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

Sponsor

The George Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT03783754

Collaborator

University of Sydney (Other)

Enrollment

Locations

Arms

31.4

Actual Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Cerebral Small Vessel Diseases Intracerebral Hemorrhage Vascular Dementia Hypertension	Drug: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg Drug: Placebo oral capsule	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trialMain Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Aug 9, 2018

Actual Primary Completion Date :

Mar 21, 2021

Actual Study Completion Date :

Mar 21, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Triple Pill (Active Treatment)

telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;

Drug: telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg

low-dose combination therapy

Other Names:

Triple Pill

Placebo Comparator: Placebo

received via blinded study oral capsules

Drug: Placebo oral capsule

matched placebo

Outcome Measures

Primary Outcome Measures

Change in T2 FLAIR white matter hyperintensities (WMH) volume [36 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
2	Sunshine Coast University Hospital	Birtinya	Queensland	Australia	4575
3	Royal Melbourne Hospital	Melbourne	Victoria	Australia	3050