Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study: Effectiveness of intensive long-term blood pressure lowering treatment, provided by a Triple Pill strategy, 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.

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).

Status

Terminated

Phases

Unknown

Study type

Observational

Source

ANZCTR

Registry ID

ACTRN12618001677291

Acronym

TRIDENT Cognitive

Enrollment

Registered

2018-10-11

Start date

2020-02-21

Completion date

2020-02-21

Last updated

2021-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial or ‘TRIDENT’, is investigating the effectiveness of more intensive blood pressure-lowering treatment to prevent recurrent stroke. As part of the TRIDENT study, we are inviting participants to the TRIDENT Cognitive Sub-study to assess the effectiveness of the TRIDENT blood pressure-lowering study treatment on cognition as assessed by neuropsychological tests. ‘Cognition’ is a term referring to memory and other thinking skills. These processes include speed of thinking, finding words, visual skills and problem-solving. Neuropsychological tests, also referred to as ‘cognitive assessments’ assess these mental processes. Cerebral small vessel disease (CSVD) is a disease process in the brain involving small blood vessels. CSVD is common in people who have had a stroke caused by intracerebral haemorrhage (ICH) (large bleed in the brain). CSVD has been shown to be associated with dementia, memory problems, balance disturbances and other neurological conditions such as Parkinson’s disease. CSVD is also known to be more common in people with high blood pressure or hypertension. There is uncertainty, however, if lowering blood pressure slows the progression of cognitive decline associated with CSVD. The purpose of this study is to investigate the effect of intensive blood pressure-lowering treatment on cognitive decline measured by specific neuropsychological tests.

Interventions

TRIDENT: Triple Pill (active treatment) - telmisartan 20mg, amlodipine 2.5mg and indapamide 1.25mg; taken orally, once daily for 36 months. Medication adherence and accountability is monitored through self-reports of doses missed and pill counts at every visit until end of treatment (Visits 3-9). Cognitive Sub-study: All participants who are involved in the start-up phase of the main study will be invited to participate in the Cognitive Sub-study. Consenting participants will undergo cognitive assessments using CANTAB, a well-validated cognitive assessment battery administered via iPad. This involves three computer-based assessment tasks: • Paired Associates Learning (PAL) • Rapid Visual Information Processing (RVP) • Multitask Test (MTT) Assessments will be carried out at baseline (6 months post-randomisation period), 18 months and 36 months. Participants recruited from Sydney-based TRIDENT sites will also be offered the opportunity to undergo additional cognitive assessments at the BMC, University of Sydney using a battery of gold standard, paper-and-pencil neuropsychological tests at baseline (6 months post-randomisation), 18 months and 36 months. These tests may also be conducted at other TRIDENT centres with involvement of a trained neuropsychologist. The gold-standard assessments include: • Trails A – assessing processing speed • Trails B – assessing executive functioning • Rey Auditory Verbal Learning Test (RAVLT) – assessing verbal learning and memory • Delis-Kaplan Executive Functioning System (D-KEFS) “Stroop” Colour-Word Interference Test – assessing executive functioning • Controlled Oral Word Association Test (COWAT) – assessing language • Test of Premorbid Functioning (TOPF) – assessing pre-morbid intelligence for descriptive purposes

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

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 3.3 or higher 3. Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 24. 4. Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA assessments between randomisation and the 6-month study visits in the TRIDENT main study

Outcome results