Oral Presentation Asia Pacific Stroke Conference 2024

Triple therapy prevention of recurrent intracerebral disease events trial (TRIDENT): progressive report (106989)

Craig Anderson 1 , Ruth Freed 1 , Natalie Espinosa 1 , Anthony Rodgers 1 , Asita De Silva 2 , Bimsara Senanayake 3 , Sheila O Martins 4 , Catharina JM Klijn 5 , Laurent Billot 1 , Qiang Li 1 , Hisatomi Arima 6 , Nguyen Huy Thang 7 , Wan Asyraf Wan Zaidi 8 , Tinatin Kherkheulidze 9 , Kolawole Wahab 10 , Urs Fischer 11 , Tsong-Hai Lee 12 , Christopher Chen 13 , Octavio Pontes-Neto 14 , Thompson Robinson 15 , Jiguang Wang 16 , Floris H Schreuder 5 , Richard I Lindley 1 , Mark Woodward 1 , Stephen McMahon 1 , Lili Song 1 , Rustam Al-Shahi Salman 17 , Clara K Chow 18 , John Chalmers 1
  1. The George Institute for Global Health, Camperdown, NEW SOUTH WALES, Australia
  2. Clinical Trials Unit, Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
  3. Institute of Neurology, National Hospital of Sri Lanka, Colombo, Sri Lanka
  4. Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil
  5. Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
  6. Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
  7. Stroke Unit, 115 Hospital, Ho Chi Minh city, Vietnam
  8. Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia
  9. Urgent Neurological Clinic Neurology, Tbilisi State Medical University, Tbilisi , Georgia
  10. Department of Medicine, University of Ilorin, Ilorin, Nigeria
  11. Department of Neurology , University Hospital Bern and University of Bern, Bern, Switzerland
  12. Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, Linkou, Taiwan
  13. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore,, Singapore
  14. Department of Neurosciences and Behavioural Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo,, Ribeirao Preto, Brazil
  15. College of Life Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, United Kingdom
  16. Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
  17. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
  18. Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Sydney, Australia

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)