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

Primary Purpose

Cognitive Decline, Intracerebral Hemorrhage, Dementia, Vascular

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg

Placebo oral capsule

About this trial

This is an interventional screening trial for Cognitive Decline focused on measuring TRIDENT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Eligible for, randomised and continuing in the TRIDENT Main Study
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.
Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments)
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).
Provision of written informed consent

Exclusion Criteria:

Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study
Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher
Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414.
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

Sites / Locations

Liverpool Hospital
Royal Prince Alfred Hospital
Royal Melbourne Hospital
Radboud University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Triple Pill (Active Treatment)

Placebo

Arm Description

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

Main Study: Matched placebo, received via blinded study capsules Sub-Study: single-arm

Outcomes

Primary Outcome Measures

Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest

Raw scores and z-scores will be used. Change scores on the CANTAB PAL will be computed between baseline, 18 and 36 months (primary endpoint).

Secondary Outcome Measures

Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)

Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months

Change scores will be computed for CANTAB Multi-tasking Test (MTT)

Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months

Change scores will be computed for gold-standard neuropsychological assessments

Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months

Diagnosis of all-cause dementia

Diagnosis of all-cause dementia as determined by consensus of three blinded adjudicators based on established criteria following collection of data of the 3-year study period

Full Information

NCT ID

NCT03785067

First Posted

December 6, 2018

Last Updated

March 29, 2021

Sponsor

The George Institute

Collaborators

University of Sydney

1. Study Identification

Unique Protocol Identification Number

NCT03785067

Brief Title

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

Acronym

TRIDENT COG

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Terminated

Why Stopped

Contractual and financial issues.

Study Start Date

February 27, 2020 (Actual)

Primary Completion Date

February 3, 2021 (Actual)

Study Completion Date

February 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The George Institute

Collaborators

University of Sydney

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

TRIDENT

7. Study Design

Primary Purpose

Screening

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Main Study: Multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial. Sub-Study: Multicentre, international, single-arm trial

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Main Study: Participants are double-blinded. Sub-Study: No blinding to neuropsychological assessments

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Triple Pill (Active Treatment)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Main Study: Matched placebo, received via blinded study capsules Sub-Study: single-arm

Intervention Type

Drug

Intervention Name(s)

telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg

Other Intervention Name(s)

Triple Pill

Intervention Description

1 capsule taken orally once daily for 36 months

Intervention Type

Drug

Intervention Name(s)

Placebo oral capsule

Intervention Description

1 capsule taken orally once daily for 36 months

Primary Outcome Measure Information:

Title

Memory as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) subtest

Description

Raw scores and z-scores will be used. Change scores on the CANTAB PAL will be computed between baseline, 18 and 36 months (primary endpoint).

Time Frame

Baseline, 18 and 36 months

Secondary Outcome Measure Information:

Title

Change scores will be computed for CANTAB Rapid Visual Information Processing (RVP)

Description

Change scores will be computed for CANTAB RVP between baseline, 18 and 36 months

Time Frame

Baseline, 18 and 36 months

Title

Change scores will be computed for CANTAB Multi-tasking Test (MTT)

Description

Change scores will be computed for CANTAB MTT between baseline, 18 and 36 months

Time Frame

Baseline, 18 and 36 months

Title

Change scores will be computed for gold-standard neuropsychological assessments

Description

Change scores will be computed for gold-standard neuropsychological assessment between baseline, 18 and 36 months

Time Frame

Baseline, 18 and 36 months

Title

Diagnosis of all-cause dementia

Description

Diagnosis of all-cause dementia as determined by consensus of three blinded adjudicators based on established criteria following collection of data of the 3-year study period

Time Frame

36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Eligible for, randomised and continuing in the TRIDENT Main Study 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. Ability and willingness to undergo neuropsychological testing (i.e. have no major visual, auditory or motor impairments) 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). Provision of written informed consent Exclusion Criteria: Study medication has been permanently stopped prior to or at the 6-month visit of the TRIDENT main study Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) score of 3.313 or higher Cognitive performance indicative of dementia at 6-month TRIDENT main study visit defined by Montreal Cognitive Assessment (MoCA) score less than 2414. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Prof Craig Anderson

Organizational Affiliation

The George Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Prof Sharon Naismith

Organizational Affiliation

University of Sydney

Official's Role

Principal Investigator

Facility Information:

Facility Name

Liverpool Hospital

City

Liverpool

State/Province

New South Wales

ZIP/Postal Code

2170

Country

Australia

Facility Name

Royal Prince Alfred Hospital

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

Royal Melbourne Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3050

Country

Australia

Facility Name

Radboud University Medical Center

City

Nijmegen

ZIP/Postal Code

6525 GC

Country

Netherlands

12. IPD Sharing Statement

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

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