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Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02699645
Recruitment Status : Recruiting
First Posted : March 4, 2016
Last Update Posted : August 31, 2021
Sponsor:
Collaborator:
The University of New South Wales
Information provided by (Responsible Party):
The George Institute

Study Description
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Brief Summary:
An investigator initiated and conducted, multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial to determine the effect of more intensive blood pressure control provided by a fixed low-dose combination blood pressure lowering pill ("Triple Pill") strategy on top of standard of care, on time to first occurrence of recurrent stroke in patients with a history of stroke due to intracerebral haemorrhage.

Condition or disease Intervention/treatment Phase
Intracerebral Haemorrhage (ICH) Hypertension Drug: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg Drug: Placebo Phase 3

Detailed Description:

Intracerebral haemorrhage (ICH) is the most serious and least treatable form of stroke, accounting for at least 10% of the 20 million new strokes that occur globally each year. Survivors of ICH are at high risk of recurrent ICH and other serious cardiovascular events.

While there is strong evidence that this risk can be reduced by lowering the blood pressure (BP) of patients after ICH, many patients with ICH do not receive BP-lowering treatment long-term unless BP levels are particularly high, and many do not receive BP combination therapy.

The aim of this study is to assess the safety and efficacy of a combination of fixed low-dose generic BP lowering agents, as a "Triple Pill" strategy on top of standard of care for the prevention of recurrent stroke in patients with a history of ICH and high normal or low grade hypertension. The study is a large-scale, international, double-blind, placebo-controlled, randomised controlled trial.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Substudies: MRI, Cognitive
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Triple Pill (active treatment)
telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;
 Drug: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg
1 capsule taken orally once daily for average of 72 months
Other Name: Triple Pill
Placebo Comparator: Placebo
received via blinded study capsules
 Drug: Placebo
1 capsule taken orally once daily for average of 72 months


Outcome Measures
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Primary Outcome Measures :
  1. Recurrent Stroke [ Time Frame: Average of 6 years ]
    Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.


Secondary Outcome Measures :
  1. Recurrent ICH [ Time Frame: Average of 6 years ]
    Time to first occurrence of recurrent ICH

  2. Ischaemic Stroke [ Time Frame: Average of 6 years ]
    Time to first occurrence of ischaemic stroke

  3. Fatal or disabling stroke [ Time Frame: Average of 6 years ]
    Time to first occurrence of fatal or disabling stroke

  4. Mortality [ Time Frame: Average of 6 years ]
    Mortality

  5. MACE [ Time Frame: Average of 6 years ]
    Major adverse cardiovascular events - CV death, non-fatal MI or non-fatal stroke

  6. Physical function [ Time Frame: Average of 6 years ]
    Physical function as assessed by smRS

  7. Change in SBP [ Time Frame: Average of 6 years ]
    Change in SBP

  8. HRQoL according to the EQ-5D-3L [ Time Frame: Average of 6 years ]
    Health-related quality of life according to the European Quality of Life 5-Dimensional Assessment, 3-Level version

  9. Cognitive Impairment [ Time Frame: Average of 6 years ]
    Overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA)

  10. Cognitive Impairment Supplement [ Time Frame: Average of 6 years ]
    Overall defined by standard cut-points with Brief Memory and Executive Test (BMET)

  11. Medication Adherence [ Time Frame: Average of 6 years ]
    Self-reported measures, Pill counts


Eligibility Criteria
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Information from the National Library of Medicine

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

Inclusion Criteria:

  • Adults (≥18 years) with a history of up to 12 months after symptom onset of primary ICH that is confirmed by imaging (copy of the brain imaging report to be uploaded to the database, labelled with participant identification (ID) and with personal identifiers removed)
  • Clinically stable, as judged by investigator
  • Average of two resting SBP levels measured 5 minutes apart in the range 130-160mmHg recorded in a seated position (National Heart Foundation of Australia Guidelines). (Patients with higher SBP can be included if considered by attending clinician that management is consistent with local standards of clinical practice)
  • Geographical proximity to the recruiting hospital and/or follow-up medical clinic site to allow ready access for in-person clinic visits during follow-up
  • No clear contraindication to any of the study treatments
  • Provision of written informed consent

Exclusion Criteria:

  • Taking an ACE-I that cannot be switched to any of the following alternatives:

    • telmisartan 20 or 40mg, amlodipine 2.5 or 5mg, indapamide 1.25mg, or
    • an equivalent class (ARB, CCB or thiazide [TZ]-like diuretic), or
    • a BB
  • Contraindication to any of the study medications, in the context of currently prescribed BP-lowering medication
  • Unable to complete the study procedures and/or follow-up
  • Females of child-bearing age and capability, who are pregnant or breast-feeding, or those of child-bearing age and capability who are not using adequate birth control
  • Significant hyperkalaemia and/or hyponatremia, in the opinion of the responsible physician
  • Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2
  • Severe hepatic impairment (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3x the upper limit of normal [ULN])
  • Any other condition that in the opinion of the responsible physician investigator renders the patient unsuitable for the study (e.g. severe disability [i.e. simplified modified Rankin Scale (smRS) of 4-5] or significant memory or behavioural disorder)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02699645


Contacts
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Contact: Grace Balicki +61 2 8052 4811 gbalicki@georgeinstitute.org.au
Contact: Ruth Freed +61 2 8052 4522 rfreed@georgeinstitute.org.au

Locations
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Sponsors and Collaborators
The George Institute
The University of New South Wales
Investigators
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Principal Investigator: Craig Anderson The George Institute
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT02699645    
Other Study ID Numbers: TRIDENT-1103886
First Posted: March 4, 2016    Key Record Dates
Last Update Posted: August 31, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 2 years after publication of main results
Access Criteria: Bone fide researchers submit protocol to the Research Office of The George Institute for Global Health

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by The George Institute:
Blood Pressure (BP)
Stroke
Additional relevant MeSH terms:
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Cerebral Hemorrhage
Hemorrhage
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System 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
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors