<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/NCT03287076</url>
  </required_header>
  <id_info>
    <org_study_id>NTA1127</org_study_id>
    <secondary_id>2018-004325-88</secondary_id>
    <nct_id>NCT03287076</nct_id>
  </id_info>
  <brief_title>Trial of EXenatide in Acute Ischaemic Stroke</brief_title>
  <acronym>TEXAIS</acronym>
  <official_title>A Multicentre, Randomised Controlled Trial of Exenatide Versus Standard Care in Acute Ischemic Stroke (TEXAIS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neuroscience Trials Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Monash University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Neuroscience Trials Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multicentre, randomised controlled Trial of Exenatide versus standard care in Acute&#xD;
      Ischemic Stroke&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overview: Elevated blood glucose levels are common in many acute diseases, resulting in worse&#xD;
      clinical outcomes. Hyperglycaemia in acute ischaemic stroke (post-stroke hyperglycaemia&#xD;
      [PSH]) occurs in up to 50% patients, reduces the efficacy of stroke thrombolysis with&#xD;
      increased risk of haemorrhage, increases infarct size, and results in worse clinical outcomes&#xD;
      and death. Insulin-based therapies have not proved beneficial in treating PSH: they are&#xD;
      difficult to implement and maintain, cause frequent hypoglycaemia, may cause increased&#xD;
      infarct size, and do not reduce mortality or improve clinical outcomes. An alternative,&#xD;
      simple to use, treatment for PSH may therefore have a significant impact not only for acute&#xD;
      stroke care, but in other acute diseases.&#xD;
&#xD;
      Pilot data: Exenatide is a commonly used diabetes drug (a synthetic glucagon- like peptide-1&#xD;
      receptor agonist) that increases insulin secretion. Importantly, this action is glucose&#xD;
      dependent - as blood glucose levels decrease, its stimulatory effect on insulin secretion&#xD;
      subsides, with a very low risk of hypoglycaemia. A small randomised pilot study of 17&#xD;
      consecutive, unselected patients (ie. regardless of their admission glucose level) with acute&#xD;
      ischaemic stroke compared subcutaneous exenatide 5μg for 5 days with routine standard of&#xD;
      care. Overall, blood glucose levels remained consistently lower (and less variable) in the&#xD;
      exenatide group, and most noticeably in those stroke patients with known diabetes. Exenatide&#xD;
      was safe and well tolerated by all patients, with no symptomatic hypoglycaemia.&#xD;
&#xD;
      Trial design: TEXAIS is a 3 year Phase 2, multi centre, prospective, randomised, open label,&#xD;
      blinded end-point (PROBE) trial comparing Exenatide to Standard of Care. The sample size is&#xD;
      528 patients (264 in each arm).&#xD;
&#xD;
      Intervention: Treatment arm will receive Exenatide (Byetta) 5μg subcutaneously twice daily&#xD;
      for five days, commencing within 9 hours of symptom onset. Stroke onset time for wake-up&#xD;
      strokes is taken as mid-point between going to bed, and waking up. Antiemetic therapy&#xD;
      (metoclopramide or ondansetron) will be commenced with the first dose of Exenatide. In&#xD;
      patients receiving tPA, Exenatide will be given alongside, or as soon as possible, following&#xD;
      tPA administration (within 60 minutes). Diabetic patients already on oral agents and/or&#xD;
      insulin may continue these (as per standard practice) in addition to Exenatide. Continuous&#xD;
      glucose monitors (CGMs) will track the intra-day dynamic variability of glucose in acute&#xD;
      stroke.&#xD;
&#xD;
      Translation: TEXAIS is a simple, practical, study that can enrol all patients with ischaemic&#xD;
      stroke, regardless of admission blood glucose level, regardless of stroke severity, with no&#xD;
      target glucose level, and with low risk of hypoglycaemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 23, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 4, 2021</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>improved neurological outcome</measure>
    <time_frame>7 days</time_frame>
    <description>Treatment with short acting Exenatide (Byetta) in patients with acute ischaemic stroke is hypothesised to improve neurological outcome as measured by ≥8 point improvement in the National Institutes of Health Stroke Scale (NIHSS) stroke disability score (or NIHSS 0-1) at 7 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>post stroke hyperglycaemia</measure>
    <time_frame>90 days</time_frame>
    <description>reduce the occurrence of post stroke hyperglycaemia (&gt;7mmol/l).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale</measure>
    <time_frame>90 days</time_frame>
    <description>improve Modified Rankin Scale (mRS) at 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIHSS</measure>
    <time_frame>90 days</time_frame>
