Background and aims: Patients who suffer intracerebral haemorrhage (ICH) are at very high-risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimise secondary prevention. TRIDENT aims to determine the effects of a novel SPC ‘Triple Pill’, three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20mg, amlodipine 2.5mg, indapamide 1.25mg), with placebo, for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH.
Methods: An international, double-blind, placebo-controlled, randomised trial in adults with ICH and mild-moderate hypertension (systolic BP 130-160mmHg), who are not taking any Triple Pill component drug or equivalent at greater than half-dose. 1500 randomised patients will provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, disability, cognitive impairment/dementia, burden of cerebral small vessel disease on MRI and safety.
Results: Recruitment started 28 September 2017. Up to 15 May 2024, 1614 patients have been randomised at 55 active sites in 10 countries. Recruitment has been extended to increase the study power. Mean triple pill adherence after 36 months is 74%. Follow-up is expected to continue until mid-2025.
Conclusions: Low-dose Triple Pill BP lowering could improve long-term outcome after ICH.
Trial Registration: ClinicalTrials.gov (NCT02699645)
(N=246)