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

The George Institute

Status and phase: Enrolling; Phase 3

Conditions: Hypertension; Intracerebral Haemorrhage (ICH)

Treatments: Drug: Placebo; Drug: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg

Study type: Interventional

Funder types: Other

Identifiers

NCT02699645

TRIDENT-1103886

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults (≥18 years) with a history 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 or 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)

Exclusion Criteria for MRI (as applies)

• Any MRI contraindication (e.g. metallic implants, claustrophobia, etc) or participant refusal.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,600 participants in 2 patient groups, including a placebo group

Triple Pill (active treatment)

Experimental group

Description:

telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;

Treatment:

Drug: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg

Placebo

Placebo Comparator group

Description:

Matched placebo

Treatment:

Drug: Placebo