    <description>improve NIHSS at 90 days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">350</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive exenatide injections</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard care for stroke as per hospital protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide Injection</intervention_name>
    <description>5μg subcutaneously twice daily for five days, commencing within 9 hours of symptom onset</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>Byetta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females 18 years or older&#xD;
&#xD;
          -  Acute Ischaemic Stroke - CT brain exclusion of haemorrhagic stroke&#xD;
&#xD;
          -  Blood glucose level on admission ≥ 4mmol/L&#xD;
&#xD;
          -  First trial treatment possible within 9 hours of stroke onset&#xD;
&#xD;
          -  Pre-morbid /mRS score of 0-2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Haemorrhagic stroke&#xD;
&#xD;
          -  Poor clinical prognosis /palliation (considered unlikely to survive beyond 14 days&#xD;
             post stroke).&#xD;
&#xD;
          -  Any known allergy or hypersensitivity to Exenatide&#xD;
&#xD;
          -  Females who are pregnant (known or suspected) or currently breastfeeding&#xD;
&#xD;
          -  Any past history of pancreatitis or evidence of active pancreatitis&#xD;
&#xD;
          -  History of active severe gastrointestinal disease (including but not limited to&#xD;
             gastroparesis and dumping syndrome)&#xD;
&#xD;
          -  Current chronic kidney disease stage 4 or 5 (creatinine clearance &lt;30ml/min)&#xD;
&#xD;
          -  Current participation in another interventional clinical trial&#xD;
&#xD;
          -  Inability to provide consent (participant or person responsible as local laws apply)&#xD;
&#xD;
          -  Current use of Exenatide (Byetta®), or other GLP-1 agonist diabetes medication&#xD;
&#xD;
          -  Patients considered unlikely to be able to be followed up at 3 months (including but&#xD;
             not limited to geographical location of patient at 3 months)&#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>Christopher Bladin</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Florey Institute of Neuroscience &amp; Mental Health Melbourne Brain Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Vincent's Hospital Sydney</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunshine Coast University Hospital</name>
      <address>
        <city>Birtinya</city>
        <state>Queensland</state>
        <zip>4575</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Launceston General Hospital</name>
      <address>
        <city>Launceston</city>
        <state>Tasmania</state>
        <zip>7250</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>St Vincent's Hospital Melbourne</name>
      <address>
        <city>Fitzroy</city>
        <state>Victoria</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Hospital</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John of God Midland Public &amp; Private Hospital</name>
      <address>
        <city>Midland</city>
        <state>Western Australia</state>
        <zip>6056</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsinki University Hospital</name>
      <address>
        <city>Helsinki</city>
        <zip>00290</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CDHB Christchurch Hospital</name>
      <address>
        <city>Christchurch</city>
        <zip>8140</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Finland</country>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>September 7, 2021</last_update_submitted>
  <last_update_submitted_qc>September 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>stroke</keyword>
  <keyword>glucose</keyword>
  <keyword>exenatide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exenatide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03287076
org study id: NTA1127
secondary id: 2018-004325-88
nct id: NCT03287076
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
A multicentre, randomised controlled Trial of Exenatide versus standard care in Acute
      Ischemic Stroke
Overview: Elevated blood glucose levels are common in many acute diseases, resulting in worse
      clinical outcomes. Hyperglycaemia in acute ischaemic stroke (post-stroke hyperglycaemia
      [PSH]) occurs in up to 50% patients, reduces the efficacy of stroke thrombolysis with
      increased risk of haemorrhage, increases infarct size, and results in worse clinical outcomes
      and death. Insulin-based therapies have not proved beneficial in treating PSH: they are
      difficult to implement and maintain, cause frequent hypoglycaemia, may cause increased
      infarct size, and do not reduce mortality or improve clinical outcomes. An alternative,
      simple to use, treatment for PSH may therefore have a significant impact not only for acute
      stroke care, but in other acute diseases.

