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Trial registered on ANZCTR


Registration number
ACTRN12618001977268
Ethics application status
Approved
Date submitted
9/10/2018
Date registered
7/12/2018
Date last updated
27/06/2019
Date data sharing statement initially provided
7/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Magnetic Resonance Imaging (MRI) Sub-study: Effect of intensive blood pressure lowering treatment provided by a Triple Pill strategy on chronic markers of cerebral small vessel disease in patients with a history of acute stroke due to intracerebral haemorrhage, as assessed by Magnetic Resonance Imaging.
Scientific title
A sub-study of an investigator initiated and conducted, multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial (TRIDENT) to determine the effect of more intensive long-term intensive blood pressure control, provided by a fixed low-dose combination blood pressure lowering pill (“Triple Pill”) strategy on top of standard of care, on chronic markers of cerebral small vessel disease in patients with a history of acute stroke due to intracerebral haemorrhage (ICH), as assessed by Magnetic Resonance Imaging (MRI).
Secondary ID [1] 295590 0
None
Universal Trial Number (UTN)
Trial acronym
TRIDENT MRI
Linked study record
This study is a sub-study of ACTRN12616000327482 Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT). Participants must be enrolled and participating in the TRIDENT main study to be eligible for this study.

Health condition
Health condition(s) or problem(s) studied:
Stroke caused by Intracerebral Haemorrhage (ICH) 308933 0
Hypertension 309344 0
Cerebral Small Vessel Disease 309345 0
Condition category
Condition code
Stroke 307834 307834 0 0
Haemorrhagic
Cardiovascular 307835 307835 0 0
Hypertension
Neurological 308208 308208 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
TRIDENT:
Triple Pill (active treatment) - telmisartan 20mg, amlodipine 2.5mg and indapamide 1.25mg; taken orally, once daily for 36 months. Medication adherence and accountability is monitored through self-reports of doses missed and pill counts at every visit until end of treatment (Visits 3-9).

MRI Sub-study:
Participants at participating sites with MRI scanners capable of the tests required will be considered to be eligible for the study if they meet all inclusion criteria and do not meet any exclusion criteria. Those that are eligible for the sub-study will undergo MRI scans at baseline (6 weeks - 6 months post-randomisation into the main study) and at 36-month follow-up time points to analyse chronic markers of cerebral small vessel disease (CSVD) – white matter hyperintensities (WMH), cerebral microbleeds (CMB), lacunes, perivascular spaces, cerebral atrophy, and cortical superficial siderosis (CSS).
Intervention code [1] 301909 0
Diagnosis / Prognosis
Comparator / control treatment
TRIDENT: Placebo - commonly used excipients (to be determined) received via blinded study capsules
Control group
Placebo

Outcomes
Primary outcome [1] 306810 0
Change in T2 FLAIR WMH volume between baseline (6 weeks to 6 months post-randomisation) and 36 months.
Timepoint [1] 306810 0
36 months
Secondary outcome [1] 349711 0
Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1.
Timepoint [1] 349711 0
36 months
Secondary outcome [2] 349712 0
Composite substructure change (cortical grey matter, white matter and CSF) between baseline and 36 months.
Timepoint [2] 349712 0
36 months
Secondary outcome [3] 349713 0
Change in number of CMBs between baseline and 36 months on Susceptibility Weighted Imaging (SWI).
Timepoint [3] 349713 0
36 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A sample size of 750 patients will provide 90% power (alpha=0.05) to detect more than a 20% difference between the two randomised groups in the primary outcome measure, assuming equal participation between the two treatment groups. A 20% dropout per year was estimated for a 3-year follow-up.

The intention-to-treat principle will be applied in the analysis. The primary endpoint of proportion of white matter lesions (WML) will be analysed by logistic regression models.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 11474 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 14106 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 23495 0
2170 - Liverpool
Recruitment postcode(s) [2] 26899 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 300170 0
Government body
Name [1] 300170 0
National Health & Medical Research Council of Australia
Address [1] 300170 0
Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country [1] 300170 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 5, 1 King Street, Newtown NSW, 2042
Country
Australia
Secondary sponsor category [1] 299578 0
University
Name [1] 299578 0
Sydney Neuroimaging Analysis Centre, University of Sydney
Address [1] 299578 0
4/94 Mallett St, Camperdown NSW 2050
Country [1] 299578 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301002 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 301002 0
Royal Prince Alfred Hospital
Missenden Road, CAMPERDOWN, NSW, 2050
Ethics committee country [1] 301002 0
Australia
Date submitted for ethics approval [1] 301002 0
21/10/2017
Approval date [1] 301002 0
02/11/2017
Ethics approval number [1] 301002 0
HERC\EXECOR\17-11

Summary
Brief summary
The Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial or ‘TRIDENT’, is investigating the effectiveness of more intensive blood pressure (BP)-lowering treatment to prevent recurrent stroke. The intensive BP-lowering treatment in TRIDENT is a single capsule containing three low-dose BP-lowering medications or placebo. As part of the TRIDENT study, we are inviting participants to participate in the TRIDENT MRI Sub-study to assess the effectiveness of the TRIDENT study treatment on progression of cerebral small vessel disease (CSVD) as assessed by Magnetic Resonance Imaging (MRI).

Cerebral small vessel disease (CSVD) is a disease process in the brain involving small blood vessels. CSVD is common in people who have had a stroke caused by intracerebral haemorrhage (ICH) (large bleed in the brain). CSVD has been shown to be associated with dementia, cognitive decline, balance disturbances and other neurological conditions such as Parkinson’s disease.

CSVD is also known to be more common in people with high BP or hypertension. There is uncertainty however, if lowering BP slows the progression of CSVD. The purpose of this study is to measure markers of CSVD by MRI to investigate the effect of intensive BP-lowering treatment on the progression of CSVD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85558 0
Prof Craig Anderson
Address 85558 0
The George Institute for Global Health, Australia Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 85558 0
Australia
Phone 85558 0
+61 2 8052 4521
Fax 85558 0
Email 85558 0
canderson@georgeinstitute.org.au
Contact person for public queries
Name 85559 0
Ms Ruth Freed
Address 85559 0
The George Institute for Global Health, Australia Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 85559 0
Australia
Phone 85559 0
+61 2 8052 4522
Fax 85559 0
Email 85559 0
rfreed@georgeinstitute.org.au
Contact person for scientific queries
Name 85560 0
Prof Craig Anderson
Address 85560 0
The George Institute for Global Health, Australia Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 85560 0
Australia
Phone 85560 0
+61 2 8052 4521
Fax 85560 0
Email 85560 0
canderson@georgeinstitute.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
privacy laws
What supporting documents are/will be available?
No other documents available
Summary results
No Results