name: Tranexamic Acid
arm group label: Tranexamic Acid
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Atte Meretoja, MD
role: Principal Investigator
affiliation: The Florey Institute of Neuroscience and Mental Health
last name: Geoffrey A Donnan, MD
role: Principal Investigator
affiliation: The Florey Institute of Neuroscience and Mental Health
last name: Stephen M Davis, MD
role: Principal Investigator
affiliation: Melbourne Health
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Finland
responsible party type: Sponsor
mesh term: Cerebral Hemorrhage
mesh term: Hemorrhage
mesh term: Tranexamic Acid