<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/NCT03785067</url>
  </required_header>
  <id_info>
    <org_study_id>TRIDENT COG</org_study_id>
    <nct_id>NCT03785067</nct_id>
  </id_info>
  <brief_title>Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study</brief_title>
  <acronym>TRIDENT COG</acronym>
  <official_title>Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive 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>
      A Sub-Study of an investigator initiated and conducted, multicentre, international,&#xD;
      double-blinded, placebo-controlled, parallel-group, randomised controlled trial (TRIDENT) to&#xD;
      determine the effect of more intensive long-term blood pressure control, provided by a fixed&#xD;
      low-dose combination blood pressure lowering pill (&quot;Triple Pill&quot;) strategy on top of standard&#xD;
      of care, for slowing memory decline as measured by Cambridge Neuropsychological Test&#xD;
      Automated Battery (CANTAB), in patients with a history of acute stroke due to intracerebral&#xD;
      haemorrhage (ICH).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive decline and dementia in ICH is high due to the common underlying vasculopathy of&#xD;
      cerebral small vessel disease (CSVD). However, in general, detailed cognitive outcomes in ICH&#xD;
      have been neglected, possibly due to the high mortality rate of ICH (up to 60% within the&#xD;
      first year).&#xD;
&#xD;
      Blood pressure (BP) management in those with ICH has been suboptimal. Most hypertensive&#xD;
      patients need more than two medications. Combination therapy may improve adherence and BP&#xD;
      reduction and reduce cardiovascular (CV) event rates. In the main TRIDENT study, it is&#xD;
      hypothesised that a fixed low-dose triple combination BP-lowering agent, termed the 'Triple&#xD;
      Pill' will prevent recurrent stroke. The Triple Pill is composed of a single capsule&#xD;
      containing either a combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25&#xD;
      mg, or placebo.&#xD;
&#xD;
      In addition to achieving optimal BP control, the Triple Pill also has the capacity to slow&#xD;
      cognitive decline and dementia in ICH survivors. Research shows that elevated BP is&#xD;
      associated with Alzheimer's disease and vascular dementia, even after accounting for prior&#xD;
      stroke or transient ischaemic attack, and large scale prospective studies have shown a 50%&#xD;
      reduction in dementia when BP is managed appropriately&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Contractual and financial issues.&#xD;
  </why_stopped>
  <start_date type="Actual">February 27, 2020</start_date>
  <completion_date type="Actual">February 3, 2021</completion_date>
  <primary_completion_date type="Actual">February 3, 2021</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>Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial.&#xD;
Sub-Study: Multicentre, international, single-arm trial</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Main Study: Participants are double-blinded. Sub-Study: No blinding to neuropsychological assessments</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest</measure>
    <time_frame>Baseline, 18 and 36 months</time_frame>
    <description>Raw scores and z-scores will be used. Change scores on the CANTAB PAL will be computed between baseline, 18 and 36 months (primary endpoint).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)</measure>
    <time_frame>Baseline, 18 and 36 months</time_frame>
    <description>Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change scores will be computed for CANTAB Multi-tasking Test (MTT)</measure>
    <time_frame>Baseline, 18 and 36 months</time_frame>
    <description>Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change scores will be computed for gold-standard neuropsychological assessments</measure>
    <time_frame>Baseline, 18 and 36 months</time_frame>
    <description>Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnosis of all-cause dementia</measure>
    <time_frame>36 months</time_frame>
    <description>Diagnosis of all-cause dementia as determined by consensus of three blinded adjudicators based on established criteria following collection of data of the 3-year study period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Cognitive Decline</condition>
  <condition>Intracerebral Hemorrhage</condition>
  <condition>Dementia, Vascular</condition>
  <condition>Cerebral Small Vessel Diseases</condition>
  <condition>Hypertension</condition>
  <condition>Stroke Hemorrhagic</condition>
  <arm_group>
    <arm_group_label>Triple Pill (Active Treatment)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Main Study: Fixed low-dose combination BP-lowering pill (&quot;Triple Pill&quot;) telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg&#xD;
Sub-Study: single-arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Main Study: Matched placebo, received via blinded study capsules&#xD;
Sub-Study: single-arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg</intervention_name>
    <description>1 capsule taken orally once daily for 36 months</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>1 capsule taken orally once daily for 36 months</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Eligible for, randomised and continuing in the TRIDENT Main Study&#xD;
&#xD;
          2. Must be able to attend the site conducting the cognitive assessments. In Sydney, this&#xD;
             will either be at the same site as where TRIDENT study is conducted or at the BMC,&#xD;
             University of Sydney, Camperdown.&#xD;
&#xD;
          3. Ability and willingness to undergo neuropsychological testing (i.e. have no major&#xD;
             visual, auditory or motor impairments)&#xD;
&#xD;
          4. Language spoken compatible with CANTAB administration (i.e. CANTAB will be&#xD;
             administered in the local language(s) of the country in question. E.g. in Australia,&#xD;
             the CANTAB will only be administered in English).&#xD;
&#xD;
          5. Provision of written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Study medication has been permanently stopped prior to or at the 6-month visit of the&#xD;
