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

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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

Tracking Information
First Submitted Date  ICMJE March 2, 2016
First Posted Date  ICMJE March 4, 2016
Last Update Posted Date August 31, 2021
Actual Study Start Date  ICMJE September 28, 2017
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 25, 2021)
Recurrent Stroke [ Time Frame: Average of 6 years ]
Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.
Original Primary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
Recurrent stroke [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2021)
  • Recurrent ICH [ Time Frame: Average of 6 years ]
    Time to first occurrence of recurrent ICH
  • Ischaemic Stroke [ Time Frame: Average of 6 years ]
    Time to first occurrence of ischaemic stroke
  • Fatal or disabling stroke [ Time Frame: Average of 6 years ]
    Time to first occurrence of fatal or disabling stroke
  • Mortality [ Time Frame: Average of 6 years ]
    Mortality
  • MACE [ Time Frame: Average of 6 years ]
    Major adverse cardiovascular events - CV death, non-fatal MI or non-fatal stroke
  • Physical function [ Time Frame: Average of 6 years ]
    Physical function as assessed by smRS
  • Change in SBP [ Time Frame: Average of 6 years ]
    Change in SBP
  • 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
  • Cognitive Impairment [ Time Frame: Average of 6 years ]
    Overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA)
  • Cognitive Impairment Supplement [ Time Frame: Average of 6 years ]
    Overall defined by standard cut-points with Brief Memory and Executive Test (BMET)
  • Medication Adherence [ Time Frame: Average of 6 years ]
    Self-reported measures, Pill counts
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial
Official Title  ICMJE Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Substudies: MRI, Cognitive
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Intracerebral Haemorrhage (ICH)
  • Hypertension
Intervention  ICMJE
  • 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
  • Drug: Placebo
    1 capsule taken orally once daily for average of 72 months
Study Arms  ICMJE
  • Experimental: Triple Pill (active treatment)
    telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;
    Intervention: Drug: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg
  • Placebo Comparator: Placebo
    received via blinded study capsules
    Intervention: Drug: Placebo
Publications * Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2. Erratum in: Lancet Neurol. 2021 Jun 9;:.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 24, 2020)
1500
Original Estimated Enrollment  ICMJE
 (submitted: March 2, 2016)
4200
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Grace Balicki +61 2 8052 4811 gbalicki@georgeinstitute.org.au
Contact: Ruth Freed +61 2 8052 4522 rfreed@georgeinstitute.org.au
Listed Location Countries  ICMJE Australia,   Brazil,   Georgia,   Netherlands,   Nigeria,   Singapore,   Sri Lanka,   Switzerland,   Taiwan,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02699645
Other Study ID Numbers  ICMJE TRIDENT-1103886
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: 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
Responsible Party The George Institute
Study Sponsor  ICMJE The George Institute
Collaborators  ICMJE The University of New South Wales
Investigators  ICMJE
Principal Investigator: Craig Anderson The George Institute
PRS Account The George Institute
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP