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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: The George Institute
• Collaborators: University of Sydney
• Investigators: Principal Investigator: Craig Anderson, Prof, The George Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2018
• Primary Completion (Actual): March 21, 2021
• Study Completion (Actual): March 21, 2021

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Dementia; Intracranial Arterial Diseases; Intracranial Hemorrhages; Intracranial Arteriosclerosis; Leukoencephalopathies; Hemorrhage; Cerebral Hemorrhage; Dementia, Vascular; Cerebral Small Vessel Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Telmisartan; Indapamide
• Other Study ID Numbers: TRIDENT MRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No