Hypertension, Intracerebral Haemorrhage (ICH)
Conditions
Keywords
Blood Pressure (BP), Stroke
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.
Interventions
DRUGtelmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg
1 pill taken orally once daily for average of 72 months
DRUGPlacebo
1 pill taken orally once daily for average of 72 months
Sponsors
The University of New South Wales
The George Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrent Stroke | Average of 6 years | Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ischaemic Stroke | Average of 6 years | Time to first occurrence of ischaemic stroke |
| Fatal or disabling stroke | Average of 6 years | Time to first occurrence of fatal or disabling stroke |
| Mortality | Average of 6 years | Mortality |
| MACE | Average of 6 years | Major adverse cardiovascular events - CV death, non-fatal MI or non-fatal stroke |
| Physical function | Average of 6 years | Physical function as assessed by smRS |
| Change in SBP | Average of 6 years | Change in SBP |
| HRQoL according to the EQ-5D-3L | Average of 6 years | Health-related quality of life according to the European Quality of Life 5-Dimensional Assessment, 3-Level version |
| Recurrent ICH | Average of 6 years | Time to first occurrence of recurrent ICH |
| Cognitive Impairment Supplement | Average of 6 years | Overall defined by standard cut-points with Brief Memory and Executive Test (BMET) together with assessments of functional impairment related to cognition defined by QDRS score and short form IQCODE, which will also allow subtyping of 'probable' or 'definite' dementia or mild cognitive impairment according to standard diagnostic criteria. |
| Depression | Average of 6 years | According to standard cut-point scores on the PHQ-9 |
| Cerebral small vessel disease | Average of 6 years | Defined by various standard markers on routine MRI, measured by individual components and overall CSVD burden. The primary measure of CSVD is FLAIR WMH volume. |
| Medication Adherence | Average of 6 years | Self-reported measures, pill counts |
| Safety in terms of Serious Adverse Events (SAEs) | Average of 6 years | SAEs |
| Tolerability in terms of Adverse Events of Special Interest (AESIs) | Average of 6 years | AESIs: Headache, Syncope/collapse, Falls, Pedal oedema/ankle swelling, Hypo/hyperkalaemia, Hyponatraemia |
| Cognitive Impairment | Average of 6 years | Overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA) |
Countries
Australia, Brazil, Georgia, Malaysia, Netherlands, Nigeria, Singapore, Sri Lanka, Taiwan, United Kingdom
Outcome results
None listed