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

NCT03785067 | Terminated Phase 3 DMC

• 1 other identifier: TRIDENT COG
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 4

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).

Conditions

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

Keywords

TRIDENT

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline, 18 and 36 months

Secondary Outcomes (4)

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

  Baseline, 18 and 36 months

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

  Baseline, 18 and 36 months

• Change scores will be computed for gold-standard neuropsychological assessments

  Baseline, 18 and 36 months

• Diagnosis of all-cause dementia

  36 months

Study Arms (2)

Triple Pill (Active Treatment)

EXPERIMENTAL

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

Drug: telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg DRUG

1 capsule taken orally once daily for 36 months

Also known as: Triple Pill

Triple Pill (Active Treatment)

Placebo oral capsule DRUG

1 capsule taken orally once daily for 36 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Institute: lead
• University of Sydney: collaborator

Study Sites (4)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Radboud University Medical Center

Nijmegen, 6525 GC, Netherlands

Location

MeSH Terms

Conditions

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

Interventions

Telmisartan; Amlodipine; Indapamide

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Dementia; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Stroke

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles

Study Officials

• Prof Craig Anderson

  The George Institute

  PRINCIPAL INVESTIGATOR

• Prof Sharon Naismith

  University of Sydney

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Main Study: Participants are double-blinded. Sub-Study: No blinding to neuropsychological assessments
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 24, 2018
• Study Start: February 27, 2020
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

AU (3); NL (1)