Cerebral Small Vessel Diseases, Hypertension, Intracerebral Hemorrhage, Stroke, Vascular Dementia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGtelmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg
low-dose combination therapy
DRUGPlacebo oral capsule
matched placebo
Sponsors
University of Sydney
The George Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Eligible for, randomised and continuing in TRIDENT Main Study 2. No contraindications to MRI scan of the brain 3. Provide informed consent for the MRI Sub-Study
Exclusion criteria
1. Any MRI contraindications (e.g. metallic implants, claustrophobia, etc.) 2. Less than 6 weeks or greater than 6 months post-randomisation (however, where possible the baseline MRI Sub-Study scan should be conducted as soon as possible after the qualifying ICH. e.g. if the qualifying ICH was 4 months prior to randomisation, the baseline scan should be done as close to 6 weeks post-randomisation as possible)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in T2 FLAIR white matter hyperintensities (WMH) volume | 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1. | 36 months | — |
| Substructure change - cortical grey matter | 36 months | expected range: \>400,000 and \<800,000mm3 Relevant Sequence: 3D-T1 |
| Substructure change - white matter | 36 months | expected range: \>400,000 and \<900,000mm3 Relevant Sequence: 3D-T1 |
| Substructure change - cerebrospinal fluid (CSF) | 36 months | volume change measured Relevant Sequence: 3D-T1 |
| Change in number of cerebral microbleeds (CMBs) | 36 months | — |
Countries
Australia
Outcome results
None listed