None listed
Conditions
Brief summary
Acute intracerebral haemorrhage (ICH) is the most serious and least treatable form of stroke, accounting for at least 10% of the 20 million new strokes (including 50,000+ Australians) that occur in the world 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 BP of patients after ICH, such as from the PROGRESS trial undertaken by several of the applicants, many patients with ICH do not receive blood pressure lowering and if they do, receive treatment so that their BP is inadequately controlled. The aim of this study is to demonstrate the superiority 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 in a large-scale, international, double-blind, placebo-controlled, randomised controlled trial.
Interventions
Triple Pill (active treatment) - telmisartan 20mg, amlodipine 2.5mg and indapamide 1.25mg; taken orally, once daily until end of study.
The study is event-driven, with the average follow-up treatment period for participants being 3 years. The study will end after the required number of primary endpoints have been reported.
Medication adherence and accountability is monitored through self-reports of doses missed and pill counts at every visit until end of treatment.
Sponsors
The George Institute for Global Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Adults (greater than or equal to 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 [NHF] 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 o telmisartan 20 or 40mg, amlodipine 2.5 or 5mg, indapamide 1.25mg, or o an equivalent class (ARB, CCB or thiazide [TZ]-like diuretic), or o a beta-blocker (BB) • Contraindication to any of the study medications, in the context of currently prescribed BP-lowering medication Exclusion Criteria for MRI (as applies) • Any MRI contraindication (e.g. metallic implants, claustrophobia, etc) or participant refusal • 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)
Outcome results
None listed