             TRIDENT main study&#xD;
&#xD;
          2. Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313&#xD;
             or higher&#xD;
&#xD;
          3. Cognitive performance indicative of dementia at 6-month TRIDENT main study visit&#xD;
             defined by Montreal Cognitive Assessment (MoCA) score less than 2414.&#xD;
&#xD;
          4. Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA&#xD;
             assessments between randomisation and the 6-month study visit in the TRIDENT main&#xD;
             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>Prof Craig Anderson</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Prof Sharon Naismith</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sydney</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>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>Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud University Medical Center</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 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 24, 2018</study_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TRIDENT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Cerebral Small Vessel Diseases</mesh_term>
    <mesh_term>Dementia, Vascular</mesh_term>
    <mesh_term>Hemorrhagic Stroke</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Cognitive Dysfunction</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>
  <!-- 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/NCT03785067
org study id: TRIDENT COG
nct id: NCT03785067
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A Sub-Study of an investigator initiated and conducted, multicentre, international,
      double-blinded, placebo-controlled, parallel-group, randomised controlled trial (TRIDENT) to
      determine the effect of more intensive long-term blood pressure control, provided by a fixed
      low-dose combination blood pressure lowering pill ("Triple Pill") strategy on top of standard
      of care, for slowing memory decline as measured by Cambridge Neuropsychological Test
      Automated Battery (CANTAB), in patients with a history of acute stroke due to intracerebral
      haemorrhage (ICH).
Cognitive decline and dementia in ICH is high due to the common underlying vasculopathy of
      cerebral small vessel disease (CSVD). However, in general, detailed cognitive outcomes in ICH
      have been neglected, possibly due to the high mortality rate of ICH (up to 60% within the
      first year).

      Blood pressure (BP) management in those with ICH has been suboptimal. Most hypertensive
      patients need more than two medications. Combination therapy may improve adherence and BP
      reduction and reduce cardiovascular (CV) event rates. In the main TRIDENT study, it is
      hypothesised that a fixed low-dose triple combination BP-lowering agent, termed the 'Triple
      Pill' will prevent recurrent stroke. The Triple Pill is composed of a single capsule
      containing either a combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25
      mg, or placebo.

      In addition to achieving optimal BP control, the Triple Pill also has the capacity to slow
      cognitive decline and dementia in ICH survivors. Research shows that elevated BP is
      associated with Alzheimer's disease and vascular dementia, even after accounting for prior
      stroke or transient ischaemic attack, and large scale prospective studies have shown a 50%
      reduction in dementia when BP is managed appropriately
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial.
Sub-Study: Multicentre, international, single-arm trial
primary purpose: Screening
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Main Study: Participants are double-blinded. Sub-Study: No blinding to neuropsychological assessments
measure: Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest
time frame: Baseline, 18 and 36 months
description: Raw scores and z-scores will be used. Change scores on the CANTAB PAL will be computed between baseline, 18 and 36 months (primary endpoint).
measure: Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)
time frame: Baseline, 18 and 36 months
description: Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months
measure: Change scores will be computed for CANTAB Multi-tasking Test (MTT)
time frame: Baseline, 18 and 36 months
description: Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months
measure: Change scores will be computed for gold-standard neuropsychological assessments
time frame: Baseline, 18 and 36 months
description: Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months
measure: Diagnosis of all-cause dementia
time frame: 36 months
description: Diagnosis of all-cause dementia as determined by consensus of three blinded adjudicators based on established criteria following collection of data of the 3-year study period
arm group label: Triple Pill (Active Treatment)
arm group type: Experimental
description: Main Study: Fixed low-dose combination BP-lowering pill ("Triple Pill") telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg
Sub-Study: single-arm
arm group label: Placebo
arm group type: Placebo Comparator
description: Main Study: Matched placebo, received via blinded study capsules
Sub-Study: single-arm
intervention type: Drug
intervention name: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg
description: 1 capsule taken orally once daily for 36 months
arm group label: Triple Pill (Active Treatment)
other name: Triple Pill
intervention type: Drug
intervention name: Placebo oral capsule
description: 1 capsule taken orally once daily for 36 months
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Prof Craig Anderson
role: Principal Investigator
affiliation: The George Institute
last name: Prof Sharon Naismith
role: Principal Investigator
affiliation: University of Sydney
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Netherlands
responsible party type: Sponsor
mesh term: Cerebral Hemorrhage
mesh term: Cerebral Small Vessel Diseases
mesh term: Dementia, Vascular
mesh term: Hemorrhagic Stroke
mesh term: Hemorrhage
mesh term: Cognitive Dysfunction
mesh term: Amlodipine
mesh term: Telmisartan
mesh term: Indapamide