Clinical trial NCT03783754: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial Magnetic Resonance Imaging Sub-study
Official title: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) MRI Sub-study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke
Cerebral Small Vessel Diseases
Intracerebral Hemorrhage
Vascular Dementia
Hypertension
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: University of Sydney
First posted: 2018-12-21
Enrollment: 4
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
Primary purpose: SCREENING

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in T2 FLAIR white matter hyperintensities (WMH) volume
timeFrame: 36 months
Secondary outcomes:
measure: Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1.
timeFrame: 36 months
measure: Substructure change - cortical grey matter
timeFrame: 36 months
measure: Substructure change - white matter
timeFrame: 36 months
measure: Substructure change - cerebrospinal fluid (CSF)
timeFrame: 36 months
measure: Change in number of cerebral microbleeds (CMBs)
timeFrame: 36 months
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: The George Institute
name: Craig Anderson, Prof
role: PRINCIPAL_INVESTIGATOR
References: