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

• ClinicalTrials.gov Identifier: NCT03783754
• Recruitment Status: Terminated
• First Posted: December 21, 2018
• Last Update Posted: May 25, 2021
• Sponsor: The George Institute
• Collaborator: University of Sydney
• Information provided by (Responsible Party): The George Institute

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	Not Applicable

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 (Clinical Trial)
• 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 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: August 9, 2018
• Actual Primary Completion Date: March 21, 2021
• Actual Study Completion Date: March 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 Name: Triple Pill
Placebo Comparator: Placebo; received via blinded study oral capsules	Drug: Placebo oral capsule; matched placebo

Outcome Measures

Primary Outcome Measures :

1. Change in T2 FLAIR white matter hyperintensities (WMH) volume [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Whole brain atrophy measured by percentage brain volume change between baseline and 36 months on HIRES-T1. [ Time Frame: 36 months ]
2. Substructure change - cortical grey matter [ Time Frame: 36 months ]
   expected range: >400,000 and <800,000mm3 Relevant Sequence: 3D-T1
3. Substructure change - white matter [ Time Frame: 36 months ]
   expected range: >400,000 and <900,000mm3 Relevant Sequence: 3D-T1
4. Substructure change - cerebrospinal fluid (CSF) [ Time Frame: 36 months ]
   volume change measured Relevant Sequence: 3D-T1
5. Change in number of cerebral microbleeds (CMBs) [ Time Frame: 36 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Australia, New South Wales

Liverpool Hospital

Liverpool, New South Wales, Australia, 2170

Australia, Queensland

Sunshine Coast University Hospital

Birtinya, Queensland, Australia, 4575

Australia, Victoria

Royal Melbourne Hospital

Melbourne, Victoria, Australia, 3050

Sponsors and Collaborators

The George Institute

University of Sydney

Investigators

• Principal Investigator: Craig Anderson, Prof; The George Institute

More Information

• Responsible Party: The George Institute
• ClinicalTrials.gov Identifier: NCT03783754
• Other Study ID Numbers: TRIDENT MRI
• First Posted: December 21, 2018
• Last Update Posted: May 25, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cerebral Hemorrhage; Dementia, Vascular; Cerebral Small Vessel Diseases; Hemorrhage; Vascular Diseases; Cardiovascular Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Amlodipine; Telmisartan; Indapamide; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents