<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/NCT03783754</url>
  </required_header>
  <id_info>
    <org_study_id>TRIDENT MRI</org_study_id>
    <nct_id>NCT03783754</nct_id>
  </id_info>
  <brief_title>Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial Magnetic Resonance Imaging Sub-study</brief_title>
  <acronym>TRIDENT-MRI</acronym>
  <official_title>Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) MRI Sub-study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The George Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sydney</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The George Institute</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>
      TRIDENT Main Study:&#xD;
&#xD;
      TRIDENT is a multicentre, international, double-blinded, placebo-controlled, parallel-group,&#xD;
      randomised controlled trial of a fixed low-dose combination BP-lowering pill (&quot;Triple Pill&quot;)&#xD;
      strategy on top of standard of care, in patients with a history of acute intracerebral&#xD;
      haemorrhage (ICH) and systolic blood pressure (SBP) levels defined as 'high normal to&#xD;
      borderline high', and on either minimal or no BP-lowering treatment according to current&#xD;
      guidelines.&#xD;
&#xD;
      MRI Sub-Study Centres capable of specific MRI of the brain sequences will be identified. The&#xD;
      patients in the TRIDENT main study who are identified to be eligible for the MRI Sub-Study&#xD;
      will undergo MRI scans at baseline (6 weeks to 6 months post-randomisation) and at 36-month&#xD;
      follow-up time points. All data collected will be analysed centrally at the Brain and Mind&#xD;
      Centre (BMC) in Sydney, Australia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intracerebral haemorrhage (ICH) is the most serious type of stroke, accounting for 10% of&#xD;
      stroke in high-income countries and up to 50% in low-to-middle income countries, especially&#xD;
      in Asia where hypertension is common. ICH in the context of hypertension is often a&#xD;
      manifestation of underlying cerebral small vessel disease (CSVD).&#xD;
&#xD;
      In summary, there is a considerable body of evidence supporting and association of CSVD with&#xD;
      hypertension and poor outcomes, but limited evidence as to whether good BP control can modify&#xD;
      the natural history of this condition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Not feasible to continue&#xD;
  </why_stopped>
  <start_date type="Actual">August 9, 2018</start_date>
  <completion_date type="Actual">March 21, 2021</completion_date>
  <primary_completion_date type="Actual">March 21, 2021</primary_completion_date>
  <phase>N/A</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>Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in T2 FLAIR white matter hyperintensities (WMH) volume</measure>
    <time_frame>36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1.</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substructure change - cortical grey matter</measure>
    <time_frame>36 months</time_frame>
    <description>expected range: &gt;400,000 and &lt;800,000mm3 Relevant Sequence: 3D-T1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substructure change - white matter</measure>
    <time_frame>36 months</time_frame>
    <description>expected range: &gt;400,000 and &lt;900,000mm3 Relevant Sequence: 3D-T1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substructure change - cerebrospinal fluid (CSF)</measure>
    <time_frame>36 months</time_frame>
    <description>volume change measured Relevant Sequence: 3D-T1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in number of cerebral microbleeds (CMBs)</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Stroke</condition>
  <condition>Cerebral Small Vessel Diseases</condition>
  <condition>Intracerebral Hemorrhage</condition>
  <condition>Vascular Dementia</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Triple Pill (Active Treatment)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>received via blinded study oral capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg</intervention_name>
    <description>low-dose combination therapy</description>
    <arm_group_label>Triple Pill (Active Treatment)</arm_group_label>
    <other_name>Triple Pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>matched placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Eligible for, randomised and continuing in TRIDENT Main Study&#xD;
&#xD;
          2. No contraindications to MRI scan of the brain&#xD;
&#xD;
          3. Provide informed consent for the MRI Sub-Study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any MRI contraindications (e.g. metallic implants, claustrophobia, etc.)&#xD;
&#xD;
          2. Less than 6 weeks or greater than 6 months post-randomisation (however, where possible&#xD;
             the baseline MRI Sub-Study scan should be conducted as soon as possible after the&#xD;
             qualifying ICH. e.g. if the qualifying ICH was 4 months prior to randomisation, the&#xD;
             baseline scan should be done as close to 6 weeks post-randomisation as possible)&#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, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute</affiliation>
  </overall_official>
  <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 Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>May 24, 2021</last_update_submitted>
  <last_update_submitted_qc>May 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2021</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>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Dementia, Vascular</mesh_term>
    <mesh_term>Cerebral Small Vessel Diseases</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amlodipine</mesh_term>
    <mesh_term>Telmisartan</mesh_term>
    <mesh_term>Indapamide</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/NCT03783754
org study id: TRIDENT MRI
nct id: NCT03783754
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
TRIDENT Main Study:

      TRIDENT is a multicentre, international, double-blinded, placebo-controlled, parallel-group,
      randomised controlled trial of a fixed low-dose combination BP-lowering pill ("Triple Pill")
      strategy on top of standard of care, in patients with a history of acute intracerebral
      haemorrhage (ICH) and systolic blood pressure (SBP) levels defined as 'high normal to
      borderline high', and on either minimal or no BP-lowering treatment according to current
      guidelines.

      MRI Sub-Study Centres capable of specific MRI of the brain sequences will be identified. The
      patients in the TRIDENT main study who are identified to be eligible for the MRI Sub-Study
      will undergo MRI scans at baseline (6 weeks to 6 months post-randomisation) and at 36-month
      follow-up time points. All data collected will be analysed centrally at the Brain and Mind
      Centre (BMC) in Sydney, Australia.
Intracerebral haemorrhage (ICH) is the most serious type of stroke, accounting for 10% of
      stroke in high-income countries and up to 50% in low-to-middle income countries, especially
      in Asia where hypertension is common. ICH in the context of hypertension is often a
      manifestation of underlying cerebral small vessel disease (CSVD).

      In summary, there is a considerable body of evidence supporting and association of CSVD with
      hypertension and poor outcomes, but limited evidence as to whether good BP control can modify
      the natural history of this condition.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial
primary purpose: Screening
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in T2 FLAIR white matter hyperintensities (WMH) volume
time frame: 36 months
measure: Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1.
time frame: 36 months
measure: Substructure change - cortical grey matter
time frame: 36 months
description: expected range: >400,000 and <800,000mm3 Relevant Sequence: 3D-T1
measure: Substructure change - white matter
time frame: 36 months
description: expected range: >400,000 and <900,000mm3 Relevant Sequence: 3D-T1
measure: Substructure change - cerebrospinal fluid (CSF)
time frame: 36 months
description: volume change measured Relevant Sequence: 3D-T1
measure: Change in number of cerebral microbleeds (CMBs)
time frame: 36 months
arm group label: Triple Pill (Active Treatment)
arm group type: Experimental
description: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;
arm group label: Placebo
arm group type: Placebo Comparator
description: received via blinded study oral capsules
intervention type: Drug
intervention name: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg
description: low-dose combination therapy
arm group label: Triple Pill (Active Treatment)
other name: Triple Pill
intervention type: Drug
intervention name: Placebo oral capsule
description: matched placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Craig Anderson, Prof
role: Principal Investigator
affiliation: The George Institute
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Cerebral Hemorrhage
mesh term: Dementia, Vascular
mesh term: Cerebral Small Vessel Diseases
mesh term: Hemorrhage
mesh term: Amlodipine
mesh term: Telmisartan
mesh term: Indapamide
sharing ipd: No