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

Not Applicable

Terminated

• Conditions: Intracerebral Hemorrhage; Stroke; Cerebral Small Vessel Diseases; Vascular Dementia; Hypertension
• Interventions: Drug: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg; Drug: Placebo oral capsule

• Registration Number: NCT03783754
• Lead Sponsor: The George Institute

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.

Study Timeline

• Study Start: 2018-08-09
• Study First Submitted: 2018-12-06
• Study First Submitted QC: 2018-12-19
• Study First Posted: 2018-12-21
• Primary Completion: 2021-03-21
• Study Completion: 2021-03-21
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-24
• Last Update Posted: 2021-05-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Triple Pill (Active Treatment)	telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg	telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;
Placebo	Placebo oral capsule	received via blinded study oral capsules

Primary Outcome Measures

Name	Time	Method
Change in T2 FLAIR white matter hyperintensities (WMH) volume	36 months

Secondary Outcome Measures

Name	Time	Method
Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1.	36 months
Substructure change - cerebrospinal fluid (CSF)	36 months	volume change measured Relevant Sequence: 3D-T1
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
Change in number of cerebral microbleeds (CMBs)	36 months

Trial Locations

Locations (3)

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Queensland, Australia