Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Substudies: MRI, Cognitive
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,671
- 试验地点
- 58
- 主要终点
- Recurrent Stroke
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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.
研究组 & 干预措施
Triple Pill (active treatment)
telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;
干预措施: telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg (Drug)
Placebo
Matched placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Recurrent Stroke
时间窗: Average of 6 years
Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.
次要结局
- Depression(Average of 6 years)
- Recurrent ICH(Average of 6 years)
- Ischaemic Stroke(Average of 6 years)
- HRQoL according to the EQ-5D-3L(Average of 6 years)
- Cognitive Impairment(Average of 6 years)
- Fatal or disabling stroke(Average of 6 years)
- Mortality(Average of 6 years)
- MACE(Average of 6 years)
- Physical function(Average of 6 years)
- Change in SBP(Average of 6 years)
- Cognitive Impairment Supplement(Average of 6 years)
- Cerebral small vessel disease(Average of 6 years)
- Medication Adherence(Average of 6 years)
- Safety in terms of Serious Adverse Events (SAEs)(Average of 6 years)
- Tolerability in terms of Adverse Events of Special Interest (AESIs)(Average of 6 years)