      Pilot data: Exenatide is a commonly used diabetes drug (a synthetic glucagon- like peptide-1
      receptor agonist) that increases insulin secretion. Importantly, this action is glucose
      dependent - as blood glucose levels decrease, its stimulatory effect on insulin secretion
      subsides, with a very low risk of hypoglycaemia. A small randomised pilot study of 17
      consecutive, unselected patients (ie. regardless of their admission glucose level) with acute
      ischaemic stroke compared subcutaneous exenatide 5μg for 5 days with routine standard of
      care. Overall, blood glucose levels remained consistently lower (and less variable) in the
      exenatide group, and most noticeably in those stroke patients with known diabetes. Exenatide
      was safe and well tolerated by all patients, with no symptomatic hypoglycaemia.

      Trial design: TEXAIS is a 3 year Phase 2, multi centre, prospective, randomised, open label,
      blinded end-point (PROBE) trial comparing Exenatide to Standard of Care. The sample size is
      528 patients (264 in each arm).

      Intervention: Treatment arm will receive Exenatide (Byetta) 5μg subcutaneously twice daily
      for five days, commencing within 9 hours of symptom onset. Stroke onset time for wake-up
      strokes is taken as mid-point between going to bed, and waking up. Antiemetic therapy
      (metoclopramide or ondansetron) will be commenced with the first dose of Exenatide. In
      patients receiving tPA, Exenatide will be given alongside, or as soon as possible, following
      tPA administration (within 60 minutes). Diabetic patients already on oral agents and/or
      insulin may continue these (as per standard practice) in addition to Exenatide. Continuous
      glucose monitors (CGMs) will track the intra-day dynamic variability of glucose in acute
      stroke.

      Translation: TEXAIS is a simple, practical, study that can enrol all patients with ischaemic
      stroke, regardless of admission blood glucose level, regardless of stroke severity, with no
      target glucose level, and with low risk of hypoglycaemia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: improved neurological outcome
time frame: 7 days
description: Treatment with short acting Exenatide (Byetta) in patients with acute ischaemic stroke is hypothesised to improve neurological outcome as measured by ≥8 point improvement in the National Institutes of Health Stroke Scale (NIHSS) stroke disability score (or NIHSS 0-1) at 7 days
measure: post stroke hyperglycaemia
time frame: 90 days
description: reduce the occurrence of post stroke hyperglycaemia (>7mmol/l).
measure: Modified Rankin Scale
time frame: 90 days
description: improve Modified Rankin Scale (mRS) at 90 days
measure: NIHSS
time frame: 90 days
description: improve NIHSS at 90 days
arm group label: Active
arm group type: Experimental
description: Patients will receive exenatide injections
arm group label: Standard Care
arm group type: No Intervention
description: Standard care for stroke as per hospital protocol
intervention type: Drug
intervention name: Exenatide Injection
description: 5μg subcutaneously twice daily for five days, commencing within 9 hours of symptom onset
arm group label: Active
other name: Byetta
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Bladin
role: Principal Investigator
affiliation: The Florey Institute of Neuroscience & Mental Health Melbourne Brain Centre
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Finland
country: New Zealand
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Exenatide
sharing ipd: No