Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial Magnetic Resonance Imaging Sub-study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) MRI Sub-study

Conditions
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Stroke, Cerebral Small Vessel Diseases, Intracerebral Hemorrhage, Vascular Dementia, Hypertension

Intervention / Treatment
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* Drug: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for, randomised and continuing in TRIDENT Main Study No contraindications to MRI scan of the brain Provide informed consent for the MRI Sub-Study Exclusion Criteria: Any MRI contraindications (e.g. metallic implants, claustrophobia, etc.) 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triple Pill (Active Treatment)<br>telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg; | Drug: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg<br>* low-dose combination therapy<br>* Other names: Triple Pill;|
| Placebo Comparator: Placebo<br>received via blinded study oral capsules | Drug: Placebo oral capsule<br>* matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in T2 FLAIR white matter hyperintensities (WMH) volume |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1. |  | 36 months | 
| Substructure change - cortical grey matter | expected range: >400,000 and <800,000mm3 Relevant Sequence: 3D-T1 | 36 months | 
| Substructure change - white matter | expected range: >400,000 and <900,000mm3 Relevant Sequence: 3D-T1 | 36 months | 
| Substructure change - cerebrospinal fluid (CSF) | volume change measured Relevant Sequence: 3D-T1 | 36 months | 
| Change in number of cerebral microbleeds (CMBs) |  | 36 months |