Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study

NCT ID: NCT03785067

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-27
• Study Completion Date: 2021-02-03

Brief Summary

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 blood pressure control, provided by a fixed low-dose combination blood pressure lowering pill ("Triple Pill") strategy on top of standard of care, for slowing memory decline as measured by Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with a history of acute stroke due to intracerebral haemorrhage (ICH).

Detailed Description

Cognitive decline and dementia in ICH is high due to the common underlying vasculopathy of cerebral small vessel disease (CSVD). However, in general, detailed cognitive outcomes in ICH have been neglected, possibly due to the high mortality rate of ICH (up to 60% within the first year).

Blood pressure (BP) management in those with ICH has been suboptimal. Most hypertensive patients need more than two medications. Combination therapy may improve adherence and BP reduction and reduce cardiovascular (CV) event rates. In the main TRIDENT study, it is hypothesised that a fixed low-dose triple combination BP-lowering agent, termed the 'Triple Pill' will prevent recurrent stroke. The Triple Pill is composed of a single capsule containing either a combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg, or placebo.

In addition to achieving optimal BP control, the Triple Pill also has the capacity to slow cognitive decline and dementia in ICH survivors. Research shows that elevated BP is associated with Alzheimer's disease and vascular dementia, even after accounting for prior stroke or transient ischaemic attack, and large scale prospective studies have shown a 50% reduction in dementia when BP is managed appropriately

Conditions

Cognitive Decline; Intracerebral Hemorrhage; Dementia, Vascular; Cerebral Small Vessel Diseases; Hypertension; Stroke Hemorrhagic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: QUADRUPLE

Study Groups

Triple Pill (Active Treatment)

Main Study: Fixed low-dose combination BP-lowering pill ("Triple Pill") telmisartan 20mg + amlodipine 2.5mg + indapamide 1.25mg

Sub-Study: single-arm

Group Type: EXPERIMENTAL

telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg

Intervention Type: DRUG

1 capsule taken orally once daily for 36 months

Placebo

Main Study: Matched placebo, received via blinded study capsules

Sub-Study: single-arm

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

1 capsule taken orally once daily for 36 months

Interventions

telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg

1 capsule taken orally once daily for 36 months

Intervention Type: DRUG

Placebo oral capsule

1 capsule taken orally once daily for 36 months

Intervention Type: DRUG

Other Intervention Names

Triple Pill

Eligibility Criteria

Inclusion Criteria

1. Eligible for, randomised and continuing in the TRIDENT Main Study

2. Must be able to attend the site conducting the cognitive assessments. In Sydney, this will either be at the same site as where TRIDENT study is conducted or at the BMC, University of Sydney, Camperdown.

3. Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)

4. Language spoken compatible with CANTAB administration (i.e. CANTAB will be administered in the local language(s) of the country in question. E.g. in Australia, the CANTAB will only be administered in English).

5. Provision of written informed consent

Exclusion Criteria

1. Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study

2. Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher

3. Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.

4. Evidence of rapid deterioration suggestive of dementia by decline of 3 points in MoCA assessments between randomisation and the 6-month study visit in the TRIDENT main study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sydney

OTHER

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof Craig Anderson

Role: PRINCIPAL_INVESTIGATOR

The George Institute

Prof Sharon Naismith

Role: PRINCIPAL_INVESTIGATOR

University of Sydney

Locations

Liverpool Hospital

Liverpool, New South Wales, Australia

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Radboud University Medical Center

Nijmegen, , Netherlands

Countries

Australia; Netherlands

Other Identifiers

TRIDENT COG

Identifier Type: -

Identifier Source: org_study_id