Cognitive DeclinePhase 3TRIDENT COGNCT03785067
Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
A Phase 3 study testing telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg in people with Cognitive Decline and Intracerebral Hemorrhage, run by The George Institute at 4 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cognitive Decline, Intracerebral Hemorrhage, Dementia, Vascular
- What is being tested?
- telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 27 Feb 2020to 3 Feb 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible for, randomised and continuing in the TRIDENT Main Study
- Must be able to attend the site conducting the cognitive assessments. In Sydney, this will either be at the same site as where TRIDENT study is conducted or at the BMC, University of Sydney, Camperdown.
- Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)
- Language spoken compatible with CANTAB administration (i.e. CANTAB will be administered in the local language(s) of the country in question. E.g. in Australia, the CANTAB will only be administered in English).
- Provision of written informed consent
Who cannot join
- Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study
- Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher
- Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.
- Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA assessments between randomisation and the 6-month study visit in the TRIDENT main study
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Australia3 sites
Liverpool Hospital
Liverpool, New South Wales, 2170
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
About this study
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).
Read the detailed description
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
- Conditions
- Cognitive Decline, Intracerebral Hemorrhage, Dementia, Vascular, Cerebral Small Vessel Diseases, Hypertension, Stroke Hemorrhagic
- Being tested
- telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg, Placebo oral capsule
- Keywords
- TRIDENT
- Medical subject headings
- Cognitive Dysfunction, Cerebral Hemorrhage, Dementia, Vascular, Cerebral Small Vessel Diseases, Hypertension, Hemorrhagic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mgDrug
Also called Triple Pill
1 capsule taken orally once daily for 36 months
Placebo oral capsuleDrug
1 capsule taken orally once daily for 36 months
| Study group | Role | What they receive |
|---|---|---|
| Triple Pill (Active Treatment) | Experimental | Main Study: Fixed low-dose combination BP-lowering pill ("Triple Pill") telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg
Sub-Study: single-arm Receives: Drug: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg |
| Placebo | Placebo comparator | Main Study: Matched placebo, received via blinded study capsules
Sub-Study: single-arm Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest
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).
Measured: Baseline, 18 and 36 months
Secondary outcomes (4)
Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)
Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months
Measured: Baseline, 18 and 36 months
Change scores will be computed for CANTAB Multi-tasking Test (MTT)
Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months
Measured: Baseline, 18 and 36 months
Change scores will be computed for gold-standard neuropsychological assessments
Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months
Measured: Baseline, 18 and 36 months
Diagnosis of all-cause dementia
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
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2018
- Study start27 Feb 2020
- Primary completion3 Feb 2021
- Study completion3 Feb 2021
Why it stopped: Contractual and financial issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial. Sub-Study: Multicentre, international, single-arm trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sydney
- Responsible party
- Sponsor
- Investigators
- Prof Craig Anderson, Principal investigator, The George InstituteProf Sharon Naismith, Principal investigator, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03785067
- Sponsor's protocol ID
- TRIDENT COG
- Acronym
- TRIDENT COG
- Status last verified
- Mar 2021
- First submitted
- 6 Dec 2018
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
- ClinicalTrials.gov ID
- NCT03785067
- Acronym / sponsor ID
- TRIDENT COG / TRIDENT COG
- Conditions
- Cognitive Decline, Intracerebral Hemorrhage, Dementia, Vascular, Cerebral Small Vessel Diseases, Hypertension, Stroke Hemorrhagic
- Keywords
- TRIDENT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Contractual and financial issues.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- The George InstituteUniversity, hospital or other
- Collaborators
- University of Sydney
- Study start
- 27 Feb 2020 (actual)
- Primary completion
- 3 Feb 2021 (actual)
- Study completion
- 3 Feb 2021 (actual)
- First posted
- 24 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial. Sub-Study: Multicentre, international, single-arm trial
| Arm | Type | Receives |
|---|---|---|
| Triple Pill (Active Treatment) | Experimental | Drug: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mgMain Study: Fixed low-dose combination BP-lowering pill ("Triple Pill") telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg Sub-Study: single-arm |
| Placebo | Placebo comparator | Drug: Placebo oral capsuleMain Study: Matched placebo, received via blinded study capsules Sub-Study: single-arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Eligible for, randomised and continuing in the TRIDENT Main Study
- Must be able to attend the site conducting the cognitive assessments. In Sydney, this will either be at the same site as where TRIDENT study is conducted or at the BMC, University of Sydney, Camperdown.
- Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)
- Language spoken compatible with CANTAB administration (i.e. CANTAB will be administered in the local language(s) of the country in question. E.g. in Australia, the CANTAB will only be administered in English).
- Provision of written informed consent
Key exclusion criteria (4 listed)
- Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study
- Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher
- Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.
- Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA assessments between randomisation and the 6-month study visit in the TRIDENT main study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mgAlso: Triple Pill1 capsule taken orally once daily for 36 months | Drug | Triple Pill (Active Treatment) |
| Placebo oral capsule1 capsule taken orally once daily for 36 months | Drug | Placebo |
Primary outcome
Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest
Time frame: Baseline, 18 and 36 months
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).
4 secondary outcomes
Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)
Time frame: Baseline, 18 and 36 months
Change scores will be computed for CANTAB Multi-tasking Test (MTT)
Time frame: Baseline, 18 and 36 months
Change scores will be computed for gold-standard neuropsychological assessments
Time frame: Baseline, 18 and 36 months
Diagnosis of all-cause dementia
Time frame: 36 months
Results and safety
The study was stopped early (reason given: Contractual and financial issues.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof Craig Anderson principal investigator
The George Institute
Prof Sharon Naismith principal investigator
University of Sydney
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg in people with Cognitive Decline and Intracerebral Hemorrhage, run by The George Institute at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Contractual and financial issues.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest (time frame: Baseline, 18 and 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.