Clinical trial NCT03785067: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
Official title: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cognitive Decline
Intracerebral Hemorrhage
Dementia, Vascular
Cerebral Small Vessel Diseases
Hypertension
Stroke Hemorrhagic
Keywords: TRIDENT
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: University of Sydney
First posted: 2018-12-24
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief 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 ("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

Eligibility criteria: Inclusion Criteria:

1. Eligible for, randomised and continuing in the TRIDENT Main Study
2. 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.
3. Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)
4. 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).
5. Provision of written informed consent

Exclusion Criteria:

1. Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study
2. Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher
3. Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.
4. 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

Primary outcomes:
measure: Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest
timeFrame: Baseline, 18 and 36 months
Secondary outcomes:
measure: Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)
timeFrame: Baseline, 18 and 36 months
measure: Change scores will be computed for CANTAB Multi-tasking Test (MTT)
timeFrame: Baseline, 18 and 36 months
measure: Change scores will be computed for gold-standard neuropsychological assessments
timeFrame: Baseline, 18 and 36 months
measure: Diagnosis of all-cause dementia
timeFrame: 36 months
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: The George Institute
name: Prof Craig Anderson
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Prof Sharon Naismith
role: PRINCIPAL_INVESTIGATOR
References: